Since the beginning of this year, innovative pharmaceutical companies have gone out to sea again. Pharmaceutical companies such as Yaoming Bio, Maiwei Bio and Anrui Bio have announced that they have reached overseas authorized transactions. The insiders believe that intensive overseas authorized transactions fully prove that the R&D strength of innovative pharmaceutical enterprises in China has been recognized by international pharmaceutical companies. The ecological pattern of domestic biomedical industry is being reshaped, and the mode of cooperation with foreign pharmaceutical companies will be more diversified in the future. With the adjustment of industry structure, it is expected that 2024 will be a year in which transactions and mergers and acquisitions among pharmaceutical enterprises will become more frequent.

　　R&D strength continues to increase.

　　With the rapid development of the industry, the research and development strength of biomedical enterprises in China has been continuously enhanced. According to incomplete statistics, there were at least 120 overseas authorized transactions of innovative drugs in China from 2021 to 2023, with a total transaction amount of nearly $85 billion. In 2024, innovative drugs went out to sea to speed up. As of January 14th, domestic enterprises have completed more than 10 foreign authorization transactions, including many transactions exceeding 1 billion US dollars.

　　Genxi Bio has announced that AstraZeneca has completed the acquisition of the company. After the merger, Genxi Bio became a wholly-owned subsidiary of AstraZeneca. AstraZeneca previously said that the acquisition of Genxi Bio will further consolidate AstraZeneca’s strength in the field of cell therapy.

　　Since the beginning of this year, several products of Anrui Bio have obtained overseas authorization, including an exclusive option and a global license agreement with AstraZeneca, and the development and commercialization of a new allosteric inhibitor targeting the mutation of epidermal growth factor receptor (EGFR)L858R as a potential new treatment for advanced EGFR mutation non-small cell lung cancer (NSCLC). With the transfer agreement with Avenzo Therapeutics,Inc.(Avenzo) of the United States, Avenzo will gain the global (except Greater China) development and commercialization rights of a cyclin-dependent kinase 2(CDK2) selective inhibitor ARTS-021 independently developed by Anrui Bio, and another pre-clinical project will be submitted to IND (new drug clinical trial) in early 2025.

　　Ding Qiang, co-founder and CEO of Anrui Bio, said that through cooperation, the company can obtain significant economic benefits and accelerate the development and listing of innovative drugs.

　　Chen Kan, a partner of Qiming Venture Capital, said that the cooperation between Anrui Bio and foreign pharmaceutical companies all involved small-molecule drugs, which on the one hand proved Anrui Bio’s research and development strength, and on the other hand reflected that small-molecule drugs could also be "put out to sea".

　　In addition to well-known biotech listed companies, there have been an increase in overseas authorized transactions of small biotech companies such as Yilian Bio, Anrui Bio and Bowang Pharmaceutical, as well as traditional pharmaceutical companies such as Hengrui Pharma and Haosen Pharmaceutical.

　　In Chen Kan’s view, China pharmaceutical companies and overseas pharmaceutical companies have reached a heavy cooperation, reflecting the recognition of domestic new drugs by international pharmaceutical companies. At the same time, domestic pharmaceutical companies can get cash support. In the process of cooperation with large international pharmaceutical companies, including joint promotion of clinical trials, China Biotechnology Company can also learn a lot of experience.

　　Share risks and obtain resources.

　　Ding Qiang said that cooperation with overseas pharmaceutical companies should be based on comprehensive consideration of the company’s strategic objectives, research and development capabilities and market demand. The cooperation between the company’s two pipelines and AstraZeneca and Avenzo Therapeutics is based on comprehensive considerations. Drug R&D costs a lot and risks are high. Cooperation with large pharmaceutical companies can share risks to a certain extent, especially in clinical trials and marketing stages. In addition, cooperation with overseas pharmaceutical companies can obtain many resources, including funds and market channels, which is very important for accelerating product development and commercialization. Of course, cooperation needs to consider whether the goals of both parties are the same, whether they can support their long-term development strategy, and how to protect their intellectual property rights and avoid the loss of core technologies.

　　Sinopharm plays an important role in two overseas authorized projects reached by Anrui Bio. It is reported that Sinopharm is an innovative company focusing on helping domestic biomedical enterprises to authorize projects overseas. Ding Qiang introduced that Sinopharm provided the whole process service for the company, from the preparation and modification of materials, strategic analysis and optimization, to assisting Anrui to connect and communicate with potential partners, and to negotiate and negotiate relevant terms, which greatly helped the company to reach overseas authorization.

　　For pharmaceutical companies planning to "go out to sea", Jung Lee, senior vice president of business development of Sinogold Pharmaceuticals, suggested that China Biotechnology Company must ensure that the product lines are differentiated and meet the unfinished medical needs. In addition, setting up branches overseas can better understand the current biotechnology trends and cutting-edge scientific progress.

　　Ding Qiang said that enterprises planning to go to sea need to have the world’s leading scientific research strength and unique product innovation. At the same time, it is necessary to deeply understand the situation of potential partners, especially the pipeline layout and the overall strategy of the enterprise. Multinational pharmaceutical companies have their own strategic direction and different layouts in different fields of disease treatment. A deep understanding of the business scope, market strategy and corporate culture of their partners can help the two sides establish closer and more efficient cooperative relations. In the cooperation agreement, many terms and details need special attention, including key factors such as intellectual property ownership, economic sharing, milestone payment, etc. It is necessary to make legal risk assessment and compliance preparation in advance to ensure that the cooperation activities meet the requirements of local laws and regulations.

　　Watch the three subdivided tracks

　　Looking forward to 2024, Chen Kan judged that the number of pharmaceutical companies "going out to sea" in China will remain high. From the past transactions, the clinical data of pharmaceutical companies in China have gained more and more global recognition. Overall, we are optimistic about the three sub-segments of tumor, metabolism and autoimmune.

　　Chen Kan believes that it is necessary for most new drug R&D companies to "go out to sea", especially to develop some small varieties of new drugs that are less suitable for people. Drug pricing in overseas markets is relatively high, and pharmaceutical companies "going out to sea" can expand the market and improve the input-output ratio. The domestic pharmaceutical industry will improve in 2024.

　　From the perspective of cooperation modes, Chen Kan said that there are more and more cooperation modes for domestic and foreign pharmaceutical companies, including obtaining down payment through overseas authorization, acquisition and joint development. Jung Lee believes that more and more innovative drugs from China will go global, and there will be more transactions between China biotechnology companies and multinational pharmaceutical companies than before.

　　Great Wall Securities believes that the "going out to sea" mode of Chinese pharmaceutical enterprises is mainly based on overseas authorization. From January 1 to February 4, 2024, the amount of overseas authorized transactions in China reached 9.146 billion US dollars. In 2024, China’s pharmaceutical "going out to sea" is expected to explode.

　　Chinese pays attention to traditional etiquette, and the Prime Minister is no exception. On February 13th and 25th of the twelfth lunar month, Li Keqiang walked into Pudong Village, a Dong stockade deep in the mountains of Liping County, and brought a rich "New Year Gift Package" to the villagers.

　　1. Send special products out of your own pocket

　　What’s in the "spree"? First of all, of course, those local specialties that the Prime Minister personally selected and bought out of his own pocket. On the morning of 13th, when Li Keqiang inspected the supply of Spring Festival market in Liping market, Guizhou, he also prepared a "gift package" for visiting poor households in mountainous areas in the afternoon.

　　In order to ensure that these new year’s goods really meet the needs of villagers in Dongzhai, the Prime Minister never forgets to ask every time he passes a booth: What should the local people prepare for the New Year? What sells best? Finally, under the enthusiastic "sales promotion" of the stall owners, the Prime Minister paid several times and purchased several large packages of local specialties.

　　In the afternoon, Lin Xianping, a poor villager in Pudong Village, took over from the Prime Minister in his drafty wooden building.Pickled fish, Ciba, rice wine, Dong fruit, melon seeds, fried rice and other local specialties..

　　However, despite consulting local market vendors, the Prime Minister is still a little uneasy about his "gift package".

　　"How’s your mouth? Can these be chewed? " He asked Lin Xianping’s parents who were over seventy. After receiving a positive reply, the Prime Minister showed a satisfied smile.

　　2. Dangerous houses in villages will be rebuilt.

　　In addition to the "visible" special products of the New Year, Li Keqiang also brought some invisible "gifts" to the villagers. Next to the charcoal stove in Lin Xianping’s kitchen, the Prime Minister and the Lins sat around chatting and asked them how much land they had, whether the food was enough, how much the minimum living allowance was every month, and whether they had joined the medical insurance.

　　He also specially opened the rice jar for storing surplus grain, grabbed a handful of grain and rubbed it: "This is glutinous rice! No wonder you just said that you can only play 400 kilograms per mu of land. "

　　A village cadre next to him smiled and said: "The Prime Minister has been a branch secretary of the brigade, and he is familiar with these!"

　　Lin Xianping told the Prime Minister that he now has a minimum living allowance and joined the new rural cooperative medical system, and the harvest of farming can also guarantee food rations, but the biggest difficulty at home is that the house is too shabby and has no money to repair it.

　　"You show me!" Li Keqiang got up at once, climbed up the second floor along the shabby wooden stairs and frowned at the leaking windows and old wires.

　　"If this catches up with mountain torrents and windstorms, how can people live in a tight place? It will be even worse in case of fire! " He said, "this is a pain in our hearts!" "

　　After leaving the Lins’ wooden house, Li Keqiang told the local person in charge that Pudong Village must be included in the system arrangement of centralized contiguous poverty alleviation and development and precise poverty alleviation.

　　He said loudly to the villagers who gathered around him: "The government is determined to transform your village, and you must live in a safe and comfortable new house and live a real’ new countryside’ life!"

　　3. Drinking water is safe and secure

　　Pudong Village is a national first-class poverty-stricken village. More than 43% of the people in the village are poor, and the annual per capita net income is only 2160 yuan. Many houses are leaking everywhere.

　　"Yes, the water is still very clear." He nodded and said.

　　In last year’s "Government Work Report", Li Keqiang promised to solve the problem of drinking water safety for another 60 million rural people throughout the year. During his inspection in Pudong Village, he was particularly concerned about whether these promises were really fulfilled and whether the policies were really implemented.

　　The prime minister told the responsible person that the government promised not only to complete the task in quantity, but also to stand the test in quality. He said: "Let the people drink safe and secure drinking water, which is a hard promise of the government and must not be discounted!"

　　Also receiving the "gift package" are two village doctors in the village health center.

　　Li Keqiang has always attached importance to the irreplaceable role of village doctors. Last year, in the grass-roots investigation in Chifeng, Inner Mongolia, after discussing with the accompanying department heads, Li Keqiang decided to use all the basic public health service fees newly added by the central government in that year to subsidize village doctors.

　　During this visit, Li Keqiang asked two village doctors whether they had received the new subsidies from the state and whether the income from practicing medicine every month could guarantee their living. A village doctor replied that his income has improved, but he still needs to plant some fields when there are no patients, subsidy income.

　　After listening to this, the Prime Minister said with emotion that the government should make efforts to make you feel at ease and seek medical treatment! He revealed at the scene that the new basic public health service fees at the grassroots level this year will still be fully subsidized to village doctors.

　　"Village doctors are the’ first line of defense’ for villagers’ health. You are carrying a medicine box and wading through the mountains, reflecting the feelings of doctors to save the world." Li Keqiang said, "The government should completely eliminate your worries and let you go all out to seek medical care!"

　　5. Student loan scheme.　

　　Li Keqiang conducted a "market survey" for college students and graduates who returned home for the Spring Festival before sending out the "gift package". When sitting around the Dong Drum Tower to communicate with everyone, the Prime Minister directly asked: "What is your biggest difficulty? Speak out boldly! "

　　A girl said that she was admitted to a university in Shanghai and applied for a student loan. However, after being admitted to a graduate school in Guizhou University, she found that the student loan could not be transferred across provinces, so she had to find a way to repay the loan while attending graduate school.

　　"She hasn’t got a job yet. How can she repay the loan?" Li Keqiang turned to ask the person in charge of the relevant departments of his peers, "This issue is not a trivial matter, but a big one involving educational equity and coordinated regional development. We encourage college students to go home and go back to the west after graduation, but objectively, the income in the west is indeed lower than that in the east, and the pressure on these graduates to repay loans will be even greater. "

　　He promised at the scene that the State Council would study and formulate new policies for this purpose. The college students who received the "gift package" immediately clapped their hands and cheered.

　　6. Villagers return gifts to the Prime Minister

　　In addition to bringing these generous "New Year’s Gift Packages" to the villagers, Li Keqiang also received gifts from the villagers.

　　After learning that her dangerous house will be rebuilt, Lin Xianping’s mother excitedly took out a pack of "Baba" made by herself, hoping to give it to the Prime Minister to express her feelings.

　　Li Keqiang quickly waved his hand: "Your family is very difficult. I can’t accept this gift!"

　　Unexpectedly, the 70-year-old man chased all the way to the small bridge at the entrance of the village, saying that he would put BaBa into the hands of the Prime Minister.

　　"All right, but there are too many bags. I can only take one." Unable to overcome the enthusiasm of the old man, Li Keqiang finally accepted a small piece of Baba. This is actually a heavy heart.

　　The Prime Minister said: "I have taken away your thoughts and will always miss you. The government will definitely complete the renovation of your dangerous houses as soon as possible, and it will also give more children in the village the opportunity to go to college and let you all live a good life! "

Yet we called and urged a thousand times before she started toward us! The second model of Xiaomi Auto, YU7 (pronounced Y-U-7), was officially announced, positioning a pure electric SUV, and it is expected to be officially launched to the market during June and July 2025.

The body size of YU7 is 4999mm long, 1996mm wide and 1600mm high, with a wheelbase of 3000 mm.. The styling design continues the SU7 style, especially the details such as the front contour, headlights and taillights, which are the "family" characteristics of Xiaomi.

According to the application information, YU7 will be adopted. The peak power of the front and rear motors is 220kW and 288kW respectively, and the top speed is as high as 253km/h with Contemporary Amperex Technology Co., Limited.

Tyre size has two options, the basic version is 245/55 R19 and then 245/50 R20, and the front rim is small and then large. Optional upgraded version of the front 245/45 R21 and rear 275/40 R21 specifications, the rim size is the same, but the front is narrow and the rear is wide, which is a typical sports orientation. The brake disc is perforated and ventilated, and the front wheel is equipped with Brembo four-piston calipers.

Combined with the official map and some information previously exposed, we can see the detailed design adjustment and partial configuration of YU7. Comprises a headlight without a lampshade design, and the upper part is changed into a hollow air inlet; Unique black layered wheel arch; Full-coverage front cover and hidden inner button door handle, etc., these details are "heart to heart" with Ferrari.

The black bump on the lower edge of the front windshield may be integrated with a wrap-around HUD. Previously, a test car was photographed with a similar configuration. There is a camera on the B-pillar, which is likely to be a smart driving sensor, or the supporting face will be unlocked.

Lei Jun said that the reason why it will not be listed until the middle of next year is because a lot of road tests are still needed. After the appearance is announced, the body camouflage can be removed, making the test more comprehensive and detailed.

During the first half of next year, it is very likely that Tesla’s new version of Huan will be officially launched, when the two cars will face direct competition. Do you think Xiaomi’s new car sales can surpass Tesla’s? How much will you start pricing this car? Leave your opinion in the comments section.

Writing is the foundation of civilization and an important symbol of human civilization. Chinese characters are the most important carrier to record and inherit Chinese culture, and they are the cultural ties to build the Chinese nation’s sense of community, which invisibly influences and shapes the Chinese nation’s ideas.

Chinese characters record Chinese culture.

Characters are symbols of recording languages. Oracle Bone Inscriptions, the Shang Dynasty, is the earliest systematic and mature script in China, and has been able to record Chinese completely. As an original script, before Oracle Bone Inscriptions, Chinese characters had a long development process. Academic circles have been concerned about the formation and development of Chinese characters. When did Chinese characters finally form a system that can completely record the language? Meng Weizhi thought it was early summer, while Qiu Xigui thought it was the time of Xia and Shang Dynasties. The theory of "one series of three generations of characters" should be credible. Huang Dekuan once advocated that the characters in the late Shang Dynasty should be taken as a reliable starting point, and traced back to the early period, so as to make a reasonable speculation on the whole Chinese characters in the Shang Dynasty. This change from known to unknown is indeed a possible path to explore the formation and development of early Chinese characters.

The formation and development of Chinese characters are of great significance and must be explored in depth. According to the literature, "Cang Xie wrote a book, but it rained heavily, and ghosts cried at night" ("Huai Nan Zi Ben Jing Xun"). As for whether Cang Xie, the historian of the Yellow Emperor, created Chinese characters, we don’t need to delve into it, but the emergence of Chinese characters is indeed an earth-shattering and weeping feat. Chinese characters are super-epochal, which can cross the time barrier, record the long history of the Chinese nation and bear the civilization of the Chinese nation for 5,000 years. Chinese characters are super-regional, which can cross spatial boundaries and maintain information communication in different dialect areas of ethnic families, and people living in different regions can communicate smoothly.

"Thousands of years in ancient and modern times, tens of thousands of miles." Chinese characters break through the limitation of time and space and completely record and inherit Chinese culture. In front of countless Chinese sons and daughters, she is undoubtedly a long bond, firmly casting the Chinese nation community.

Chinese characters contain cultural mysteries.

"Every painting is learned." Observing each Chinese character statically, its glyph itself accumulates the profound mystery of Chinese culture. "The single body is a text, and the combination is a word." "Wen" is a single character, and the glyph itself cannot be divided; "Zi" is a combined character, and the glyph can be subdivided. Therefore, the word "Wen" can only be said, but the word "Zi" can be interpreted, and the name "Shuo Wen Jie Zi" is sincere. Xu Shen, known as "the ancestor of literate Sect", has long understood the mystery of "writing".

The older the Chinese characters, especially the pre-Qin characters such as Oracle Bone Inscriptions and Jinwen, the stronger their pictographic or ideographic elements, so they contain more cultural information of the word-making era. For example, the word "rainbow" of a rainbow is shaped like a [~ symbol ~] in Oracle Bone Inscriptions, which looks like two big worms winding down before and after. This is in line with the legend that the rainbow has two songs and can drink the water from rivers. It is recorded in Oracle Bone Inscriptions that "a rainbow comes from the north and drinks in the river" (Oracle Bone Inscriptions Collection 10405), to the effect that a rainbow comes out from the north and drinks in the river. The ancients could not give a scientific explanation for the natural phenomenon of rainbow in the sky, so they imagined it as a bug drinking water in a river. Later, the glyph evolved into a combined Chinese character. In Shuowen, it is a knowing word from insects to Shen (electricity), but most of the time it is a knowing word from insects, that is, the "rainbow" that is still in use today. However, in the silk script, there was once a glyph from the sound of rain workers. No matter from "Shen (electricity)" or "rain", it shows that the ancients have realized the relationship between rainbow and rain.

In fact, every Chinese character is a vivid existence of China culture. Through the typical Chinese character configuration related to human body, animals and plants, we can perceive the colorful world; Through the typical Chinese character configuration related to clothing, diet and living room, we can understand people’s basic necessities of life. Through the typical Chinese character configurations related to sacrifice, war and marriage, we can know people’s manners and customs. Through the typical Chinese character configuration related to national territory, land and clan, we can feel the feelings of Chinese sons and daughters about home and country.

The evolution of Chinese characters witnessed the cultural inheritance.

It is even more magical to observe Chinese characters dynamically. In the era of Oracle Bone Inscriptions, Chinese characters have entered a mature stage. Then, it went through bronze inscriptions, bamboo slips and silk books, seal characters and currency characters. From seal script to official script, from official script to official script, until today, simplified Chinese characters have been followed for thousands of years. In the meantime, although the form of Chinese characters has been constantly changing, its basic system has always been maintained, and its evolution can be clearly found.

Most of Oracle Bone Inscriptions in Shang Dynasty carved with a knife, and a few wrote with a brush. It is time-consuming and laborious to carve words on Oracle bones, so it is necessary to change the circle into a square, to fill in the outline, and to change the thick pen into a fine pen. The difference between writing carrier and tools will have a great influence on the font. In order to facilitate writing communication, Oracle Bone Inscriptions has been simplified. During the Spring and Autumn Period and the Warring States Period, the characters were abnormal, the vulgar style was popular, and the simplification was prominent, which was a reflection of the great changes in economy, politics and culture at that time. The change of seal script into official script is the most important change in the evolution of Chinese characters. It makes Chinese characters change from characters that need to be drawn with the body into simple characters composed of straight strokes, which greatly improves the writing speed and contributes to cultural communication.

Chinese character recording language contains culture, and each glyph has its own times. "One word is a cultural history." Rich cultural connotation indicates that every Chinese character is a treasure that needs our efforts to develop. Strengthening the interpretation of Chinese characters, digging deep into the historical, ideological and cultural connotation behind Chinese characters, and refining and displaying the essence of Chinese excellent traditional culture are not only the inevitable requirements for inheriting and developing Chinese excellent traditional culture, but also the proper meaning for enhancing the vitality and influence of Chinese culture. (Author: Qi Hangfu, deputy director of Chinese Character Civilization Center of Zhengzhou University)

Special feature of 1905 film network "Women also have thoughts, souls and ambitions. I have long been tired of everyone telling me that love is the only thing women should pursue."

　

As early as more than 100 years ago, Joe, played by Saoirse Ronan, made such a cry in the movie. This independence and persistence also inspired countless girls to break free and bravely pursue their hearts.

For women, work and career are not only the source of economic income, but also allow them to gain equality, respect, confidence and confidence while demonstrating their self-worth.

　

On the occasion of International Women’s Day, let Xiao Dianjun pay tribute to female workers from all walks of life through movies. "You work hard, really!"

　

Earn respect with dedication 　　　

　

During this special period, we got to know many ordinary and extraordinary female workers.

　

They are retrograde angels in white, fighting in the front line of anti-epidemic, bearing heavy work pressure but without complaint. They said: "The patient’s happy smile on his face when he was discharged from hospital made everything worthwhile."

　

The same is true of Lu Wenting, an ophthalmologist played by Pan Hong in the movie "Man to Middle Age".

At that time when medical talents were scarce, Dr. Lu was paid a meager salary of 56.5 yuan.However, she often has to face the pressure of working 24 hours a day, but she has no complaints and always puts the needs of patients first.

　

Under the long-term overload operation, Lu Wenting suddenly suffered from myocardial infarction and was dying. On the morning of her illness, she completed three operations in succession.

Lying on her deathbed, Lu Wenting recalled her life, and "curing the patient" became the most gratifying thing in her life:"Every time an eye is cured, it brings me great happiness. The most important part of my life belongs to you (patients)."

　

When she recovered and was discharged from the hospital, the door was full of her former patients, and I believe that was the happiest moment for doctors.

Nice da Silva, the hero of Nice Crazy Heart, is also a female doctor.She is a student of carl jung, a famous Swiss psychologist, and the only woman among the 158 graduates of Bahia Medical College that year.

　

In that era when female doctors were weak, she bravely stood up against the mainstream "inhuman" psychiatric treatments such as frontal lobectomy and electric shock, and advocated giving patients humanized care and guidance.

Nice teaches patients how to use canvases, paints and brushes, and works with dogs to treat mental patients.

　

Through colorful and unrestrained paintings, we can see the patients’ incomparably rich inner world and human dignity.

　　

"All chaos, madness and trauma need to be listened to and appeased."This is not "the benevolent heart of the doctor."

Educational moviesAdapted from a true story.

　

Lv Huihong, played by Miriam Yeung, was originally the principal of a prestigious school. She originally planned to retire early and travel around the world with her husband. However, a news that "suburban kindergartens are on the verge of closure and students are about to drop out of school" has aroused her heart of educating people.

Simple school conditions, only five students, plus a salary of 4,500 yuan, many people question that Lu Huihong is "putting on a show" and making a name for herself. However, she resolutely refused the advertising endorsement of the tutoring institution with an annual salary of 10 million yuan, and ran wholeheartedly for the five children.

　

She said to the students:"The headmaster’s dream is to be a good teacher, and he can stand at the school gate and wait for you to attend classes every day."

In reality, Lv Huihong is still the principal of Yuantian Kindergarten.

　

Under her hard work, in just five years, the number of students has increased from the initial five to as many as sixty, which has affected the fate of countless children and families.

　

This also fulfilled Lu Huihong’s initial intention of education."Being a teacher is doing a very meaningful thing and affecting life with life."

In the movieChinese and female journalist Sasha is a member of the "Focus" investigation team.

Together with her colleagues, she overcame many difficulties and exposed the dark side of church members’ long-term molestation of children and collusion between local forces.

　

In the face of threats and inducements from officials and the church, Sasha was humble and stuck to the responsibility and bottom line of journalists: digging the truth and reporting objectively.

Regardless of occupation, the dedicated and professional women in these films make us awe.

　

Break prejudice with strength 　　

　

In a special era, women should not only cope with work pressure in the workplace, but also always fight against discrimination and defend their hard-won right to work.

　

What happened to ruth bader ginsburg, the heroine of Gender-Oriented, is also a microcosm of the unequal treatment suffered by thousands of professional women in Qian Qian in the United States in the 1950s.

She graduated first in Harvard and Columbia Law School, but she couldn’t find a job as a lawyer.

　

The boss refused her for various reasons. "Female lawyers are too emotional." We hired a woman last year. "You are so beautiful that the wife of a male colleague will be jealous."

Although she had to put her dream of becoming a lawyer on hold, Ruth never gave up fighting for women’s rights and interests with the law.

　

Until the 1970s, when the social environment was mature, she began to challenge the unequal laws involving gender discrimination with one wonderful defense after another.And eventually became the first Jewish female federal supreme court justice in American history.

At the end of the film, she said hit the floor in court: "There are 178 laws concerning gender discrimination.This will be a thorn in our children’s future road. Our children are being turned away by various opportunities because of the so-called assumption of their abilities by the law …No matter how much effort it takes, we must amend these laws one by one. "

　　

At the same time as ruth bader ginsburg, there are such a group of women in the film. Although they are superior in IQ and ability, they have to endure double discrimination because of their "black+female" status.

It takes half a mile to run to the bathroom to find a toilet for people of color; If you want to participate in training and obtain the qualification of an engineer, you must first go to court and go to court; Because of skin color and gender, promotion and salary increase have been delayed.

Faced with these tangible and intangible discrimination, they chose to fight back with courage and strength, and proved that sentence with actions."NASA hired us not because we wore skirts, but because we wore glasses."

　

It is these pioneers’ struggles and efforts step by step that make women in the space system no longer "computers in skirts" but have the opportunity to walk to the stage and enjoy the applause and respect they deserve.

　　

Gender discrimination faced by Indian women is equally heavy. In the subconscious of many Indians, women are still the accessories of men, and they can get married at the age of 14 and teach their children for life.

　

But the father played by Aamir Hussain Khan chose a completely different path for his daughter. Despite the cynicism of the people around him, he insisted on letting his two daughters practice wrestling, and finally sent them to the podium of the international competition.

　

What he said to his daughter before the game made many people cry: "If you win tomorrow, it’s not your victory alone, but the victory won by thousands of girls. They are forced to be confined to housework, and the value of their lives is only to get married and have children.Tomorrow’s game is the most important game, because tomorrow you will play not only Australian players, but also all those who despise women! "

In the comment area of "Hidden People", there is a highly praised short comment that reads: "All the equality and not-so-equality we enjoy today are the result of the struggle of countless female predecessors. Never take what you have today for granted. "

　

This is the meaning of these films, and it is also the most touching place for this group of women.

　

Regain self-confidence with independence 　　　

　

Maybe we can’t be "heroines" who change history, but we can also gain respect and confidence through a job we love.

　

In the movie, Josie, the heroine played by Charlize Theron, decided to become a female miner in order to get rid of her abusive husband.

You know, at that time, the ratio of male to female employees in American coal mines was 30: 1. Female miners not only had to bear heavy physical labor, but also endured male harassment and social strange eyes.

　

But Josie never wanted to give up. After getting her first salary, she broke down in tears: "For the first time in my life, I can earn money by myself and support my children.For the first time in my life, I feel like I’m alive."

　

This is the meaning of work for Josie. She can stand up and stop swallowing her husband’s violence and give her children a better life with her own hands.

Nicole in the movie has a seemingly perfect life, but only she knows that in order to maintain her marriage, she has gradually become the "shadow" of her husband.

　

Forgetting her taste, dreams and pursuits, Nicole confided to the lawyer:"I have never lived for myself, just making him more and more glorious."

After waking up, Nicole chose to bid farewell to this marriage that made her lose herself. In Los Angeles, she finally realized her dream of directing and found a second life in Hollywood.

　

More importantly, she realized that what she really needed to get rid of was not the marriage relationship, but the self-contempt and self-limitation.

Little Women’s most touching passage is not the happy ending and the sad and tactful love, but Joe’s persistent running figure for getting closer to his dream every time.

When the publisher agreed to publish her story for the first time, when she organized her sisters to rehearse a play, when inspiration came in and she worked hard, Joe’s eyes sparkled and his face flushed with excitement became the most beautiful splendor of the film.

　

In today’s society, the physical obstacles faced by women in the workplace are decreasing, but the intangible prejudice still exists. Marriage and family are still important criteria for many people to measure women’s "success".

　

Maybe we can’t change society overnight, but at least try not to set limits on ourselves first. Every woman has the right to pursue happiness, but happiness means more than marriage and love.

　

Only in this way, when decades of marriage once broke down, can you calmly say, like Natalie, a professor played by Hupel,"My life has not completely failed. I have a full intellectual life, which is enough to make me happy."

Or like Aunt March, played by "Aunt Mei" in Little Women, proudly said:"I don’t need to get married, because I am a giant!"

Finally, I quote the speech delivered by the Nigerian writer Chimamanda Ngozi Adiqi at the graduation ceremony of Wesleyan College in 2015, and give it to every struggling girl and woman:

　

"We may not be able to change the world, but we can try and work together to make tangible and real efforts. At least we worked so hard.

　

Never use gender as a reason to do or not do something. Never, never do or give up anything because you are a woman. "

3.8 Exclusive film list

　

Little Women

Hidden characters

Nice Crazy Heart

Never give in

Lovely you

Gender-oriented

　

May all people, regardless of gender, draw warmth and strength from it!

Cctv newsOn the morning of June 8, the State Council Office held a press conference on "Implementing the Party’s 20 Major Decisions and Deploying and Promoting the Modernization of Emergency Management System and Capacity". Min Yiren, director of the Seismological Bureau of China, introduced at the meeting that at present, the national earthquake intensity quick report and early warning project has completed the main construction task, and 15,391 earthquake early warning stations, 3 national centers, 31 provincial centers and 173 prefecture-level information release centers have been built, forming a China earthquake early warning network composed of five systems: station observation, data processing, information service, communication network and technical support, and carrying out pilot services in Beijing, Tianjin and Hebei, Sichuan, Yunnan and Fujian. It is expected to be completed and accepted by the end of this year. After the project is put into operation, it will play a role in disaster reduction in the following aspects:

The first is to build a "first line of defense" for earthquake relief and reduce earthquake casualties. After the devastating earthquake, China Earthquake Early Warning Network will release earthquake early warning information through various channels such as emergency broadcast, mobile phone, TV, special terminal, etc., so as to provide users in the target area with early warning time of several seconds to dozens of seconds for emergency avoidance; After the earthquake, the distribution of the hardest hit areas can be quickly judged by measuring the measured earthquake intensity in a few minutes, which provides a scientific basis for the decision-making and deployment of earthquake relief. 6.2 seconds after the Luding M6.8 earthquake in Sichuan Province on September 5, 2022, China Earthquake Early Warning Network successfully released the early warning information, realizing the second-level early warning coverage for 1.5 million people in the epicenter and its surrounding areas.

The second is to "escort" lifeline projects and emergency disposal of major infrastructure. Relying on earthquake early warning terminals, emergency broadcasting and special communication lines, we will provide earthquake early warning information for the automatic emergency response of major strategic infrastructure such as high-speed railways, nuclear power plants, oil and gas pipelines and Gaoba reservoirs, and people’s livelihood infrastructure such as high-rise buildings, underground facilities and large-scale complexes, fill the gap in cross-industry earthquake emergency response services, promote the expansion of earthquake monitoring to earthquake disaster risk monitoring and prevention, and strengthen the ability of earthquake prevention and disaster reduction in the whole society.

The third is to provide strong support for earth science progress and international disaster reduction cooperation. Give full play to the advantages of building the world’s largest real-time transmission earthquake monitoring station network, provide high-quality scientific data information for promoting the innovative development of real-time seismology, real-time disaster science and earthquake engineering, and help the development and progress of earth science. At present, China’s earthquake early warning technology has gone abroad and been applied to the construction of Indonesian Jakarta-Bandung High-speed Railway. Seismological Bureau of China will give full play to its professional and technical advantages, better serve the country’s overall diplomacy, strengthen international cooperation in earthquake prevention and disaster reduction, and work together to reduce the risk of earthquake disasters.

In the next step, Seismological Bureau of China will continue to improve the construction of earthquake early warning network in China, continuously improve the safety, reliability and standardization of earthquake early warning service, expand the service field and efficiency, and provide more powerful earthquake safety guarantee for high-quality economic and social development.

This issue of the "Precision Frontier" column shared by Zhao Haitao’s research team published inGenome Medicine(IF =11.12) [1], a mutation signature was constructed and verified to predict the prognosis of patients receiving immunotherapy, and the potential immune response of different subtypes was studied by using multidimensional data.

Research background

Immunocheckpoint inhibitors (ICI) have changed the treatment of many cancers. However, the beneficiaries of ICI treatment are limited, so it is necessary to screen and predict biomarkers to classify patients. At present, many biomarkers, such as tumor mutation load (TMB), have been used as indicative biomarkers in clinic. However, some high TMB patients with gene mutation related to immunotherapy resistance are not sensitive to ICI treatment. Therefore, it is necessary to go beyond TMB and identify the specific genetic determinants of ICI treatment response.

research design

The study included genome and clinical data of 12,647 patients. There were 1572 cases in the training set (immunotherapy patients with 9 kinds of cancer) and 932 cases in the verification set (immunotherapy patients with 5 kinds of cancer). The training set was sequenced by MSK-IMPACT panel containing 468 genes.

The authors identified a set of 11 genes based on mutation, which can divide patients into high-risk and low-risk groups. The mutation of these 11 genes is related to the better response to ICI treatment, and this gene set has been proved to be an independent prognostic factor after ICI treatment.

research results

1. Identify mutant gene sets that can predict the outcome of immunotherapy.

Firstly, the survival differences of 468 genes in the training set were compared between wild type and mutant type, and 98 genes related to OS (global survival) were obtained. After that, LASSO COX regression analysis was further screened and 11 important genes were finally obtained. Through COX regression analysis, the risk score of each patient was quantified on the basis of 11 mutant gene sets. In the training concentration, the OS of patients in the high-risk group is shorter than that of patients in the low-risk group (Figure 1B). In order to study whether the gene set is limited to a specific population or suitable for different populations, the subgroup analysis regardless of age, drug use type and cancer species shows that the gene set is significantly related to the OS of patients treated with ICI (Figure 1C-E).

Figure 1. Generation and Verification of Gene Set Based on Mutation

2. Verification of predictable immunotherapy results

In order to further confirm the value of mutation-based gene set in predicting the results of immunotherapy, it was found that the OS of low-risk group was higher than that of high-risk group (Figure 1F). The research results of predicting ICI treatment response in gene set show that the DCB(durable clinical benefit) of ICI treatment in low-risk group is significantly increased compared with that in high-risk group (Figure 1G), and low-risk patients are more likely to respond to ICI treatment (Figure 1H). These results get the same results in the verification set (Figure 1I, J).

3. Gene set is an independent prognostic predictor of immunotherapy.

Next, the author verifies whether the gene set based on mutation is an independent predictor of immunotherapy response. In the training and validation set, univariate COX regression analysis showed that the gene set was related to OS. After adjusting for drug type, tumor type and TMB, multivariate COX regression analysis showed that the gene set was still an independent predictor, which confirmed the stability of its independent prediction of ICI prognosis (Figure 2A, B). In order to determine which factor has the best predictive performance, C-index is used to compare the performance of mutation-based gene sets with TMB and drug types. The results of C-index show that the gene set based on mutation can predict the prognosis more accurately than TMB and drug type in both training set and validation set (Figure 2C, D).

Fig. 2. Relationship between mutation-based gene sets and other characteristics

4. The clinical benefit of ICI treatment can be predicted based on the mutant gene set, disease stage, CTL and 6-IFN-g gene signature.

Considering the stage of disease, CTL and 6-gene IFN-g signature have been proved to be highly predictive of the response to ICI treatment, the authors speculate that they may play a synergistic role in predicting the response to immunotherapy. The author combined the gene set based on mutation with disease stage, CTL and 6-gene IFN-g signature through Nomotograph, and provided a method for clinicians to quantitatively predict the OS of patients treated by ICI. Fig. 2E is the nomogram of Riaz cohort construction, and the calibration curve of fig. 2F shows the consistency of actual and predicted results, indicating that these signature should be integrated into the predicted nomogram of ICI treatment.

5. Potential external immune landscape of high and low risk groups

In order to further explore the relationship between immune system and mutation-based gene set, the authors conducted a multi-group analysis of TCGA cohort, and the risk score divided TCGA cohort into high and low risk groups (Figure 3A). At the genome level, the proportion of white blood cells, lymphocytes and TIL in the low-risk group was significantly higher than that in the high-risk group (Figure 3B-D). The H&E staining results of TIL ratio are consistent with the above results (Figure 3E). In addition, the proportion of immunostimulatory cells (such as CD8 T cells) in the low-risk group is also significantly higher than that in the high-risk group (Figure 3F). The above results were further tested by Danaher et al.’ s immune infiltration score (figure 3G) and immune characteristic score (figure 3H), and it was found that the abundance of immune cells in low-risk group was higher. Then unsupervised clustering was used to cluster the immune characteristic scores of patients in TCGA cohort, and the results were clustered into two immune infiltration modes (Figure 3I), and the high immune infiltration was significantly enriched in the low-risk group (Figure 3J).

Fig. 3. Immune status of high and low risk population in TCGA cohort.

In addition, the immune signature in the low-risk group was significantly higher than that in the adjacent cancer tissue; On the contrary, the immune signature in the high-risk group was significantly lower than that in the adjacent tissues (Figure 4A). The correlation of immune activity in low-risk group was significantly higher than that in high-risk group (Figure 4B, C). GSEA results showed that 13 pathways were significantly enriched in the low-risk group, including 6 immune-related pathways, such as "cytotoxicity mediated by natural killer cells" (Figure 4D). Tumors in the low-risk group are associated with significantly higher CYT scores, and the number of fibroblasts in the high-risk group is now increasing (Figure 4E, F). According to these results, the low-risk group is rich in immune cells, which can respond to ICI treatment, and fibroblasts may help the high-risk group escape. The expression of chemokines in the low-risk group is higher (Figure 4G, H), so the author speculates that the enrichment of chemokines in the low-risk group may trigger an immune response.

Figure 4. Potential external immune landscape of high and low risk groups　

6. Potential inherent immune landscape of high and low risk groups

Some potential factors determining tumor immunogenicity between the two groups were compared. Mutation, new antigen load, TCR and BCR diversity in low-risk group were significantly higher than those in high-risk group, but CNV load and aneuploidy in high-risk group were higher than those in low-risk group (Figure 5A). This result is consistent with previous studies, that is, tumor aneuploidy is related to immunotherapy and decreased immune escape marker response. In addition, the heterogeneity of tumor in high-risk group is higher than that in low-risk group, which further supports the view that tumor will promote the development of heterogeneity in the presence of cytolytic activity and less active infiltration of immune cells. In order to further understand the mutation process of high and low risk groups, the mutation characteristics were described according to somatic mutation data, and four different mutation patterns were determined in TCGA cohort (Figure 5B). The frequency of these four mutation signals in the low-risk group is significantly higher than that in the high-risk group (Figure 5C). In addition, it was also found that immune checkpoint molecules (such as PD-1, PD-L1 and CTLA4) and costimulatory molecules were more highly expressed in the low-risk group (Figure 5E).

Figure 5. Potential innate immune response and escape landscape in high and low risk groups.　

7. Copy number characteristics of high and low risk groups

Significant differences in chromosome variation were detected in high and low risk groups (fig. 6A). Local amplification peaks of immune genes with good characteristics, such as PD-L1 (9p24.1) and PD-L2 (9p24.1), were observed in the low-risk group (fig. 6B, C). GO function annotation of the specifically amplified genes showed that the low-risk group was significantly enriched in two immune-related biological processes, while the high-risk group was significantly enriched in the biological process of "positive regulation of fibroblast proliferation", but not in any immune-related biological processes (Figure 6E). At the level of mRNA expression in TCGA cohort, the expression of PD-L1 and PD-L2 mRNA in low-risk group increased significantly (Figure 6G), which was consistent with CNV data. This finding suggests that CNVs in tumor contributes to the observed difference in immune infiltration.

Figure 6. Variation of copy number in high and low risk groups

discuss

This study is the first time to use an independent cohort to study the comprehensive mutant gene sets of different tumor types. Through PSM algorithm, hierarchical analysis and multivariate COX regression analysis, the application performance of mutation-based gene sets in different types of tumors was tested, and the results showed that mutation-based gene sets were reliable.

This study has the following innovation and practical application value. First, different types of tumors (such as NSCLC (non-small cell lung cancer), melanoma and renal cell carcinoma) are used, which represent the most common types of cancer treated with ICI. Secondly, the application of multiple biomarker prediction model needs to understand the factors that affect the accuracy and precision of Qualcomm analysis in clinical practice. The risk score formula and threshold of mRNA expression calculation are not suitable for verification with other types of data. Therefore, this study developed a gene set based on mutation to predict the clinical efficacy of ICI treatment. The composition of the above mutations is neither affected by tissue types nor adjusted by any other biomarkers. The risk score formula and threshold of gene set based on mutation can be verified by other tumor analysis methods, such as DNA sequencing and single nucleotide polymorphism microarray analysis. Therefore, mutation-based gene sets are not affected by technological changes, even when different platforms are used in different centers. Thirdly, in practice, gene sets based on mutations avoid exposing patients to potential immune-related adverse reactions when they are unlikely to respond, and enable patients to match to potentially more effective treatments more quickly. Fourthly, the prediction performance of gene set based on mutation is compared with other factors that can predict immunotherapy, and it is found that the prediction performance of gene set based on mutation is better than all these factors.

Several limitations of this study. First of all, because some mutations may be enriched in some tumor types, the initial goal of this study is to create a panel instead of identifying a single gene (such as BRAF), because the former can contain more genes to predict the prognosis of different types of tumors. Secondly, although the immune landscape of 11 genes in the gene set based on mutation has been explored, it is still necessary to clarify the molecular mechanism of each gene affecting immunotherapy in vivo and in vitro functional experiments. Thirdly, the enrichment scores of carcinogenic pathways and the expression patterns of immune checkpoints should also be detected by immunohistochemistry.

tag

The mutation-based gene set proposed in this study is the first comprehensive genomic marker systematically identified, which can be used to evaluate the ICI treatment effect of pan-cancer species. This study is also the largest prognostic model discovery project for cancer patients receiving ICI treatment (whether single drug treatment or combined treatment of anti-PD-1 and anti-CTLA-4). Nomoto, which combines mutation-based gene set with TMB and drug types, can help clinicians choose patients who may have a strong response to ICI treatment. In addition, it also reveals the different immune conditions of high and low risk groups, and specific genomic changes may drive the formation of these microenvironments. In a word, this work puts forward a new tumor classification method, which may guide the decision-making of ICI treatment.　END　

References:

[1]　Long, J., Wang, D., Wang, A. et al. A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape. G enome Med 14, 20 (2022). https://doi.org/10.1186/s13073-022-01024-y

Write Liu Hua Hua

Editing and typesetting SX

　　Xinhua Online Hai, August 14th (Reporter He Xinrong, Joline) The home is too messy, please ask someone to help you "break away"; Running at night, there are people who accompany the guidance; I can’t find bike-sharing when I go out, and someone will come and put it in a few days … … Have you ever thought that there are rich new job opportunities behind these increasingly familiar scenes?

　　It’s not that I don’t understand, it’s that the world is changing too fast. The surging new economy makes the definition of "work" richer and more exciting. More and more post-80s and post-90s have started different careers. While showing personality, it also brings more vitality to society.

　　The Magic of New Economy: From 360 Lines to 3600 Lines

　　Bike-sharing operator, shared office housekeeper, credit manager, quantitative trader, fashion blogger, family organizer, food stylist, escort runner, genetic tester, UP owner, drone trainer & HELIP; … The degree of "brain holes" in new occupations is beyond imagination.

　　Rome was not built in a day, and new occupations did not emerge overnight. The booming new economy in recent years is a fertile ground for these new occupations.

　　Although there is no accurate official definition, the coverage of "new economy" is very extensive. It not only refers to internet plus, Internet of Things, cloud computing and other emerging industries and formats in the tertiary industry, but also includes intelligent manufacturing and mass customization production in industry, and also involves family farms in the primary industry, and the integrated development of rural primary, secondary and tertiary industries.

　　In the past two years, the "new economy" has accelerated its growth, showing amazing "magic power": China’s employment indicators (including newly employed population, survey unemployment rate, etc.) rank first among 63 major economies in the world, while the macroeconomic growth rate is slowing down.

　　There is no doubt that the "new occupation" spawned by the "new economy" has absorbed a large number of employed people. The constantly updated list of national vocational qualifications shows that the number of jobs is moving from the original 360 to the new 3600. More and more people are creating new values for society while releasing their individuality.

　　Five rules of new career: see how many you have.

　　It is precisely because it resonates with the new economy at the same frequency that new occupations that look colorful actually have rules to follow. If you don’t want to be bound by the "cubicle", you may wish to refer to the following five rules:

　　[Internet Gene] The sharing economy has created operators, shared office housekeepers and shared house landlords in bike-sharing, while the platform economy has brought car drivers, couriers and take-away workers. Nowadays, most of the hottest entrepreneurial fields have Internet genes. With the Internet "connecting everything", people’s "career map" is being refreshed rapidly.

　　The current Internet applications are mainly concentrated in the fields of consumption and services. With the Internet becoming an infrastructure like hydropower and coal, and expanding to manufacturing and agriculture, new jobs with Internet genes will continue to emerge.

　　Su Hainan, vice president of china association for labour studies, said that the new occupation in the Internet era has some new features. If the task is fragmented, the working hours are not fixed; Diversified labor relations, such as the traditional employment relationship between platform and employees; Products and services are personalized, and labor output is more suitable for the specific needs of consumers.

　　[Subdivide and subdivide] A food can’t be nutritious, but it must be delicious. It’s not good just to eat, but to look good. As a result, the food stylist was born gorgeous. It must be said that the escalating demand of consumers has created new occupations in many seemingly inconspicuous segments.

　　"Professional people do professional things", with the east wind of consumption upgrading, new demands are constantly being stimulated: running and exercising with runners, traveling in personal tailor … … Because of China’s huge domestic demand market, any small demand may contain infinite potential.

　　[People behind "Nobody"] Unmanned driving, unmanned supermarket, drone delivery … … The rapid development of artificial intelligence technology makes the concept of "nobody" hot, and also makes many people worry that they will become a "useless" class. The statement that "50% of jobs will disappear in the next decade" has scared many fragile hearts.

　　In fact, no matter how developed artificial intelligence is and how many "unmanned" technologies are, there are still people behind it who are studying and manipulating it. However, their work changed from being in front of the stage to being behind the scenes. Tommy, Vice Minister of Science and Technology, said that in the long run, the employment brought by science and technology is far greater than unemployment. Take artificial intelligence for example, the algorithm engineer behind it is now in a state of extreme shortage. Instead of worrying about being replaced in the future, it is better to charge it now.

　　[Hobby is work] A few years ago, the old people would say, "Humor can’t be a meal", and no one regarded "telling jokes" as a job. Nowadays, "Duan Zishou" has really appeared. A few years ago, it was just a pastime to like the secondary culture and be good at making barrage videos. Today, the studio of "UP Master" has completed commercial realization in the real world of three dimensions.

　　Turning hobbies into jobs has become a new choice for many post-90s and post-90s. There are not so many instructions, and there is no strict index assessment. I do things with interest and "make money by playing." Therefore, parents who are eager to enroll their children in extracurricular training classes should see how important it is to respect their children’s nature and cultivate their interests!

　　[Rejuvenation of old crafts] It sounds that new occupations are often related to new knowledge and new skills? It’s not exactly like this. People always have some urgent needs, such as eating. From the ancient skilled worker to the modern chef, the professional "vest" is changing, but the core of pursuing delicious food has not changed.

　　Therefore, in the era of vigorous development of the new economy, the story of "rejuvenation of old crafts" has been staged again and again, even more moist than before. Bike-sharing is on fire, which has ruined the manufacturing workshop and the mechanic. There are fewer tailors on the street, but the old masters who come to order are popular. Once regarded as an unpopular veterinary graduate, she is now a pet beautician in MengMeng … … Society will not mistreat people with skills.

　　New employment concept: the boundary between white collar with gold collar and blue collar with gray collar is blurring.

　　The new economy gives birth to new occupations, and new occupations bring new employment concepts. In the past, people habitually divided their occupations into gold collar, white collar, gray collar and blue collar according to the working environment and income. Nowadays, more and more people find that the boundaries between these "collars" are becoming increasingly blurred.

　　"I earn 15,000 yuan a month. Will I lose this job for a gift of 2,000 yuan?" A few years ago, the story of a SF Express courier "getting angry" in a white-collar office was circulated around the Internet. Between words, full of professional pride. According to the traditional concept, the courier is a "blue-collar" position, which can make the courier stand at the scene of the bell ringing ceremony of listed companies due to the rapid growth of social demand and increasing technical content.

　　In the interview, the reporter was also exposed to many touching stories. Han Yien, a 28-year-old lawyer, was a financial company in Lujiazui, Shanghai. When she switched to be a home organizer, her mother cried. Because in the eyes of the older generation, this is a job of "serving people". But after more than two years of accumulation, Han Yien made a name for himself in the circle. Not only on-site service, but also receiving students and giving lectures, the "Qian Jing" is quite impressive. More and more elders gradually understand and recognize her choice of "not doing housework".

　　From farming society, industrial society, information society and intelligent age, the development of new technology has rapidly changed the traditional labor pattern. When mobile payment replaces cashier, artificial intelligence replaces repetitive workers, just as car drivers replaced coachmen.

　　It can be predicted that in the future, the social division of labor will become more and more detailed and the occupations will become more and more diversified. "Tall" jobs, such as investment bank traders, may be replaced by artificial intelligence if they don’t work hard. And more jobs without innate aura can live a wonderful life as long as they are willing to make sincere efforts.

　　The future has come. Embrace the new economy and fall in love with the new occupation. You, are you ready?

China Fund News reporter Yishan

On July 12th, Zotye Automobile, which has recorded 8 days and 5 boards, was exposed to double negative, which not only officially announced the termination of the 6 billion yuan fixed-income project, but also revealed that the company’s net profit in the first half of the year was expected to be negative.

According to the previous announcement, Zotye Automobile plans to issue no more than 1.521 billion shares (including the number) to specific targets, and raise no more than 6 billion yuan (including the number). The raised funds will be used for new energy intelligent networked automobile development and R&D capacity improvement projects, channel construction projects and supplementary liquidity.

As for the reason for the termination, Zotye Automobile said that it was a decision made after comprehensive consideration of the changes in the external market environment, the actual situation of the company, the controlling shareholder and the actual controller planning to change the actual controller of the company, and full communication with relevant parties such as intermediaries.

8 days and 5 boards! Since July, the share price has risen by over 52%.

On July 12, Zotye Automobile announced the abnormal fluctuation of stock trading. On July 11 and July 12, the deviation of the closing price of the company’s stock for two consecutive trading days was more than 20%, which was an abnormal fluctuation of stock trading according to the relevant regulations of Shenzhen Stock Exchange.

In fact, since July, Zotye Auto’s share price has risen sharply. As of the close of July 12, Zotye Auto reported 3.75 yuan per share, an increase of 9.97%. In the past eight trading days, it has recorded five daily limit boards, with an interval increase of over 52%. Once again, it has become the strongest "monster stock" in the recent new energy automobile sector.

In this abnormal fluctuation announcement, Zotye Automobile disclosed the relevant situation that the company paid attention to and verified.

First of all, after verification, the company found no need to correct or supplement the information disclosed in the previous period; No major undisclosed information that may or has had a great impact on the company’s stock trading price has been reported by the public media recently; Recently, the company’s operation is normal, and the internal and external operating environment has not changed significantly.

Secondly, Zotye Automobile said that the controlling shareholder and actual controller of the company are planning to change the actual controller of the company, and there are still uncertainties about when the planning to change the actual controller will be completed and whether it can be completed in the end. It is understood that at the end of May this year, Huang Jihong, the "white knight" who pulled the company back from the brink of bankruptcy, resigned as chairman for personal reasons. At the end of June, Zotye Automobile announced that the actual controller of the company may change.

Finally, it was in this announcement that Zotye Motor suddenly announced the termination of the 6 billion fixed-income fundraising.

The 6 billion fixed-income project suddenly ended.

According to the announcement previously issued by Zotye Automobile, the company plans to issue no more than 1.521 billion shares (including the number) to specific targets, and raise no more than 6 billion yuan (including the number). The raised funds will be used for the development of new energy intelligent networked vehicles and R&D capacity improvement projects, channel construction projects and supplementary liquidity.

On March 15th, Shenzhen Stock Exchange issued an inquiry letter, pointing out that the net assets attributable to the parent company at the end of the latest period were 3.025 billion yuan, and the total amount of funds raised this time was nearly twice that of the company at the end of the latest period. In addition, Zotye Auto is also required to explain the specific process of the new energy vehicle development project from research and development to official listing, and whether the company has the ability to develop new energy vehicles.

On May 9, the Shenzhen Stock Exchange issued a second round of inquiry letter, but since May 17, Zotye Automobile has disclosed nine delayed reply announcements. In the announcement on July 11, the company said that it would disclose the reply to the second round of audit inquiry letter before July 18.

However, at the fourth interim meeting of the Eighth Board of Directors in 2023, the Board of Directors of Zotye Automobile unanimously reviewed and approved the Proposal on the Company’s Termination of Issuance of A Shares to Specific Objects and Withdrawal of Application Documents. Decided to terminate the issue of A shares to specific targets in 2022, and applied to Shenzhen Stock Exchange to withdraw the application documents.

Regarding the reasons for the termination, Zotye Automobile said that since the company disclosed the plan to issue shares to specific targets, the company and relevant intermediaries have actively promoted related work. After comprehensively considering the changes in the external market environment, the actual situation of the company, the controlling shareholder and the actual controller planning to change the actual controller of the company and other factors, and after fully communicating with relevant parties such as intermediaries, the company decided to terminate the issue of shares to specific targets and withdraw the relevant application documents.

The risk of liquidity shortage remains.

After bankruptcy and reorganization, Zotye Auto successfully took off its hat in November last year, but it is not optimistic in terms of operating performance and asset status.

According to the financial report data, the company’s revenue declined year by year from 2018 to 2022. In 2018, the company’s revenue was still 14.764 billion yuan. By 2022, the company’s revenue was only 783 million yuan, and the company’s revenue shrank by over 94% in four years. In terms of net profit, the company has been losing money since 2019. Although the loss has narrowed, the net loss of the company has exceeded 23.6 billion yuan in the past four years. At the same time, Zotye Auto also revealed in the latest announcement that although the specific figures have not yet been counted, the company initially expects the net profit for the first half of 2023 to be negative.

By the end of 2022, the company’s net assets returned to its mother were 2.437 billion yuan, its total liabilities exceeded 4.6 billion yuan, and its ending cash balance was 116 million yuan. According to the company’s announcement, as of the end of the first quarter of this year, the company’s monetary funds were 922 million yuan, including 867 million yuan of restricted funds, and only 55.1074 million yuan of freely usable funds remained. This is obviously a drop in the bucket for a manufacturer with vehicle production qualification and Zotye Automobile, which will invest a lot of money in vehicle production and manufacturing in the future.

Zotye Auto also bluntly stated in the previous announcement that if the company’s external financing channels are not smooth, or the accounts receivable cannot be recovered on schedule or cannot be recovered, or the supplier fails to restore a reasonable credit period to the company for a long time, the company may face the risk of liquidity shortage, which will adversely affect the normal operation of the company.

In fact, due to the lack of liquidity, Zotye Automobile’s vehicle manufacturing almost came to a standstill in 2020 and 2021. In recent years, the company’s revenue mainly came from the sales of auto parts and door industry. Although the company has announced that it will gradually resume the whole vehicle business in 2022, and has completed the remodeling of core functional departments such as production, sales and research and development, it is not easy for Zotye to transform its new energy vehicles in the new energy vehicle market where the competition among new car-making forces such as Ideal, Weilai and Tucki is becoming increasingly fierce. In addition, as a vehicle manufacturer with an annual sales volume of more than 300,000 vehicles, Zotye Automobile sold only 502 vehicles in 2022.

In the previous increase specification, Zotye Automobile revealed that it will invest 5.037 billion yuan in the new energy intelligent networked vehicle development and research and development capability improvement project, including three parts: new energy intelligent networked vehicle development, common technology research and development and R&D center construction; In addition, 533 million yuan will be invested in channel construction projects. The company plans to build 216 self-operated stores in 100 cities including Beijing, Shanghai and Guangzhou in advance, covering major target markets and helping the company to quickly introduce new energy automobile products into the terminal consumer market.

According to the plan, if the above-mentioned 6 billion yuan fixed-income project finally lands, Zotye Automobile may be able to do a big job in the field of new energy vehicles. But now with the withdrawal of the fixed-income plan, where is the money for the company to build a car? Still a problem.

However, in the latest announcement, Zotye Automobile emphasized that all production and business activities of the company are proceeding normally at present, and the decision to terminate the fixed increase and withdraw the relevant application documents was made through full communication and careful analysis by the company’s management, intermediaries and other relevant parties. It will not have a significant adverse impact on the normal operation and sustained and stable development of the company, and there is no harm to the interests of the company and all shareholders, especially minority shareholders.

Wind data shows that as of July 10th, the total number of shareholders of Zotye Automobile reached 183,000, an increase of 34.56% compared with June 30th.

Editor: Huang Mei

Audit: Muyu

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Original title: "Billion car companies suddenly announced: termination! 》

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Cctv newsOn the afternoon of May 24th, Beijing held the 344th press conference on epidemic prevention and control to introduce the situation and answer questions from reporters. Wu Hao, head of the expert group of the community prevention and control group of the leading group for epidemic prevention and control in COVID-19, Beijing, gave epidemic prevention tips to the citizens when they went shopping in supermarkets, vegetable markets and other places. He said that supermarkets, vegetable markets and other public places are relatively closed, people are easy to gather, and there is a great risk of epidemic spread, which is the focus and difficulty of community epidemic prevention and control. In the past, many epidemics were spread and infected in these places.

It is necessary to strictly implement the epidemic prevention management in public places. Under the current situation that the social situation is not completely cleared, citizens should strictly do personal protection when going shopping, and prepare protective equipment such as masks and disinfectants. It is best to list the purchase list in advance and strictly control the number of people who go out to purchase. It is recommended that infants and the elderly try not to participate in shopping. Choose the nearest shopping spot, travel at the wrong peak, and try to avoid taking public transport. It is recommended to choose travel modes such as self-driving, cycling and walking.

When entering the vegetable market, supermarkets and other public places, you should cooperate with epidemic prevention measures such as temperature measurement and code inspection, wear a mask all the time, avoid pulling down the mask to communicate with the stall owner or taste food, and do not touch your eyes, mouth and nose directly with your hands. You should quickly select materials according to the list to minimize the stay time. Don’t go to the shelves and stalls where people gather, try to choose self-checkout and contactless payment to keep a safe social distance of more than one meter from others.

After purchasing, the used masks should be put into the relevant trash can, and hand disinfection should be done in time. If the packaging is suspected of being contaminated, disinfection should be done.