Finishing | Zhou Shuyi, Wangxiang
The "miracle drug" for lowering blood sugar is expected to reverse aging
Metformin is one of the most widely used oral hypoglycemic drugs in the world, which is not only safe, less adverse reactions, but also economical, and has become the first-line drug for the treatment of type 2 diabetes after more than 60 years of clinical practice. Interestingly, in recent years, metformin has been emerging with new effects: weight loss, cardiovascular protection, improvement of blood lipid metabolism, improvement of non-alcoholic fatty liver disease (NAFLD), treatment of polycystic ovary syndrome (PCOS), and even prevention and treatment of cancer.
A new study published in Cell on Sept. 12 has found new evidence for another potential efficacy of metformin: for the first time, the study has shown in primates that metformin can significantly slow down aging, especially in the brain cognitive function of older primates. This effect does not depend on its blood sugar regulating efficacy, but rather slows down cellular senescence by "resetting" the internal program of cellular senescence. Studies have shown that metformin can activate the transcription factor Nrf2 and enhance the antioxidant capacity of cells, promoting the rejuvenation of a variety of cells, including neurons.
The research team conducted a 40-month metformin intervention study on healthy middle-aged and elderly cynomolgus monkeys (equivalent to 40-50 years old in humans). Metformin, which is equivalent to the therapeutic dose of human diabetes, is administered daily and comprehensively evaluated through more than 60 indicators such as cognitive behavior, physiological function, medical imaging and blood testing. The results showed that long-term administration of metformin could effectively delay the aging of multiple organs such as liver, heart, lung, small intestine and skeletal muscle in primates, reduce periodontal bone loss and cerebral cortex atrophy, and significantly improve the cognitive function of elderly primates.
Given the long lifespan of primates, it is not technically feasible to assess the effects of aging interventions in terms of longevity and mortality alone. The researchers analyzed 11 systems and 79 tissues and organs of cynomolgus monkeys, and used machine learning models and multi-omics data to construct a multi-dimensional biological age "clock" of primate tissues and organs. The evaluation found that metformin can significantly reduce the DNA methylation age, gene transcription age and plasma protein age of primate multi-tissue organs, especially in the frontal lobe of the brain, and the reversal age can reach 6 years, which is equivalent to 18 years in humans.
The researchers said that the new study further proves that aging is a biologically analyzable, quantifiable and regulated process, and that the primate aging clock can be reversed through a single drug intervention, providing a new path for delaying the prevention and treatment of aging and related diseases. It is understood that the Chinese Academy of Sciences and Xuanwu Hospital of Capital Medical University have jointly carried out a "Phase II exploratory clinical study on metformin regulating the health of middle-aged and elderly people" to test whether oral metformin drugs can effectively intervene in aging in middle-aged and elderly men.
Related papers: https://doi.org/10.1016/j.cell.2024.08.021
"AI problem-solver" is coming, OpenAI releases a new generation of large model "o1"
On September 12, local time, artificial intelligence giant OpenAI officially released a new generation of large model "o1", and at the same time, a faster and lower-cost version of o1-mini was released. Compared to previous models, O1 has properties that are closer to those of humans: it can take longer to "think" and solve more complex natural science, programming, and math problems through deep reasoning. OpenAI said that the new model marks a milestone advancement in AI's complex inference capabilities, so the series codename was reset to "1". The o1 is internally codenamed "Strawberry" and is independent of the GPT model family, which is still in development.
What makes O1 special is that it is no longer purely through prompting to complete the chain of thought (CoT), but rather as a means of "thinking" and integrating it into the training and reasoning process. A chain of thought is a prompting method where the main idea is to encourage large models to explain their reasoning steps, leading to more accurate results. In the training phase, o1 uses reinforcement learning (RL) to better use the chain of thought to "think", which can break down complex problems into simple steps, identify and correct mistakes, and try different approaches. In the inference phase, the model introduces a longer internal chain of thought and takes longer to "think" about the problem. OpenAI says O1 performance will continue to improve as reinforcement learning time and thinking time increase. This opens up a new dimension in addition to the number of model parameters, dataset size, and computation of traditional model performance scaling laws.
By reading the chain of thought, it is possible to read the "heart" of the model and understand its thought process. However, the chain of thought is not aligned, and for factors such as user experience and maintaining a competitive advantage, O1 does not expose the original chain of thought to users, but only displays the summary generated by the model.
o1 excels in math, programming, and other tasks with high reasoning requirements, significantly ahead of GPT-4o. In the 2024 United States Invitational Mathematics Tournament (AIME), the average score rate of o1 is 74%, and GPT-4o is only 12%. If 1,000 samples are taken and weighted votes, O1 will get a score of 93%, ranking among the top 500 in the United States. In another test, o1 and GPT-4o each submitted anonymous responses to open-ended questions in different domains, with humans voting for their preferred answers. o1 is significantly better than GPT-4o in programming, data analysis, and mathematical calculations, and slightly inferior in writing and editing.
OpenAI scientist Noam Brown said that O1 is not perfect and sometimes even makes mistakes on simple problems, and many people have tried to prove with similar examples that "large language models can't reason", but O1 has made great strides in this area and can go further. Now, O1 needs to think for a few seconds; Future versions will not only be not fast, but will be slower – thinking for hours, days, or even weeks. "The cost of reasoning will go up, but how much are you willing to pay to develop a new anti-cancer drug? For a breakthrough battery? To prove the Riemann conjecture? AI can be more than just chatbots. ”
Official Profile: https://openai.com/index/introducing-openai-o1-preview/
The 2024 Funny Nobel Prize is revealed: the anus can breathe, the pigeon can open missiles, and the dead fish can swim
On September 12, local time, the 2024 "Ig Nobel Prize" was announced at the Massachusetts Institute of Technology (MIT) in United States. The Funny Nobel Prize is a playful parody of the Nobel Prize, established in 1991 by Marc Abrahams, editor of the Annals of Improbable Research, to recognize scientific achievements that "make people laugh and then provoke thought." The award-winning research includes 10 achievements, including "mammals can breathe in the anus", "observing the swimming ability of dead trout", and "pigeons firing missiles".
The chalkboard in Room 10, Building 250, MIT, where the award ceremony was held, and the chalk drawings were drawn live by artist Keira Lee Rice Ig Nobel Prize
Here is the full list of the "Funny Nobel Prizes" in 2024:
Physiology Prize: Many mammals were found to be able to breathe through the anus.
Japan researchers have found that mammals such as mice and pigs are able to "breathe" by absorbing oxygen from the rectum. Their experiments showed that perfusing the rectum with oxygen or oxygenated fluids could significantly increase blood oxygen levels in mammals, providing them with vital life support and reversing respiratory failure symptoms in mouse and pig models. They started the study during the pandemic, when many hospitals were desperately short of ventilators to support critically ill patients.
Related papers: doi.org/10.1016/j.medj.2021.04.004
Peace Prize: To explore the feasibility of placing live pigeons inside missiles to guide the missile's flight path.
Awarded to the late Professor Skinner, a famous psychologist in the United States, who taught pigeons how to fire missiles during World War II and had some success. But the project fell through to skepticism from United States military and government officials.
Related papers: psycnet.apa.org/doi/10.1037/h0045345
Physics Prize: Rainbow trout can also swim after death.
Awarded to Professor James · Liao of the University of Florida for conducting a comprehensive study of the swimming ability of dead rainbow trout. Under certain conditions, two staggered vortices will occur when air, water and other fluids bypass obstacles, a phenomenon known as "Carmen vortex street", which is very common in life. Rainbow trout are unique in that they like to linger around Carmen Vortex Street and swim in a distinctive "Carmen gait". This gesture is so effortless that even a dead fish can swim in the Carmen vortex and even swim upstream. "I found that live fish swim faster than dead fish, but not much faster, and a dead rainbow trout is dragged behind a stick and it also beats its tail to the rhythm of the current."
Related papers: doi.org/10.1242/jeb.01125
Botanical Prize: The discovery that certain real plants mimic the shape of neighboring artificial plastic plants.
Related papers: doi.org/10.1080%2F15592324.2021.1977530
Anatomy Prize: To study the effect of living in the northern and southern hemispheres on the direction of human hair rotation.
Related papers: doi.org/10.1016/j.jormas.2023.101664
Medical award: A placebo with a bit of burning side effects may be more effective.
Related papers: doi.org/10.1093/brain/awae132
Probability Award: Through theoretical analysis and 350757 experiments, it has been shown that when you flip a coin, the coin tends to land on the same side as before it was tossed.
Related papers: doi.org/10.48550/arXiv.2310.04153
Chemistry Prize: Chromatographic separation of drunk and sober worms.
Related papers: doi.org/10.1126/sciadv.abj7918
Demographics Prize: Finds that regions known for longevity tend to have poorly managed birth and death records, and pension fraud is rife.
Related papers: doi.org/10.1101/704080;doi.org/10.1101/704080
Biology Award: Have a cat stand on the back of a cow and scare the cow by blowing up a paper bag next to it to explore the factors that affect cow lactation.
Related papers: doi.org/10.1093/ansci/1939.1.80
United States amateur astronauts complete the world's first commercial spacewalk
At about 6 o'clock Eastern time (6 p.m. Beijing time) on September 12, the two crew members of the United States "Polaris Dawn" space mission began to take turns to go out of the capsule, which was the world's first commercial spacewalk by a non-professional astronaut.United States The Polaris Dawn mission team consists of four non-professional astronauts. They were launched from the Kennedy Space Center in Florida on the 10th aboard the Dragon spacecraft for a multi-day space trip.
贾里德·艾萨克曼成功出仓。| PolarisProgram
The spacewalk mission was carried out by Jared · Isaacman, founder and CEO of United States payment service Shift4 Payments, 41, and Sara · Gillis, an engineer at SpaceX. SpaceX's live broadcast on social media X showed that the spacecraft was in orbit at an altitude of 732.2 kilometers above the ground, and the out-of-cabin activities officially began at 6:12 Eastern Time (18:12 Beijing time) on the 12th of United States Eastern Time.
For safety reasons, the two kept one hand or foot on a ladder-like support structure at the hatch of the spacecraft at all times during their stay outside the spacecraft, and a 3.6-meter cable connected them to the spacecraft. Two other crew members, Kid · Portit and Anna · Menon, monitored the entire cabin, and they also wore the company's designed extravehicular activity spacesuits during the mission, as the entire cabin was in a depressurized environment. The entire mission, including procedures such as safety checks and repressurization of the ship's holds, lasted approximately two hours.
The Polaris Dawn mission is co-funded by Isaacman and SpaceX. The mission team has conducted a series of scientific research and experiments, including testing the communication between the spacecraft and the Starlink satellite, and studying the effects of space flight and space radiation on human health. (CCTV News)
United States men use AI to make hundreds of thousands of fake songs
The New York Times reported on September 5 that a man in North Carolina, United States, was accused of using artificial intelligence (AI) to produce hundreds of thousands of songs using artificial intelligence (AI) to fake the name of the band, upload them to streaming music platforms, and manipulate the robot "water army" to brush the number of plays. Although each broadcast can only be exchanged for a meager royalty income, it adds up, and he has accumulated more than 10 million US dollars at the time of the East Window incident.
According to the report, the man's name is Michael · (Michael Smith), 52 years old, and he was originally a musician who drank the northwest wind. In 2018, he partnered with the CEO of an AI music company to release thousands of AI-produced songs, and painstakingly made up song titles, bands, and composers to stream to earn a share. For example, the titles of the songs are "Zygotic Washstands", "Zymotechnical", and "Zygophyllum", which are written by "Callous Post", "Calorie Screams", "Calvinistic Dust", etc. But in reality, they have neither skill nor emotion, they are all AI.
In an email in February, Mr. Smith boasted that his songs had been played 4 billion times since 2019 and that he had earned $12 million in royalties.
In October 2018, a company notified Smith that it had received "multiple reports of streaming abuse" and was preparing to remove his songs from all platforms. Smith flatly denied: "Absolutely impossible! Absurd! Conscience of heaven and earth! How to go through the legal channels? Today, Smith faces multiple charges, including wire fraud and conspiracy to launder money.
A new breakthrough has been made in the continental reusable rocket
According to Xinhua News Agency, on the afternoon of September 11, the mainland's self-developed Suzaku No. 3 VTVL-1 reusable vertical take-off and landing recovery test rocket completed a 10-kilometer vertical take-off and landing return flight test at the Jiuquan Satellite Launch Center, marking a breakthrough in the mainland's commercial aerospace reusable launch vehicle technology, and taking a key step towards achieving large-capacity, low-cost, high-frequency, and reusable space launches in the future.
This mission is the first time in China to realize the secondary ignition of vertical take-off and landing return rockets in the air, the joint guidance control of "grid rudder-air-conditioning attitude control-engine" in the transonic high dynamic pressure environment, and the engineering application of real-time wind repair technology in high-altitude wind. The test went through the process of "ascent-engine shutdown-unpowered taxiing-engine secondary start in the air-soft landing", and all indicators met the expected design.
According to Blue Arrow aerospace experts, the test rocket is a single-stage liquid oxygen methane rocket, with a diameter of 3.35 meters, a length of 18.3 meters, a take-off mass of about 68 tons, a take-off thrust of 800 kN, equipped with 3 sets of landing buffer legs, a new 4-piece grid rudder system, and a high-strength stainless steel rocket body structure consistent with the Zhuque 3 rocket; to 111% variable thrust adjustment and multiple ignition capability.
The test arrow of this mission is an engineering prototype built with a full-scale engine, which is an important part of the engineering development of the Blue Arrow aerospace reusable rocket. Through two VTOL recovery tests, the model team successfully verified a number of key technologies for reusable rockets, laying the foundation for the future first flight and recovery of Suzaku III.
Dry eyes, astringent eyes? Smile, the effect is comparable to eye drops
Laughter is an expression, which varies from person to person. Not only that, but a study published in The BMJ on September 11 showed that laughter is still a good medicine: "laughter exercise" is as effective as artificial tears (0.1% sodium hyaluronate) for dry eyes. This suggests that laughter may be an effective, safe, low-cost, and environmentally friendly intervention that can be used as a first-line treatment for dry eye.
Dry eye is one of the most common eye diseases, and its main symptoms include dry eyes, astringent eyes, foreign body sensation, etc., which seriously affect the vision and quality of life of patients. Recent studies have suggested that dry eye is a lifestyle-related disease that is closely linked to psychological states such as depression and anxiety. Through clinical observation, the research team found that "laughter training" can not only alleviate anxiety and depression, but also improve the symptoms of eye discomfort in dry eyes.
To further understand the therapeutic effect of "laughter training" on dry eye, the investigators conducted a prospective, non-inferiority randomized controlled clinical study. The study included 299 eligible patients with symptomatic dry eye who were randomized into 2 groups, one of which was 150 people, who were treated with conventional artificial tears (i.e., sodium hyaluronate at a concentration of 0.1%); Another group of 149 people conducted "laughter training" and recorded the intervention throughout the process.
In the study, "laughing training" is a set of passwords, designed by the research team based on facial and eye muscle movements, and the patient repeats the sound according to the password to form an exaggerated expression, so as to simulate the state of laughter, 30 times of the password is 1 training, 4 times a day. The content of the password: "hihihi (pinyin spelling), hahaha, eggplant eggplant, eggplant, seven joys, seven joys, seven joys, hahahahahaha".
The results showed that after 8 weeks of intervention, patients in both the "laugh training" group and the artificial tears group had improved symptoms and ocular signs. In the primary outcome measure, the ocular surface disease index, a measure of the subjective severity of dry eye, was no less effective in the "laughing training" group than the artificial tears group, and even better than the artificial tears group in some improvements in ocular signs.
Liang Lingyi, the leader of the research project and deputy director of the Zhongshan Eye Center of Sun Yat-sen University, said that the study confirmed the effect of "laughter training" on the treatment of dry eye patients, and proposed an effective, safe, low-cost and environmentally friendly non-drug treatment from a new perspective. "Laughter training" may improve the stability of the tear film and the function of the meibomian glands, and the research team is conducting further research on the relevant biological mechanisms.
Related papers: https://www.bmj.com/content/386/bmj-2024-080474
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