Knowing that the car emperor has been on the line for 7 years, the valuation is 3 billion US dollars, which is close to the market value of car home

Author Pan Lei

Editor hai Yao

Tuyuan Midjourney

To be honest, you have to understand the car emperor.

This is the Slogan of ByteDance’s car information platform "Know the Car Emperor", which became popular in the early days by guiding car owners to publish their car experience. Now it is the top stream of car vertical content platforms, with two trump cards: short video and live broadcast.

According to some data, Knowing Car Emperor has been the largest car live broadcast platform in China as early as almost four years ago.

Investors are also concerned about the money-making opportunities brought about by the subversion of the old vertical websites of cars by Know Car Emperor-such as car home and Easy Car, all of which have been listed in the US stock market.

The latest news shows that investment institutions, including Sequoia China, KKR and General Atlantic, are ready to provide up to $800 million for Chedi to support its IPO.

General China of Sequoia invested in this round of financing, and contributed $400-500 million.

This makes the valuation of the car emperor as high as $3 billion.

Considering that the car emperor App has been online for less than 7 years, this is an amazing valuation explosion.

In contrast, the market value of car home currently listed on NYSE is about $3.5 billion.

This is also in line with the iterative law of automobile information websites-every time a new automobile information giant appears, it basically means a cruel reshuffle.

According to Byte insiders, the number of daily users who know Chedi began in October 2021, and has already surpassed car home and Easy Car.

This also makes it logical for investors to throw a lot of money in pursuit of understanding the car emperor.

From "auto channel" to the number one in the industry

Understand the prototype of the car emperor is ByteDance’s "today’s headlines" auto channel, which is actually closer to auto channel in the early portal era.

It is said that in August 2017, after being hatched by the commercialization department of ByteDance, it was officially launched to understand Chedi App.

Backed by the huge "flow pool" of today’s headlines, the number of users who know the car emperor is growing rapidly.

According to the "Autumn Report 2017" released by the mobile Internet data organization "QuestMobile" in October of that year, only two months after the launch of Chedi App, active user data has already ranked among the TOP5 in the industry.

At that time, car home ranked first, with 17.37 million active users, while Car Master ranked fifth with 1.28 million users.

From then on, it took only four years, and car home, who has been the industry leader for many years, was trampled under his feet.

This kind of overspeed development obviously makes Byte interested in splitting up the car emperor.

At the beginning of 2023, it was reported that Byte moved the employees who knew the car emperor to a newly established wholly-owned subsidiary.

In addition, it is said that employees who know Chedi have independent office space.

This makes the outside world believe that Byte may be preparing for the introduction of external shareholders until the spin-off and listing.

According to the information provided by the third-party enterprise inquiry agency, on December 21, 2023, the corporate legal person who knows the car emperor changed from today’s headline to "Xiamen Know Car Technology Co., Ltd.".

This shows that Master Che officially became independent from ByteDance.

According to the data, the major shareholder of Xiamen Zhiche is He Jian (holding 60% of the shares), who also serves as the president of Zhiche Di.

Until now, it has exploded to seek financing with a valuation of $3 billion, indicating that knowing the car emperor is one step closer to the final IPO.

Seize the short video outlet

"We really want to vote for you. After all, newspapers have been very supportive of our work in communication for so many years, but unfortunately, customers have not given any budget to the print media at all."

This is the feedback from a senior official of a newspaper in Beijing who personally led a team to visit 4A Company more than ten years ago.

4A company said that the customers of car companies gave most of the budget to the online portal, leaving no budget for the print media including newspapers, which also made it impossible to complete the delivery.

This 4A company’s attitude towards seeking advertising cooperation with newspapers is a microcosm of several major portals, such as Sohu, Sina, Tencent, Netease and Phoenix, which became the mainstream automotive information platform at that time.

The "auto channel" of these websites, with large traffic, fast communication speed and various forms (there have been some test drive videos), completely subverts the information dissemination mode in the era of print media, and also makes it difficult for traditional print media to obtain business cooperation opportunities.

In the era when the portal website auto channel is booming, employees are busy.

A person who once worked as a "car editor" in a portal website said that he had been on a business trip for several weeks and participated in various test drives and release activities organized by car companies. "I had to ask my wife to send my change of clothes to the airport, and I changed my clothes and flew to the next destination."

However, almost at the same time as the popularity of the portal website auto channel, automobile vertical websites are sought after by more and more users because they can provide more focused and professional content.

In 2000, Easy Car was founded, and car home was founded five years later.

The establishment of these two representative websites indicates the arrival of the era of traffic segmentation.

In other words, these two websites can provide more professional content, and users are more accurate and more valuable to car companies.

So the balance of traffic began to gradually shift to such vertical websites as Easy Car and car home.

Auto channel, a web portal, was subverted by car home and Easy Car.

From the establishment of car home in 2005 to the launch of Know Car Emperor APP in 2017, it can basically be regarded as the golden age of car home and Easy Car.

In 2017, car home’s net revenue was 6.2102 billion yuan, up 4.2% year-on-year, and its net profit reached 2.0016 billion yuan, up 63.0% year-on-year.

Another vertical website giant, Easy Car, earned RMB 8.751 billion in the same year, up 51.6% year-on-year, and its gross profit for the whole year was RMB 5.517 billion, up 49.3% year-on-year.

Car home’s forum is an epoch-making product form, which provides a platform for car owners to communicate and interact.

This also shows that the content produced by users is becoming the value core of the automobile information platform.

When the mobile Internet emerged, after the car-savvy emperor exploded in the form of short video of UGC (User Generated Content), he was caught off guard by car home and Easy Car-the latter two are basically products of the PC era.

In fact, almost no forum products in the automotive field have been successfully copied to the mobile platform.

Understand that the car emperor has done this through short video outlets.

This makes it the latest subversive of automobile information platform.

At present, auto channel, the portal website, has basically lost its influence, and even car home has experienced a slowdown in business growth-the annual revenue in 2023 was 7.18 billion yuan, up 3.5% year-on-year, and the adjusted net profit was 2.159 billion yuan, down slightly year-on-year.

Knowing that Chedi has not announced specific revenue, it continues to make great strides in user growth.

In October, 2023, according to QuestMobile’s data, the daily growth rate of Knowing Car Emperor reached 57% in the past two years.

This may be related to the "empowerment" of today’s headlines-the automotive content published by users on today’s headlines will be automatically synchronized to the car-savvy emperor.

"online celebrity" is shaking the financial resources of knowing the car emperor

Corresponding to the iteration of automobile information platform, the relationship between it and automobile enterprises (dealers) has also experienced the change from cooperation to game.

In the early days of the portal, the cooperation between car companies and "auto channel" was mostly advertising and activity cooperation (various car forums or summits).

However, with the growing influence of the portal, its commercial value in new car sales leads began to stand out.

In other words, if you bring the address or contact information of the 4S store at the bottom of auto channel’s article, you can "drain" the relevant stores.

This may be the earliest way of selling "sales leads" about the automobile information platform.

However, it is Easy Car and car home that really carry forward this business model.

The reason is that they have more accurate traffic than portals.

Based on this, these vertical websites began to build professional products around sales leads.

More than a decade ago, the sales lead products promoted by automobile vertical websites to 4S stores were as high as hundreds of pages, detailing all the details such as clue acquisition and transformation.

This is also the biggest financial resource for car home and other vertical websites.

According to car home’s 2023 annual report, the number of cooperative dealers in that year exceeded 26,000.

In Q1 this year, car home’s clue service revenue was 726 million yuan, accounting for 45.1% of the total revenue of 1.609 billion yuan, exceeding media revenue (327 million yuan) and online marketing and other income (555 million yuan).

Now I understand that after Che Di became the traffic king of the automobile information platform, he also "inherited" the clue business model.

The bridge section of "the boy who kills the dragon will eventually become a dragon" is staged in this cycle, and the car emperor has become the latest "boy who kills the dragon".

However, the effectiveness of this business model is increasingly questioned by car companies.

At the beginning of this year, brands such as Wenjie and Zhijie under Huawei HarmonyOS Zhixing stopped "cooperating with members who know Car Emperor, car home and Easy Car".

This kind of recharge "member" is actually a sales lead product.

According to statistics, the annual membership fees of Easy Car and car home sold to dealers in 2024 both exceeded 200,000 yuan.

In 2019, due to the 20% increase in the membership fee of car home, many automobile dealer groups including Express Group and Zhongsheng Group suspended their cooperation, and the market value of car home once evaporated by 1.8 billion US dollars.

At that time, Li Hong, the president of Express Group, said through social media that "when a vertical website started from a car dealer was growing, it actually wanted to rely on monopoly to encroach on food", aiming at car home.

In 2023, Knowing Car Emperor upgraded the cooperation mode of members to CPS mode (Cost Per Sales), which triggered the anxiety of dealers.

Some dealers believe that this settlement mode leads to uncontrollable budget and refuses to cooperate.

After learning about Che Di, he released a letter to the dealers’ partners, saying that it was necessary to provide subsidies for dealers and reduce the burden on the industry, and this matter gradually subsided.

The suspension of cooperation between HarmonyOS Zhixing and the automobile vertical platform highlights the expensive nature of clue fees.

Some car companies or brands that implement the direct sales model even spend huge sums of money to build a clue acquisition and transformation system.

A few years ago, a brand of new power hatched by a car company in the north once spent tens of millions of yuan to build a clue system directly facing users according to the characteristics of the company.

The original intention of this system is not to "understand the car emperor", but to provide differentiated experience by directly serving users.

But in the objective effect, this model is equivalent to getting rid of the clues of the automobile information platform.

Moreover, as the cost of clues becomes more and more expensive, it also makes related car companies overwhelmed.

Recently, at the Guangdong-Hong Kong-Macao Auto Show, Yu Chengdong, managing director of Huawei, said that it was related to saving marketing expenses when talking about the creation of personal IP by car CEO.

Other car companies have also confirmed that this model can indeed bring about transformation.

According to Zhang Yong, CEO of Nezha, since the listing of Nezha L, the demand for orders has been in short supply, and "half of the credit is attributed to Lao Zhou"-Lao Zhou is Zhou Hongyi, which recently triggered the internet craze by criticizing Zhang Yong, promoting Nezha Automobile to learn from Lei Jun, and promoting Nezha Automobile to change its name, which also proved that the "online celebrity" effect can indeed be transformed into sales leads.

This makes the "clue" value of the automobile information platform represented by knowing the car emperor decline.

In addition, even "I really have to understand the car emperor" is being questioned.

At the end of 2023, the "2023 Winter Test of Knowing Car Emperor" released by Knowing Car Emperor showed that the endurance achievement rate of the extended range version of the M7 was only 31.6% in severe cold conditions, ranking first from the bottom among all test models.

Yu Chengdong said that this is "cheat people’s test, misleading people!"

Geely and Great Wall also questioned the test results of Che Di.

Relevant car companies said that the test of knowing the car emperor was warmed up for a long time before departure, which consumed a lot of electricity and did not conform to the real use scenario of users.

According to some data, the relevant evaluation of knowing the car emperor has been questioned for many times.

This erodes the content advantage of knowing the car emperor.

However, the status of the first traffic platform in the automobile circle, the valuation of up to $3 billion, and the financing of up to $800 million show that at least before the official listing of the capital market, knowing the car is attractive enough for investors.

Interpretation of ＂New Infrastructure＂ from the Perspective of Experts and How Blockchain Empowers Digital Economy

　　People’s Daily Online, Beijing, May 29 (Reporter Qiao Xuefeng, intern Jin Yusi) During the two sessions, People’s Daily launched a special program "Cloud Living Room of the two sessions", inviting NPC deputies and CPPCC members to meet with netizens on the "Cloud" to discuss hot topics.

　　How can new infrastructure help the modernization of government governance capacity and the high-quality development of digital economy? How does the blockchain empower new infrastructure? On May 28th, the "New Infrastructure Moment" was held in the cloud living room of the NPC and CPPCC, inviting delegates, local government leaders, experts and scholars, and representatives of outstanding enterprises in new infrastructure to talk about new infrastructure.

　　"We have moved from the traditional economy to the digital economy, and the digital economy will move from the lives of our people to the entire social and industrial field." Wang Xiaochuan, member of Chinese People’s Political Consultative Conference and CEO of sogou Company, said that with the development of artificial intelligence technology, machines have begun to have more technologies to imitate people’s expressions, looks or voices, and this technology can already replace the anchors of some programs. This aspect will also arouse public concern, and it is suggested that the illegal use of these technologies can be guided or restricted by legislation, which can make the industry develop better.

　　Wang Xiaochuan pointed out that artificial intelligence must form industrial synergy and application scenarios. The developed Internet industry in China has laid a good foundation for the development of artificial intelligence, but the core technology of artificial intelligence chips is still in western countries. We need to develop this technology to make artificial intelligence achieve comprehensive and stable development.

　　In view of the problem that blockchain technology helps the government’s digital governance, Feng Kui, deputy director of the Central Economic Committee of the NLD and a researcher at the Research Center for the Reform and Development of Cities and Small Towns in China, took the development plan of the Yangtze River Economic Belt and the Chengdu-Chongqing Twin-city Economic Circle as examples, and pointed out that blockchain technology can play five major roles in solving the problems of diversification and data decentralization in new spaces: "First, promote the formation of interest communities in new spaces through consensus mechanism. The second is to create transparent and trustworthy application scenarios through smart contracts. The third is to build a joint and collaborative decision-making mechanism through data sharing. The fourth is to improve the efficiency of government business by optimizing the government service process. The fifth is to improve the efficiency of market-oriented allocation by promoting the flow of factors. "

　　In addition, the application of digital governance in the "new infrastructure" era during the COVID-19 epidemic also showed its advantages of convenience and efficiency. Dong Xuegeng, director of the Big Data Administration of Hainan Province, said that up to now, the coverage rate of Health One Code in Hainan Province has reached 124%. The construction of epidemic prevention and control big data system not only makes the health code cover all the people in the province, but also ensures that migrant workers and tourists can also receive the code, which helps Hainan Province to achieve the two requirements of external input and internal non-proliferation.

　　The advantages of "new infrastructure" are obvious to all, and the development status of blockchain technology and new infrastructure, He Yifan, general manager of Beijing Jujube Technology Co., Ltd. made an answer in the program. He said: "Blockchain technology is a very new technology. At present, our country is basically on the same starting line as other countries, and the positioning of the blockchain service network is global. It is a global new infrastructure that can serve the world and developers all over the world."

　　Wang Zhen, general manager of Digital City Company of China Xiong ‘an Group, said that the characteristics of blockchain’s safety, credibility, openness and cooperation contributed to its integration with the "new infrastructure" of digitalization, internetization and Internet of Things.

　　Wang Zhen pointed out that blockchain technology can make ‘ New infrastructure ’ The data flow in the data center is moving, so that more people can participate in urban computing. At the same time, the digital currency gene of blockchain technology enables it to promote the development of "new infrastructure" in terms of operation management, financing and derivative finance by means of asset digitization.

　　Talking about the international competitiveness of China’s "new infrastructure" technology, Ma Jun, co-founder and partner of Tongdun Technology, pointed out that all the fields involved in the new infrastructure are high-tech frontier technologies, and the autonomy and controllability of China’s core technology must be maintained, and will become a necessary measure for the country’s high-quality development in the future.

　　At the same time, Ma Jun Drive suggested: "The future construction of new infrastructure is not only to build hard infrastructure, but also to build soft infrastructure. Only by combining soft and hard and inserting the wings of intelligent software into the hardware can the new infrastructure play a better role."

　　He Yifan, Ma Jun Drive and other representatives of new infrastructure enterprises summed up the international competitiveness and progress direction of China’s new infrastructure through the experience accumulated in the stage of technological exploration. Zhu Keli, Executive Dean of National Research Institute of New Economy, once again analyzed the relationship and prospect between "new infrastructure" and "new economy" from the perspective of long-term economic impact.

　　"New consumption and new infrastructure are two issues that have attracted much attention at present, and they shoulder the heavy responsibility of reviving China’s economy in the post-epidemic context." Zhu Keli said that a digital bridge between new infrastructure and new consumption is being formed historically, and the new economic logic of industrial interconnection and the digital platform make it possible for new infrastructure and new consumption to resonate at the same frequency.

　　Zhu Keli pointed out that the relationship between the new economy and the new infrastructure is that the new infrastructure provides an effective operating basis for the development of the new economy. As a large system, the new economy can also provide good technical support, long-term operating mechanism and broad development soil for new infrastructure.

　　Speaking of new infrastructure and digital economy, Geng Zhijun, vice president of Tencent, also pointed out that code economy is a new way of connection, which can gradually transfer the business model in the traditional economic society to the online. During the whole epidemic period, the relationship generated by code will become more and more obvious and more and more. "Of course, the code economy does not necessarily refer to an economy that simply links through QR codes. We are more talking about a mapping between the real world and the virtual world, or a connection between the real world and the virtual world, resulting in more economic development."

　　Yan Zhijun also said that it is not difficult to see from this epidemic that online and offline integration will enhance the resilience of more market players, thus boosting the digital transformation of small and medium-sized enterprises. In other words, good use of coupons can cultivate future customers of new consumption and new infrastructure, and the two will organically connect the enterprise and the government through digitalization.

How to ＂eat＂ resistance？ Nutrition expert： three meals a day, four kinds of food.

　　BEIJING, Beijing, Feb. 23 (Reporter Sun Zifa) On Feb. 23, the lunar calendar has entered the Year of the Rat in February, and the "epidemic" of the whole country has continued for more than a month. At the moment of epidemic situation, it is very important for the public to do personal protection, improve their own resistance and strengthen their immunity.

　　As the saying goes, people are iron rice and steel. What is the connection between diet and immunity? During the "epidemic" war, how to enhance the body’s immunity through diet? What problems should be paid attention to in diet? Chief physician Chen Wei, chairman of the Clinical Nutrition Branch of China Nutrition Society and deputy director of the Clinical Nutrition Department of China Academy of Medical Sciences/Peking Union Medical College Hospital, responded one by one through the online interview organized by China Association for Science and Technology, stressing that three meals a day should be kept healthy, four kinds of food should be guaranteed every day, more than 12 kinds of food should be guaranteed every day, and at least 25 kinds of food should be eaten every week.

　　Professor Bo Huang, vice chairman of the Chinese Society of Immunology and the Department of Immunology of China Academy of Medical Sciences/Peking Union Medical College, also pointed out that a healthy and reasonable diet is undoubtedly the basis for maintaining the normal function of the whole cell. In the face of the current epidemic situation, eating more foods such as mushrooms, Lycium barbarum, Ganoderma lucidum powder and auricularia auricula is helpful to improve immunity, because these foods are rich in plant polysaccharides, including lentinan, Lycium barbarum polysaccharide and Ganoderma lucidum polysaccharide, which can stimulate receptor molecules on the surface of natural immune cells and make immune cells in a pre-stimulated state.

　　What is the relationship between diet and immunity?

　　Chen Wei said that the human body has three layers of "defense walls" to resist external invasion. The first layer is skin and mucous membranes on the surface of the body, through which more than 90% of viruses and bacteria are attacked by the outside world. If the virus enters the body, the body will start the second layer of protection, which can kill most foreign viruses and germs by secreting mucus and phagocytizing cells through the mucosa; If it is unfortunate that some viruses enter the body or even cells, the third layer of human protection will start, and antibodies will be produced by intracellular substances, and the invading viruses will be removed through antibodies. Therefore, these three lines of defense determine the vast majority of people’s immune functions.

　　Are these three layers of defense related to diet? Chen Wei pointed out that the mucus secreted by mucous membranes mentioned above and the antibodies produced by human own cells are all protein, and these protein forms the basis of the body’s resistance. "Where does protein come from? You have to eat to come. Unlike plants, the human body needs light for photosynthesis, and the human body must rely on our mouth to eat nutrients and eat our resistance. "

　　How to "eat" immunity?

　　Since diet is closely related to resistance, how to improve resistance and enhance immunity through diet? Chen Wei gave the answer with a set of data:

　　First, keep healthy three meals a day. During the epidemic, many people are forced to stay at home and keep a regular life. In addition to normal sleep, they must eat three meals to maintain their resistance, and they must not reduce their meals, including breakfast, lunch and dinner. Second, four kinds of food should be guaranteed every day, including grains (sweet potatoes), vegetables and fruits, high-quality protein foods and oils; The third is to ensure more than 12 kinds of food every day, that is, there must be at least 12 kinds of food in the four categories; Fourth, eat at least 25 kinds of food a week to achieve a more balanced nutrition and enhance resistance.

　　He also provided specific recipes, saying that grains (sweet potatoes) should eat at least three or more staple foods and no more than one kilogram every day, with flour and rice or coarse grains, including rice, white flour and other ingredients, and some sweet potatoes like sweet potatoes, yams, taro, potatoes and other ingredients; Vegetables and fruits should eat 1-2 kg every day to supplement vitamins and dietary fiber to meet the basic needs of nutrition; High-quality protein foods "should eat good things in place", including meat, eggs, milk and bean products. Among them, at least 2-3 pieces of meat, 1-2 eggs, 1-2 bags of milk and a little tofu every day constitute a high-quality protein combination; Oil should be protected with a little oil, 2-3 spoonfuls of oil every day.

　　What should you pay attention to during the epidemic?

　　Chen Wei first clarified the rumor that "eating garlic can prevent viruses" and "rubbing sesame oil can fight germs" and other foods to treat COVID-19. He pointed out that the impact of food on immunity only refers to the basic role, and there is no special food, and folk remedies can’t cure diseases, nor can they really prevent diseases. "Eating a good meal, doing exercise and doing personal protection are the most important and effective ways to get through the epidemic safely".

　　He said that during the epidemic period, the public’s attention in diet also included sharing meals, cooking food thoroughly, not superstitious about refrigerators and balconies, and staying away from wild animals.

　　In the dining system, everyone will be very careful when going out or in public, but they will often relax when they get home. We should pay attention to this. We should reduce family dinners, and three people should eat their own meals. If there are public dishes, we must try our best to use public spoons and chopsticks to reduce cross-correlation.

　　When cooking food, we must pay attention to cooking the food thoroughly. Chen Wei suggested heating it for one minute more than usual during the epidemic. "It is cooked, cook it for one more minute and stew it for one more minute, which is safe for you and your family life."

　　It’s still winter, and some people in the north want to put food such as fruits and vegetables on the balcony, which can’t be cold outside, or put it in the refrigerator, which can freeze the germs to death. Chen Wei pointed out that those who have this idea must pay attention to the fact that refrigerators and balconies can only provide a certain storage temperature, and the temperature difference between day and night will also change greatly. Generally speaking, 0 -4 degrees can not inhibit the growth of bacteria. In addition, homebodies, in particular, should change stale ingredients regularly, and if they find a little bad fruits and vegetables, they should be removed as much as possible.

　　From the aspect of staying away from wild animals, at present, the epidemic situation is very related to wild animals, and all kinds of wild animals (food) should be rejected. Of course, there is no need to overdo it. During the epidemic prevention and control period, many people killed and threw pets out of fear, so it is unnecessary. After thousands of years of domestication, human beings can also rest assured of eating meat products of livestock and poultry such as pigs, cattle, sheep, chickens and ducks.

　　Chen Wei also specially reminded that in response to epidemic prevention and control, the public must reduce the damage to their own resistance in their diet, including avoiding eating too much unclean food that is easy to upset their stomachs, and paying attention to separating raw food from cooked food and tableware, so as to reduce the disease caused by dietary factors. It brings new burdens to individual resistance.

Heavy surprise! ＂Men in Black： Global Pursuit＂ is the creator of Dragon Boat Festival in China.

1905 movie network news Hollywood sci-fi action giant jointly produced by Columbia Pictures and Tencent Pictures released China Special Action — — The film’s main creator is coming to China on the Dragon Boat Festival, and the lineup is unprecedented and luxurious. The two leading actors, Chris Hemsworth and tessa thompson, and the director F Gary Gray, are the first to combine into a film publicity platform.

A few days ago, the film officially launched global publicity, and the first red carpet fan activity held in Bali was even more climax, which made domestic fans envious.

　

Fairy group is about to airborne Beijing elite agents to start China special operation

"Men in Black: The Global Pursuit" has been highly anticipated by fans since its inception. As the hottest powerful actors in Hollywood today, "Brother Hammer" Chris Hemsworth and "Valkyria" tessa thompson have a high popularity in China, and a large number of fans are eager for idols to come to China. The two collaborated again after several Marvel Universe super-British blockbusters, and H&M, an elite agent, showed remarkable tacit understanding in the new series of Men in Black. This is the first time that the golden partner of the "God of Heaven" and Super 8 director F Gary Gray have joined forces during the film promotion period to jointly "perform special tasks" in China. Brother Hammer, Chris shared the news of his visit to China with China fans in the form of a video letter for the first time, and warmly looked forward to spending the Dragon Boat Festival with you. It is reported that tessa thompson, the heroine of the film, and F Gary Gray, the director, both came to China for the first time to promote the film works. This heavyweight lineup gathered in Beijing to reveal the wonderful stories behind the scenes of the film to the audience.

　

Shooting interesting things, endless high-energy warning of aliens

In the new preview released at the same time as the news of coming to China, it shows that the film incorporates a lot of sci-fi actions and humorous elements. The thrilling action scenes and the high-energy weapons of future technology make people’s hearts beat faster and ignite. In particular, the super sports car with "one button to heaven" surprise operation hides a lot of heavy firepower equipment, which is worthy of being the exclusive car of top agents! Meng Xing Bing Bing also stole the show again. In the trailer, it was trapped in a glass bottle, but it used a secret weapon to draw a humanoid door frame in the bottle. Even Agent H and Agent M were dumbfounded by the unusual move.

　

Earlier, Chris Hemsworth revealed in an interview, "I am very happy to participate in the filming of" Men in Black: Global Pursuit ".There are many action scenes in it that test people very much, and it is also very interesting to shoot around the world with the crew." In the movie, agent H&M will travel around the world to hunt down evil aliens, and high-energy clips emerge one after another, which is worth looking forward to. On June 14th, the most exciting sci-fi action masterpiece in the summer file will be released soon.

　

The film Men in Black: The Global Pursuit is produced by Steven Allan Spielberg (,), directed by F Gary Gray (,), and co-starred by Chris Hemsworth (,), tessa thompson (,), liam neeson (series,), emma thompson (,Love Actually) and Rebecca Ferguson (,).


Five kinds of minor criminal cases in Shanxi Province can be reconciled.

　　　　On September 1st, the Provisions of Taiyuan People’s Procuratorate on the Application of Criminal Reconciliation in Handling Minor Criminal Cases (Trial) came into effect.


　　　　Set the original intention, resolve social contradictions and save judicial resources


　　　　Zhang, a middle school student in Xinghualing District, Taiyuan City, stabbed a person seriously in 2006. After accepting the case, the Xinghualing District People’s Procuratorate visited the victim and his relatives, and went to Zhang’s school to make a detailed study of his daily life. The procuratorate learned that Zhang is usually very dutiful, and although his academic performance is not very good, he has been rising steadily. Li, who was three years older than him before the incident, was bullied many times. After the parents learned about it, they took Zhang to the Li family to discuss the argument. However, Li was abusive to Zhang’s parents. Zhang was angry for a while and smashed Li into a serious injury. The two parties reached an agreement on civil compensation, and the Xinghualing District People’s Procuratorate finally made a decision not to prosecute.


　　　　This case has become a typical case encountered by Taiyuan People’s Procuratorate in the exploration of criminal reconciliation system.


　　　　"Such a child, just a moment of anger made an excessive move, subjective malignancy is very small. If he is sent to prison, his future life may be completely changed, and some teenagers will be’ infected’ again after being imprisoned, and they will completely embark on a wrong path. " Nan Li Ming Dow, Director of Public Prosecution Division I of Taiyuan Procuratorate, explained the original intention of the criminal reconciliation system.


　　　　The "Regulations" determine that in the process of minor criminal cases, the criminal suspect can actively gain the understanding of the victim by pleading guilty, apologizing, financial compensation, etc., and reach a criminal settlement agreement with the victim. After confirmation by the procuratorial organ, the procuratorial organ will make a decision not to prosecute the criminal suspect.


　　　　According to reports, in reality, if criminal sanctions are imposed on a large number of cases, under the existing judicial mechanism, both the offender and the victim are in a situation of mutual loss for a long time. For example, neighbors’ relationship, because one side’s head is broken and one side’s nose is interrupted at a moment’s quarrel, constitutes a minor injury. After the implementation of criminal sanctions, neighbors may die of old age, but it will increase social contradictions.


　　　　"Frankly speaking, prosecuting all these cases will not only have a bad social effect, but also waste judicial resources. Regardless of whether the case is big or small and involves prosecution, all procedures are actually exactly the same. The whole procedure has to be taken once. " A prosecutor said.


　　　　It is reported that from 2005 to 2006, Taiyuan City prosecuted 5,806 criminal cases with 9,223 people, among which 1,912 cases with 2,622 people were sentenced to fixed-term imprisonment of less than three years, accounting for 28% of the total number. There is considerable room for criminal reconciliation.


　　　　Experts analyze the theoretical basis of criminal reconciliation


　　　　According to Li Qi, an associate professor of Shanxi University Law School, criminal reconciliation has its profound theoretical basis.


　　　　First of all, criminal reconciliation is the requirement of implementing the criminal policy of combining leniency with severity. There are various criminal cases, and the circumstances of the crime are light and heavy, which requires different resolution mechanisms for cases of different nature, so as to make the strictness strict and the leniency lenient. For those minor cases, the application of criminal reconciliation instead of blindly emphasizing the investigation of criminal responsibility can not only eliminate the opposing feelings of both parties, protect the rights and interests of the victims, urge the perpetrators to confess their sins and mend their ways, turn negative factors into positive ones, but also save judicial resources.


　　　　Secondly, criminal reconciliation embodies the characteristics of China traditional culture. In the traditional culture of China, there is a spirit of "harmony is the most important". Reconciliation based on distinguishing right from wrong and consultation between the two sides is conducive to social stability.


　　　　Thirdly, criminal reconciliation adapts to the trend of restorative justice in the international community. The focus of restorative justice is not the pursuit of punishment for crimes, but the pursuit of order reconstruction and social harmony. Procedurally, restorative justice also pays more attention to consultation and reconciliation. From the practical point of view, restorative justice has become a rising judicial reform movement in the international scope, and has also achieved remarkable results in preventing crimes, reducing judicial investment and safeguarding the interests of victims.


　　　　Finally, criminal reconciliation is in line with the spirit of China’s current laws. China’s criminal law, criminal procedure law, etc., have some provisions on non-penalty punishment methods, mediation and reconciliation for minor cases. However, due to the lack of detailed legal provisions, the scope of application of these provisions and procedures has been greatly limited, and the positive functions have not been fully exerted. Therefore, it is very necessary to improve and refine the operating procedures.


　　　　Scope of application Five kinds of minor criminal cases


　　　　According to the "Provisions on the Application of Criminal Reconciliation in Handling Minor Criminal Cases (Trial)" promulgated by Taiyuan Municipal People’s Procuratorate, criminal reconciliation is applicable to minor criminal cases that meet one of the following circumstances: (1) The criminal suspect has a statutory lighter, mitigated or exempted punishment; (2) The criminal suspect is a negligent offender, a first-time offender or an occasional offender; (3) The criminal suspect is a minor, an elderly person or a student at school; (4) The victim is obviously at fault; (five) the case is caused by disputes between relatives and friends, neighbors, colleagues or classmates.


　　　　In practice, criminal reconciliation can easily cause people’s worries about "buying punishment with money". In this regard, the head of the criminal reconciliation research group explained that although criminal reconciliation pays attention to protecting the interests of victims, criminal suspects, the state and society also benefit from it. Through criminal reconciliation, victims can be prevented from retaliating against criminal suspects and criminal suspects can be prevented from endangering society again, which not only embodies the protection of human rights, but also plays a positive role in controlling the occurrence of social crimes. Therefore, criminal reconciliation is a judicial idea and model to prevent crime from the victim’s point of view, which embodies humanistic care and social civilization and progress, and should not be misunderstood as "buying punishment with money".


　　　　In addition, in criminal reconciliation, the "power" of procuratorial organs is remarkable. In this regard, the person in charge of the research group introduced that the procuratorial organ is a legal supervision organ. If the criminal suspect and the victim reach a settlement, they shall apply to the procuratorial organ for confirmation. The procuratorial organ is not the host of criminal reconciliation, but the supervisor of criminal reconciliation. In practice, we should try to avoid the interference of "public power" on the will of both parties.


　　　　Procuratorial organs also have corresponding supervision and restriction mechanisms in the application of criminal reconciliation. If the grass-roots procuratorial organ intends to make a decision not to prosecute by applying criminal reconciliation to minor criminal cases, it shall be discussed and decided by the procuratorial Committee and reported to the Taiyuan Municipal People’s Procuratorate for approval; After accepting the request from the grass-roots procuratorial organs, the Taiyuan Municipal People’s Procuratorate shall report it to the procurator-general for decision or the procurator-general shall submit it to the procuratorial committee for discussion and decision.


　　　　Link:


　　　　● What are the conditions for the procuratorial organ to confirm that the parties have settled?


　　　　If the settlement agreement meets the following conditions at the same time, the procuratorial organ shall confirm that the criminal suspect and the victim have reconciled: (1) The criminal suspect pleads guilty and repents, apologizes to the victim, and makes corresponding commitments in writing; (2) The criminal suspect and the victim have reached a consensus on civil compensation matters, which have been fully fulfilled; (3) The victim expresses forgiveness for the criminal suspect.


　　　　● What happens when the procuratorate does not confirm that the parties have settled?


　　　　If the settlement agreement has one of the following circumstances, the procuratorial organ shall not confirm it: (1) it infringes on the national interests, social public interests and the legitimate interests of other citizens; (two) against the true meaning of the parties; (3) Violating the prohibitive provisions of laws and administrative regulations.


　　　　● What corresponding supporting measures does the procuratorial organ have after criminal reconciliation and non-prosecution?


　　　　Within one year after the implementation of the decision not to prosecute, the person who is not prosecuted shall regularly report to the procuratorial organ in writing his compliance with laws and regulations and his commitment. The procuratorial organ shall pay a return visit to the person who is not prosecuted and the victim. (Reporter Yuan Wei)


Editor: Wang Yuxi

Don’t be careless, these symptoms may be cancer signals.

　　In the face of cancer, everyone often talks about cancer discoloration.

　　The source of this fear is not groundless. In recent 40 years, the cancer burden in China has also increased significantly.

　　According to an article published in The Lancet Oncology by He Jie, an academician of China Academy of Sciences, in the past 40 years, the proportion of people in China who died of cancer has decreased from 1973— The proportion of cancer increased from 10.1% in 1975 to 24.2% in 2015, and the burden of cancer increased day by day.

　　Why are some cancers found late?

　　Some cancers are terminal as soon as they are discovered. Why?

　　First, the concealment of cancer itself is high. The incubation period of most cancers is long, which is very long, whether it is from oncogene mutation or from persistent infection with carcinogenic virus to the final formation of cancer. In this process, there may be no obvious clinical symptoms, which are not easy for patients to detect. Once there are perceptible clinical symptoms, they often metastasize, which is the advanced stage of cancer.

　　Second, patients are too negligent. Some cancers have nonspecific symptoms in the early stage, such as fatigue, cough, slight chest pain or abdominal pain, but many patients often neglect diagnosis and treatment, or the abnormal indicators of physical examination do not further clarify the cause, which delays the treatment opportunity.

　　Third, there is no regular physical examination. Many people feel healthy and refuse to have regular health checkups, but they don’t know that health checkups can find some cancers in time.

　　So which cancers are advanced as soon as they are discovered?

　　Pancreatic cancer is often called the king of cancer, and its survival rate is low. Most of the early pancreatic cancer has no clinical symptoms, and it is in the middle and late stage when it is diagnosed, so it is difficult to cure.

　　The incidence and mortality of lung cancer have increased the fastest, and it is one of the most threatening malignant tumors to people’s health and life. The symptoms of early lung cancer are often mild, and there may even be no discomfort.

　　The symptoms of early liver cancer generally have no obvious characteristics, and the middle and late stages will be accompanied by symptoms such as liver pain, abdominal distension, fatigue and emaciation.

　　These symptoms require vigilance.

　　British scholars published an article in The Lancet Oncology. By studying the data of 8,000 patients suffering from 12 common cancers, it was found that 13 of the 20 symptoms appeared in the early stage of cancer, including abnormal nevus, breast mass, postmenopausal bleeding, rectal bleeding, lower urinary tract symptoms, hematuria, change of defecation habits, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss and so on. Therefore, once the above symptoms appear, ordinary people should see a doctor in time.

　　It needs to be emphasized that we should pay special attention to weight loss. A study published by Oxford University in the British Medical Journal on August 13th, 2020 shows that subjects who suddenly lose weight are twice as likely to develop cancer as those who don’t.

　　How do ordinary people avoid getting sick

　　Doing the following will help us stay away from cancer.

　　In daily life, people need to pay attention to stay away from ionization and ultraviolet radiation.

　　Develop a reasonable dietary structure and balanced nutrition. Control the intake of red meat food, choose rough grains, and increase the intake of fresh fruits and vegetables and low-calorie foods.

　　Keep moving properly. Adults should try to reduce sedentary time, and exercise time is recommended to be about 150 minutes per week.

　　Develop good habits of work and rest. Guaranteed daily 7-mdash; 9 hours of sleep, it is recommended to sleep from 10 pm to 6 am the next day.

　　Pay attention to controlling drinking and quitting smoking, and keep a good attitude. Learn to deal with things positively and peacefully in life, and don’t be overly anxious about everything.

　　Regular physical examination, arrange targeted cancer screening every year to achieve early detection and early treatment. (Source: Popular Science China)

Chilam’s self-mockery is more difficult than Wu Zhenyu’s ＂Oh Mom＂ is afraid that the other party will find Anita Yuen.

1905 movie network news May 10, byQiu LitaoDirecting,francis ng、Chilam; Julian Cheung、Charmaine Sheh、Chrissie ChauA suspense movie about criminal action starring others.The first film conference was held in Beijing.

　

At the event site, director Qiu Litao was absent from work, and the film producer Tang Wenkang appeared with starring Wu Zhenyu, Chilam and Charmaine Sheh. At the press conference, everyone spit out Tang Wenkang’s "Hong Kong Pu", and Chilam spit out, "I stood next to him, and my Mandarin has become better."

　

The director missed the opportunity to vomit. Wu Zhenyu lamented that he would play without pay

　

As the most prolific director in Hong Kong today, Qiu Litao released four works in just one year last year, and at this year’s Hong Kong International Film and Television Exhibition, at least seven works were exposed, and the film The Leaker is one of them. After finishing the post-production of The Leaker, Qiu Litao has been involved in the filming of the next work, and was absent from the press conference that day for some reason.

　

At the scene, everyone took advantage of the director’s absence, and the director Tucao was "obsessive-compulsive", especially for time.

　

Chilam said that Qiu Dao is a workaholic. Tang Wenkang, a producer on the side, even broke the news. What the director said most on the set was, "What are you waiting for? Why don’t you shoot? "

　

"Goddess" Charmaine Sheh also praised the director’s "quickness and accuracy", saying, "The director works very fast every time and the boot time is also very punctual."

　

It can be seen that the director’s high yield every year is not just as simple as "opening".

　

When talking about the director, Wu Zhenyu changed the style of "Wu was three years old" in the past, feeling that if the director asked him to make a film, even if he didn’t get paid, he would rush to play. "Because when I made a movie for the first time, Qiu Dao took the camera and took pictures for him."

　

"Wu San-year-old" believes that the male god is not as good as Chilam’s fear of the other wife’s lion roar

　

In the movie, Charmaine Sheh plays a reporter and experiences a role that is opposite to his own.

　

At the scene, the organizer turned three actors into media reporters and set the cover title of gossip magazine for themselves. This link makes Wu Zhenyu incarnate as "Wu San-year-old" and all kinds of spoof gossip. Even more, Tucao Chilam didn’t buy the title of "Chilam Charmaine Sheh Re-cooperation Classic Return". "No one will buy this title tomorrow."

　

In the final reaction test, Wu Zhenyu thought he was a male god, but he was overshadowed as soon as he met Chilam.

　

In this test, Chilam tactfully responded that he was more difficult to get along with than Wu Zhenyu, and silently said that he was "afraid of being beaten". Of course, I immediately explained, "I’m a Virgo, and I’m actually very hairy."

　

However, this is Wu Zhenyu’s absence. "When Chilam can’t hold himself, he will call his wife (Anita Yuen). I am afraid that his wife’s lion will roar."

　

It is reported that the film "Leaker" will meet the audience during the year and be ready to be released at any time.

Basic Biology of Macrophages： From Origin to Function

Written by: immune meow with picky eaters

Source: gossip Immunology

● 　　 　● 　 　　●
　
Macrophages (English name: Macrophages, abbreviated M) are immune cells widely distributed in blood and tissues of the whole body.Macrophages can devour and kill intracellular parasites, bacteria, tumor cells, as well as self-aging and abnormal cells, and play an important role in immune defense, immune homeostasis and immune monitoring.Macrophages are a kind of phagocytes and belong to monocyte system.
　
Macrophages have been a hot research object for a long time because of their diversity and heterogeneity in tissue distribution.
　

one

The origin of macrophages
　

The evolution of species diversity and struggle for existence have produced a complex host defense system, which relies on natural immunity, first single-celled eukaryotes, and then adaptive immunity in tissues and developing eukaryotes. Natural immunity was first expounded at the end of 19th century, and Elie Metchnikoff introduced the word "macrophage", which means "macro = big and phage = eater”。 Monocytes/macrophages are a small group of white blood cells determined by their location, phenotype, morphology and gene expression profile.

Monocytes account for 4-10% of nucleated cells in normal peripheral blood. In blood, the half-life of monocytes is less than 20 hours. For many years, it has been assumed that macrophages are completely differentiated from circulating monocytes, but the recent morphological and functional differences between these cells refute this hypothesis.

Recent research evidence shows that macrophages in most adult tissues are sown before birth, and during embryonic development, they are transferred from.yolk sacIt has the ability of self-renewal and is maintained independently of monocytes. In addition,Each organ has its own unique combination of embryos and adult macrophages..

Embryonic macrophages participate in tissue reconstruction, while adult macrophages mainly assist host defense. In addition to these differences, we also observed that embryonic macrophages and adult macrophages coexist in many different organs.

2

Tissue distribution of different macrophages　 　

According to their anatomical location and functional phenotype, macrophages can be divided intoMicroglial cell、osteoclast、pm, spleen tissue cells and interstitial connective tissue, liver interstitial connective tissue and kupffer cells.

There are also different types of macrophages in the intestine, which have different phenotypes and functions, but work together to maintain tolerance to normal intestinal flora and oral antigens.

There are also different numbers of macrophages in the secondary lymphoid organs, including macrophages in the marginal area of spleen, which inhibit the natural immunity and adaptive immunity to apoptotic cells, and sinus macrophages under the capsule of lymph nodes, which remove the virus in lymph and start the antiviral immune response.

differentMacrophages exist in immune immune immune sites., such as the brain, eyes and testicles, these parts are inTissue remodelinganddynamic balancePlay a central role. These tissue-specific macrophages devour dead cells, debris, foreign antigens and materials, organize the inflammatory process, and recruit more macrophages as needed.

three

Plasticity and polarization
　

Macrophages are remarkable plastic cells, which can be obtained fromConversion from one phenotype to another.. Macrophage polarization is a process. Macrophages show specific phenotypes and make functional responses to microenvironment stimuli and signals encountered in each specific tissue.

Local cytokine environment can localize macrophage polarization. The two subsets of macrophages with different functions include classic activated or inflammatory (M1) and alternately activated or anti-inflammatory (M2) macrophages. This phenomenon of these two different M1/M2 phenotypes is called.Macrophage polarization.

M1 macrophageIt is usually induced by the recognition of Th1 cytokines (such as IFN-γ and T NF-α) or bacterial lipopolysaccharide (LPS). These macrophages produce and secrete high levels of proinflammatory cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-12, IL-23 and COX-2, while the level of IL-10 is low.

Functionally, M1 macrophages participate in the elimination of pathogens during infection by activating nicotinamide adenine phosphodinucleotide (NADPH) oxidase system and then producing reactive oxygen species (ROS). Therefore, M1 macrophages have strong anti-microbial and anti-tumor activities, mediating tissue damage caused by reactive oxygen species, damaging tissue regeneration and wound healing. In order to prevent this kind of tissue damage, the anti-inflammatory effect of M2 macrophages inhibits the chronic inflammatory reaction by regulating the mechanism.

M2 macrophageSTAT6 is activated by IL-4 receptor α(IL-4Rα) and polarized by Th2 cytokines IL-4 and IL-13, which has anti-inflammatory effect. Besides IL-4 and IL-13, cytokines such as IL-10 can also regulate M2 polarization by activating STAT 3 through IL-10 receptor (IL-10 R).

IL-33It is a cytokine related to Th2 in IL-1 family and can induce M2 polarization. It is characterized by up-regulating arginase-1(arg-1), CCL 17 and CCL 24, thus mediating pulmonary eosinophilia and airway inflammation.

IL-21It is another Th2-related cytokine that drives M2 polarization. M2 macrophages have the characteristics of anti-inflammatory cytokines, which are characterized by low production of IL-12 and high production of IL-10 and TGF-β.

Functionally, M2 macrophages have strong phagocytosis, which can remove debris and apoptotic cells, promote tissue repair and wound healing, and promote angiogenesis and fibrosis. Therefore, generally speaking, M2 cells participate in Th2 response and parasite clearance, inhibit inflammation, promote tissue remodeling, angiogenesis, immune regulation, tumor formation and progress.

However, the M1/M2 phenotype does not reflect different phenotypic subsets of macrophages. According to the activation stimulus received, M2 macrophages can be further divided into four types.M2A, M2B, M2C and M2DDifferent subgroups of the composition.

M2aMacrophage subsets can be induced by IL-4 and IL-13, producing high levels of CD206, bait receptor IL-1 receptor II(IL-RII) and IL-1 receptor antagonist (IL-1RA).

Immune complex (ICs) and Toll-like receptor (TLR) agonists or IL-1 receptor ligands can induce M2b subgroup.M2bMacrophages simultaneously produce anti-inflammatory and pro-inflammatory cytokines IL-10, IL-1β, IL-6 and α-α.

M2cCells were induced by glucocorticoid and IL-10, and showed strong anti-inflammatory effect on apoptotic cells by releasing a large amount of IL-10 and transforming growth factor-β.

Finally, TLR agonist induced the fourth M2 macrophage through adenosine receptor agonist.M2d.

The activated receptor of adenosine then inhibits the production of pro-inflammatory cytokines, induces anti-inflammatory secretion of cytokines (high IL-10, low IL-12) and vascular endothelial growth factor (VEG F), thus providing a drug withTumor associated macrophages (TAMS)The angiogenic characteristics of the characteristic. M2 macrophages exposed to M1 signal, or conversely, induced differentiated macrophages to "repolarize" or "reprogram" is another evidence that they have high functional plasticity and can potentially pursue therapeutic goals.

four

hugeMigration of phagocytes

Monocytes and macrophages migrate to the site of inflammation or injury to eliminate the initial inflammatory signal and ultimately promote wound healing and tissue repair.

This process is mainly initiated by pathogen-related molecular patterns (PAMPs) (released from invasive pathogens) and damage-related molecular patterns (DAMPs) (released from damaged or dead cells to cope with infection and injury).

In addition, antigen can activate memory T cells in tissues through secretion.manyInflammatory cytokines and chemokines are used to trigger the recruitment of macrophages. Chemokines directly participate in the migration and activation of monocytes through endothelium, and monocyte chemoattractant protein -1 (MCP-1) is a monocyte chemotactic factor, which participates in the occurrence of inflammation and induces monocyte chemotaxis and migration by interacting with CC chemotactic factor 2(CCR2) on monocytes. MCP-1 is mainly secreted by activated fibroblasts, endothelial cells, vascular smooth muscle cells (VSMC), monocytes and T cells. MCP-1, together with IL-8 or CXC ligand -8(CXCL-8), can trigger the firm adhesion of monocytes to vascular endothelial cells under blood flow conditions. Monocyte adhesion and migration across endothelium through activated venule wall is a basic immune response, which depends on the expression of adhesion molecules of chemical mediators on the surface of vein endothelium.

These adhesion molecules belong to four families:Selectin、Integrin、Immunoglobulin superfamilyandMucin-like glycoprotein.

five

Antigen presentation

Antigen presenting cells, mainly macrophages, are the outposts of the immune system that starts and regulates immune response. An important feature of macrophage biology is the capture, endocytosis and expression of self or foreign antigens, which providesThe connection between innate immunity and adaptive immunity.

Macrophages reside in surrounding organs, where they monitor surrounding tissues for invading pathogens. They alert the immune system to the presence of pathogens by engulfing them, processing their antigens and presenting peptide fragments that bind to human leukocyte antigen (HLA) molecules. After antigen treatment, macrophages migrate to T cells and stimulate them. Activated macrophages express high levels of costimulatory molecules and antigen presenting molecules on their surfaces, such as CD 80, CD 86 and MHCⅠ ⅰ and ⅱ molecules. Mixed Leukocyte/Lymphocyte Reaction (MLR) is used as a basic test for determining the function of macrophages, because it measures the proliferation ability of macrophages to allogeneic T cell populations.

six

Production of cytokine and chemokines

Interleukin is a kind of cytokine, which is involved in inducing adhesion molecules, matrix metalloproteinases (MMP), angiogenic factors and signal pathways, such as nuclear factor kappa B(NF-kB) and signal transduction and transcription activator (STAS) involved in tumor invasion and angiogenesis.

Activation of M1 macrophages can induce proinflammatory cytokines., including TNF-α, IL-1α, IL-1β, IL-6, IL-12, IL-18 and IL-23; Produce nitric oxide (NO), reactive oxygen species (ROS) and RNS；; Antigen presentation; Expression of CC chemokine receptors CCR1 and CCR5; Promoting T-helper type 1 (Th1) and Th17 responses provides an effective mechanism for killing.

Obviously, M1 and M2 macrophages have different chemokine profiles, while M1 macrophages expressing Th1 cell chemokines, such as CXCL9 and CXCL10.

M2 macrophages express chemokines.CCL17, CCL18, CCL22 and CCL 24. M1 macrophages express inflammatory cytokines TNF-α, IL-1β and IL-6, and together with costimulatory molecules CD 40, CD 80 and CD 86, they up-regulate MHCⅡ class II molecules to promote cytotoxic adaptive immunity.

M1 macrophages express Th1- and Th17- polarized cytokines IL-12, IL-23, IL-27 and Th1- aggregation chemokines CXCL 9, CXCL 10 and CXCL 11. On the contrary, M2 macrophages support the resolution of inflammation by transferring gene expression to anti-inflammatory molecules such as IL-10, TGF-β, IL-1R1Ⅱ and IL-1Ra. M2 macrophages also express a large number of endogenous receptors, including scavenger receptor CD 163, stabilizer -1 and type C lectin receptor CD 206, CD 301, Dectin-1 and CD 209. In addition, M2 macrophages recruit Th2, regulatory T cells (Tregs), eosinophils and basophils by secreting chemokines such as CCL 17, CCL 18, CCL 22 and CCL 24..

seven

Macrophage apoptosis

Apoptosis is a normal, physiological and necessary process of cell selection and survival, eliminating and removing unnecessary cells, such as aging, damaged, genetic mutation and virus-infected cells; In fact, anti-apoptosis can promote malignant transformation of normal cells.

At present, it is known that macrophage apoptosis is related to various stages of the disease related to the decline of pathogen activity, which can be regarded as a natural immune defense mechanism and strategy for the host to limit infection against intracellular pathogens.

On the contrary, many cellsPathogens have the ability to kill infected cells., destroy the host pathway, inhibit cell apoptosis, leading to necrosis. This strategy can makePathogens escape the host’s immunity and infect other nearby or distant cells.. These apoptotic infected cells also provide a link between innate immunity and acquired immunity. When professional APCs absorb apoptotic vesicles, this connection begins when bacterial products and pathogenic antigens enhance T cell activation. Similarly,Pathogens inhibit apoptosis and promote necrosis.It also impairs the presentation of bacterial antigens, which may be the mechanism of immune escape.

In atherosclerosis, macrophages die by reducing the number of cells in the lesion, which is beneficial to reduce the lesion area. In the progress of atherosclerosis and other diseases, the phagocytosis of M2 macrophages solves the problem of apoptosis and its adverse effects. This unique functional feature of M2 macrophage is caused byHigh level of scavenger receptorExpress support.

Macrophages phagocytize debris, injured cells, dead cells and apoptotic cells, and inhibit macrophages from producing pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin -1β, interleukin -6 and interleukin -8. The mechanism involves autocrine or paracrine of transforming growth factor -β(TGF-β), thus inhibiting further recruitment of monocytes and macrophages.

In addition, the phagocytosis of apoptotic cells inhibits the production of pro-inflammatory IL-12, IL-23 and IL-27 and stimulates the production of anti-inflammatory IL-10.

By limiting the phagocytosis of local inflammation, it can also protect tissues from harmful pro-inflammatory reactions, death, injury and the immunogenic content of dead cells, and throughNecrosis after apoptosis to protect the growth of lesions.

In the late stage of atherosclerosis, the phagocytic function of apoptotic cells is seriously damaged, which leads to the aggregation of macrophages and vascular smooth muscle cells, which eventually blocks the decomposition of inflammation and promotes local necrosis, inflammatory state and plaque instability.

Understanding the exact mechanism of pathogen inhibiting apoptosis can avoid natural immunity and adaptive immunity, which provides a new strategy for optimizing treatment. The idea of manipulating the host or bacterial pathway to induce more cell apoptosis, "apoptosis-promoting therapy", may help to produce a more effective immune response.

eight

Macrophage metabolism

Recent evidence shows that metabolism plays an important role in the formation of macrophages and the obvious polarization phenotype. Under normal, physiological and pathological conditions, macrophages face an oxygen gradient.Macrophages adapt to hypoxia by shifting their metabolic pathways to glycolysis.. In addition, the activation of hypoxia-inducible factors (HIF)-1 and -2 caused profound functional changes, including the expression of chemokines and chemokine receptors, such as CXC chemokine 4(CXCR 4), CXCL 12, angiogenesis factor and vascular endothelial growth factor (VEGF)(Biswas and Mantovani, 2012; Orihuela et al., 2016). Therefore, macrophages help to coordinate the response of tissues to oxygen gradient and hypoxia conditions.

Macrophages M1 and M2 can obviously regulate the metabolism of glucose, amino acids, iron and folic acid.After macrophage activation, its metabolic pathway changes from oxidation to glycolysis.solve. Under the action of M1 stimuli (such as LPS, Th1 cytokines and IL-12), they showed a metabolic transformation to anaerobic glycolytic pathway, while M2 stimuli (such as IL-4 and IL-13) had little effect. Macrophages activated by IFN-γ and L-PS are often associated with acute infection, so it is necessary to trigger strong antimicrobial activity quickly in hypoxic microenvironment. In this case, the anaerobic process such as glycolysis is the best way when energy is needed. Interferon-γ and lipopolysaccharide strongly induce glucose uptake and inhibit fatty acid uptake and oxidation. Therefore, glycolysis metabolism is enhanced and mitochondrial activity is decreased.

On the contrary,M2 macrophage functions, such as wound healing and tissue repair, need continuous energy supply.. This requirement is made byGlucose oxidative metabolism and fatty acid oxidationProvided, andFatty acid oxidation is the most important metabolic pathway of M2 macrophages.. M2 macrophage has the characteristics of high mitochondrial activity and oxidative phosphorylation. They show enhanced respiratory activity based on fatty acid β oxidation. Both metabolic pathways are up-regulated in the process of macrophage activation, but glycolysis is the main metabolic pathway, which can produce DNA and cell membrane synthesis substrates and promote the growth and differentiation of monocytes. It is another possibility of glycolytic metastasis of M1 macrophages to produce rapid and optimal response at the infected site.

In addition, the accumulation of citric acid in M1 macrophages is essential for the production of pro-inflammatory mediators NO, ROS, RNS and prostaglandin. Another important aspect is the metabolism of amino acids closely related to the functional phenotype of macrophages. M1 macrophages are characterized by the expression of inducible nitric oxide synthase (iNOS).The production of NO is an important anti-microbial effect. M1 macrophages are active, while M2 macrophages do not produce NO.. On the contrary, they express high levels of Arg-1 and play a role in catalyzing the production of polyamines, which are necessary for collagen synthesis, cell proliferation, fibrosis and other tissue remodeling functions. Interestingly, the production of polyamines is reported to be the driving factor of M2 polarization.

In addition, there are significant differences in iron metabolism between M1 and M2 macrophages. Although M1 macrophages express a large number of iron storage proteins, such as ferritin, the content of iron porphyrin they express is low, and ferritin is the export of iron. Compared with M1 type macrophages, M2 type macrophages have lower ferritin content, but higher ferritin content. This different iron metabolism may be related to its function. Because iron is necessary to support the growth of bacteria, the retention of iron in M1 macrophages is a kind of bacteriostasis and supports the host’s protection against infection. On the contrary, the iron released by M2 macrophages is beneficial to tissue repair, but it can cause tumor growth and metastasis.

Metabolic adaptation is an important aspect of macrophage polarization and its functional activities.

nine

MicroRNA involved in macrophage polarization

MicroRNA plays an important role in many aspects of macrophage biology, thus affecting many biological and pathological conditions, such as monocyte differentiation and development, macrophage polarization, infection, atherosclerosis, tumor growth, inflammatory activation, cholesterol homeostasis, cell survival and proliferation, and phagocytosis.

MiRNA-24, miRNA-30b, miRNA-142-3p and miRNA-199a-5p can inhibit the differentiation of monocytes into macrophages.

M1 macrophage polarizationMiRNA-125, miRNA-146, miRNA-155, miRNA-7a/f and miRNA-378 are needed, andM2 polarizationThen miRNA-let-7c/e, miRNA-9, miRNA-21, miRNA-146, miRNA-147, miRNA-187 and miRNA-223 are needed.

In addition, miRNA-342-5p promotes NO synthesis, and IL-6 provides pro-inflammatory signals for macrophages. Although miR-21 has been proved to have both pro-inflammatory and anti-inflammatory effects, its anti-inflammatory effect is more prominent. MiR-155 and miR-142-3p inhibited the proliferation of macrophages compared with let-7a. MiR-155 can promote and prevent apoptosis at the same time, while miR-21 and let-7e negatively regulate the apoptosis of macrophages.

Main references

Abbas Shapouri Moghaddam，doi:10.1002/jcp.26429，2018

Thomas A. Wynn，Nature，doi:10.1038/nature12034，2013

Nicole J. Horwood，Clinic Rev Allerg Immunol，doi:10.1007/s12016-015-8519-2

Baojun Automobile responded to the rumor of ＂brake failure＂： it was actually a software BUG that led to the degradation of brake power.

Recently, Baojun Automobile made a public response to the rumor on the Internet that Baojun Yue also had "brake failure" on the official Weibo. Baojun Automobile made it clear that the so-called "brake failure" is not accurate. In fact, some vehicles have software bugs, which leads to the degradation of the brake assist system. For this part of the affected vehicles, there will be an indicator light to remind them when starting, and they will automatically enter the speed limit protection state to ensure driving safety.

Baojun Automobile stressed in the statement that after receiving feedback from relevant users, the company quickly took action and solved the problems involving vehicles, and asked users to use them with confidence. Baojun Automobile also pointed out that some media used inaccurate descriptions such as "brake failure" without fully understanding the facts, and there were inaccurate information.

Baojun Automobile said that the company will sincerely and properly cooperate with the owner to handle the follow-up matters to ensure that the rights and interests of users are properly protected. The handling of this incident also reflects Baojun Automobile’s attention and commitment to product quality and user safety.

Stealing trade secrets, a Chinese businessman who lost 700 billion yuan to China, was released from prison yesterday.

Every edited Wang Jiaqi　　　　

At the regular press conference of the Ministry of Foreign Affairs yesterday (July 4th), a name that had disappeared for eight years was suddenly mentioned again — — Hu Shitai, an Australian Chinese businessman.

On March 29, 2010, the Shanghai No.1 Intermediate People’s Court ruled in the first instance that the defendant Hu Shitai was sentenced to 10 years’ imprisonment, confiscated property and fined RMB 1 million for the crimes of accepting bribes and infringing commercial secrets by non-state staff.

On May 17, 2010, the Shanghai Higher People’s Court issued a public verdict in the second instance, rejecting the defendant’s appeal and upholding the judgment of the first instance.

Lu Kang, a spokesperson for the Ministry of Foreign Affairs, said: Hu Shitai abided by the prison rules and discipline and obeyed management education during his prison term. China judicial authorities ruled that his sentence was reduced according to law. Hu Shitai was released from prison on July 4.

▲ Hu Shitai (data map, source: Oriental IC)

At that time, the "Hu Shitai case" shocked the whole world and shook the entire steel and mineral industry. In the first decade of the 21st century, Hu Shitai was well known in China’s steel industry. How powerful was his "energy"? Look at a set of data:

Since 2003, China steel enterprises have spent more than 700 billion yuan just because of the rising iron ore price in the past six years, which is equivalent to more than twice the total profits of China steel enterprises in the same period. Even in 2008, when the financial crisis broke out, China once again accepted that the price of fine ore rose by 79.88% and lump ore rose by 96.5%, which was the highest increase in history.

Behind this, of course, there is a problem of global iron ore pricing mechanism; But in this mechanism, Hu Shitai "contributed".

To review the Hu Shitai case, we have to start with the global iron ore pricing mechanism.

Before 1950, the global iron ore trading mode was mainly spot trading; In the 1960s, Japan became the main buyer of iron ore in Australia, and the two sides started to sign short-term contracts, which gradually developed into long-term contracts in the late 1960s, and the quantity and price of iron ore were locked for 10 to 20 years.

In 1980, the annual long-term negotiated price mechanism of iron ore began to take shape. Every year, the global major mines (iron ore supply side representatives) and major steel mills (demand side representatives) negotiate to determine the annual iron ore supply price. This process is also called "iron ore negotiation". The fixed price is the industry index, which is widely referenced and adopted in other trade negotiations.

However, it was not until 2003 that China joined the "iron ore negotiations". At that time, China was already the largest producer and consumer of steel. However, from 2003 to 2009, China was almost defeated in the annual price game. As the largest iron ore buyer in the world, it had no pricing power.

Who were the buyers and sellers at that time?

Seller:

BHP Billiton (BHP Billiton)

BHP Billiton was formed in 2001 by the merger of two giant mining companies-BHP and British Billiton Company, which was then the largest mining company in the world.

Companhia Vale Do Rio Doce

At that time, the world’s largest iron ore producer and exporter was also the largest mining company in the American continent.

Rio Tinto mining company (Rio Tinto)

It was founded in Spain in 1873. In 1954, the company sold most of its Spanish business. From 1962 to 1997, the company merged several influential mining companies in the world, and in 2000, it successfully acquired the Australian Northern Mining Company, becoming a global leader in the exploration, mining and processing of mineral resources.

Buyer:

China Iron and Steel Industry Association.

Domestic steel enterprises.

What role did Hu Shitai play in the negotiation?

Hu Shitai was born in 1963, originally from Tianjin, China. He graduated from Peking University and went to Australia to study. After graduation, he went to work in Hammersley Iron Mine, Australia’s second largest iron ore producer. After Rio Tinto acquired Hammersley Iron Mine, Hu Shitai became an employee of Rio Tinto. Joined Australian citizenship in 1997,

Hu Shitai has worked in Rio Tinto for quite a long time and is familiar with major domestic steel mills and ore traders. When the case was investigated, Hu Shitai was the chief representative of Rio Tinto, an Australian iron ore enterprise, and the general manager of Rio Tinto’s Hammersley iron ore business in China. At that time, he was a member of Rio Tinto’s "iron ore negotiations".

▲ August 5, 2010, Shanghai, Rio Tinto China Office (Source: Oriental IC)

It is this one-sided negotiation pricing mechanism that makes Hu Shitai see "business opportunities".

The case broke out in 2009.

On July 5, 2009, four employees of Rio Tinto Shanghai Company were detained. Among the four people detained, Hu Shitai was included. At the same time, the public security department also took away his computer.

Subsequently, Xinhua News Agency reported that Hu Shitai and other four people were detained because they used improper means to win over the insiders of China iron and steel production units during the iron ore import and export negotiations between China and foreign countries since 2009, and used this to spy on and steal China’s state secrets.

At that time, an insider revealed to national business daily (micro-signal: nbdnews) that the computer of Rio Tinto’s Shanghai office taken away by the relevant departments contained dozens of steel enterprises with long-term contracts with Rio Tinto. These data relate to the detailed procurement plan, raw material inventory, production arrangement and other data of the enterprise, and even the monthly steel output and sales of some large steel enterprises are very clear.

"(Rio Tinto) knows the situation of steel mills in China like the back of his hand," said the insider. "Mines even know their companies better than the bosses of some enterprises." Some people who have close contacts with the mine also said.

At that time, a relevant person of a steel enterprise said, "In our company, there are no more than 10 people who can know the details of raw material inventory, production arrangement and sales." Mines can master these enterprise secrets, and may have already bought off the specific production and operation personnel of related enterprises.

Many people in iron and steel enterprises said that Hu Shitai was "very happy" in China’s iron and steel industry, and he had a good personal relationship with many heavyweights in the steel industry, including Tan Yixin, then assistant general manager of Shougang International and general manager of mining import and export company. A few days before Hu Shitai was detained, Tan Yixin was also formally arrested by the procuratorate for allegedly providing commercial secrets to Hu Shitai and others and bribing state employees.

Having monopolized the global mineral resources, and now knowing the situation of China iron and steel enterprises clearly, how can China enterprises succeed at the negotiating table?

Let’s talk about Hu Shitai’s bribery crime.

The court found through trial that from 2003 to 2009, Hu Shitai and Chinese employees Wang Yong, Ge Minqiang and Liu Caikui took advantage of their positions to solicit or accept money for many times in iron ore trade with China to seek benefits for others.

Among them, Hu Shitai received RMB 6.46 million, Wang Yong received RMB 75.14 million, Ge Minqiang received RMB 6.94 million and Liu Caikui received RMB 3.78 million.

There are 20 domestic steel enterprises that pay bribes to them. There are many ways for Hu Shitai to accept bribes and make profits for others. Here is an example:

After Guofeng Iron and Steel signed a long-term contract with Rio Tinto with an annual capacity of 1 million tons for five years, Hu Shitai asked the company for the calculation standard of the benefit fee, which was 30% of the profit of a ship. In order to become a long-term cooperative company with more favorable goods, Guofeng Iron and Steel Co., Ltd. was turned around by many people and companies, and nearly $800,000 in benefits was paid to Hu Shitai.

Liu Caikui, one of Hu Shitai’s four people, mostly accepts bribes from enterprises without iron ore import qualifications. They must rely on the names of some steel companies that have entered the long association sequence to purchase iron ore from Rio Tinto. It is natural for the relevant enterprises to pay Liu a certain fee after getting the ore.

In order to get the iron ore contract, he paid bribes to Hu Shitai and others, reflecting the passive situation of China steel enterprises at that time:

Around 2004, the long-term price of iron ore was much lower than the spot price, and the highest price difference exceeded 100 US dollars/ton. Iron and steel enterprises and traders who are qualified to import iron ore and hold long-term orders resell iron ore to the spot market, which is even more profitable than doing the main business of steel.

Before the financial crisis in 2008, Rio Tinto rarely directly signed long-term agreements with traders and small steel enterprises. With the advent of the financial crisis, when the long-term cooperative price was higher than the spot price, large steel enterprises in China and other long-term cooperative customers defaulted in a large area. In order to obtain the maximum benefit, Rio Tinto began to contact with small and medium-sized steel enterprises in iron ore negotiations, and as long as it reached a certain amount, it could make some discounts (sell the ore) to small and medium-sized steel enterprises. As a breakthrough of "iron ore negotiation".

▲ Image source: Photo Network

From being detained on July 5, 2009 to serving his sentence on July 4, 2018, nine years later, Hu Shitai walked out of the cage. He may find that the iron ore market has changed. And the change happened from the time he was sentenced.

In 2010, China rejected the annual benchmark prices agreed by the three major mines, and the annual negotiations of the Iron Ore Association broke down, and the pricing model linked to the index was adopted. Spot iron ore is priced on the basis of index. The purpose of this pricing method is to reflect the spot market situation and the relationship between supply and demand.

At that time, another giant BHP Billiton also said that nearly half of the company’s customers had begun to adopt a pricing system linked to the spot market. This shows that the old mechanism for setting the annual price of iron ore is losing its meaning.

With the development of spot market and the rise of index pricing, iron ore derivatives trading came into being. In 2009, Singapore Stock Exchange launched the world’s first iron ore swap contract. In the domestic market, Dashang launched an iron ore futures contract in 2013, which was denominated in RMB and delivered in kind.

Every time Xiaobian (micro-signal: nbdnews) noticed that although the iron ore negotiation is controlled by people no longer exists, the international crude oil price has risen sharply this year, and the pricing power of bulk commodities is still in the hands of international energy giants and financial predators. How to reverse this situation? How to safeguard the core interests of enterprises in China?

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