Mott Corp.

COVERLipid droplet growth is orchestrated by the seipin complex, which provides a structural platform for droplet nucleation and expansion. The microprotein adipogenin fine-tunes seipin’s conformation, remodeling its architecture to regulate lipid storage capacity. This modulation results in the formation of fewer but larger lipid droplets, revealing a key mechanism in lipid homeostasis. 封面文章指出，脂滴的生长由 seipin 复合物调控，该复合物为脂滴的成核和扩张提供结构平台。微蛋白 adipogenin 能够精细调节 seipin 的构象，重塑其结构以调控脂质储存能力。这种调节导致脂滴数量减少但体积增大，揭示了脂质稳态的关键机制。参见第 570 页和 eadr9755 。 Illustration: C. Bickel/Science; Data: C. Li et al., Science 390, eadr9755 (2025).Editorial  社论Advancing research on financial stability and climate-related financial risk推进金融稳定和气候相关金融风险方面的研究 Biomedical philanthropy promises dramatic expansion and AI focus生物医学慈善事业有望大幅扩张并聚焦人工智能。 Entering its second decade, the Chan Zuckerberg Initiative will make science the core mission for its founders’ billions进入第二个十年，陈·扎克伯格基金会将把科学作为其创始人数十亿美元捐赠的核心使命。 As the promise of artificial intelligence (AI) captivates biomedicine, few people are riding the wave like Priscilla Chan—because few people have her resources. Trained as a pediatrician, Chan and her husband, Facebook creator Mark Zuckerberg, co-run a philanthropy that launched in 2015 with the wildly ambitious—some would say quixotic—goal of curing, preventing, or managing every disease by the end of the century. The couple pledged nearly their entire fortune—$45 billion then and more than $200 billion today—to the Chan Zuckerberg Initiative (CZI), which would also support their education and progressive causes.随着人工智能（AI）的潜力吸引着生物医学领域的目光，很少有人能像普莉希拉·陈（Priscilla Chan）那样乘风破浪——因为很少有人拥有她那样的资源。陈是一位儿科医生，她和丈夫、Facebook 创始人马克·扎克伯格（Mark Zuckerberg）共同运营着一家慈善机构。该机构于 2015 年启动， 其目标雄心勃勃——有些人甚至认为是异想天开——即在本世纪末治愈、预防或控制所有疾病。这对夫妇承诺将他们几乎全部的财富——当时的 450 亿美元，如今已超过 2000 亿美元——投入到陈·扎克伯格倡议（Chan Zuckerberg Initiative，简称 CZI）中，该机构还将支持他们的教育事业和进步事业。 Recently, however, the foundation has wound down support for almost everything but science. And this week, CZI announced it is increasing its research spending, doubling down on AI, and vowing to meet Chan and Zuckerberg’s biomedical goal even earlier—although CZI won’t set a specific target. “As I get older, the faster I personally want it to be,” says Chan, 40, sitting in her modest office at CZI’s headquarters in Redwood City, California. “It really feels like we’re at a moment where there’s a lot that can be done to accelerate the pace of scientific discovery.”然而，最近该基金会几乎停止了对除科学以外的所有领域的资助。本周，CZI 宣布将增加研究经费，加大对人工智能的投入，并承诺更早地实现陈和扎克伯格的生物医学目标——尽管 CZI 并未设定具体目标。“随着年龄增长，我个人越希望进展更快，”40 岁的陈坐在位于加州红木城 CZI 总部的一间简朴办公室里说道，“我们感觉现在正处于一个可以加速科学发现进程的关键时刻。” As the CEO of Meta—which includes Facebook, Instagram, and WhatsApp—Zuckerberg owns nearly 15% of the company, and his wealth can shift by tens of billions in a day with the fluctuations in his stock holdings. But the couple’s plan to donate 99% of their Meta shares to CZI means its wealth could eclipse that of established titans of biomedical philanthropy, including the Howard Hughes Medical Institute (HHMI) and foundations run by Gates, Wellcome, and Novo Nordisk (see table, below). “It’s fantastic,” says Robert Tjian, a biochemist at the University of California (UC), Berkeley who once led HHMI and has been a scientific adviser to CZI. “There are a lot of other very, very wealthy individuals that are not doing it.”作为 Meta 集团（旗下拥有 Facebook、Instagram 和 WhatsApp）的首席执行官，扎克伯格持有该公司近 15%的股份，其财富会随着股票持有量的波动而一天之内变动数百亿美元。但这对夫妇计划将他们持有的 99%的 Meta 股份捐赠给 CZI，这意味着 CZI 的财富可能会超过一些老牌生物医学慈善巨头，包括霍华德·休斯医学研究所（HHMI）以及盖茨基金会、惠康基金会和诺和诺德基金会（见下表）。“这太棒了，”加州大学伯克利分校的生物化学家罗伯特·蒂安说道，他曾领导 HHMI，并担任 CZI 的科学顾问。“还有很多其他非常非常富有的人没有这样做。” CZI now says it will spend at least $10 billion on basic scientific research over the next decade, more than twice the $4 billion it spent in its first decade, and on par with the annual spending of HHMI. Abundant optimism about marrying AI and biology has also led CZI to drop the softer “managing disease” part of its mission, and Chan says if the couple sees further opportunities to fulfill the cure and prevention vision, they’ll cash in more stocks. “We’re ready to spend,” she says.CZI 现在表示，未来十年将在基础科学研究方面投入至少 100 亿美元，是其成立第一个十年 40 亿美元投入的两倍多，与霍华德·休斯医学研究所（HHMI）的年度支出持平。对人工智能与生物学相结合的乐观态度也促使 CZI 放弃了其使命中较为温和的“疾病管理”部分。陈女士表示，如果他们看到更多实现治愈和预防愿景的机会，他们将出售更多股票。“我们已经准备好投入资金了，”她说。 One new project already benefiting from their generosity—and spelled out in a preprint this week—is a major AI effort to build a virtual version of the human immune system that could speed the hunt for new therapies. In another sign of its bet on AI, CZI this week announced its new head of science will be a computer scientist, Alex Rives of the Broad Institute of MIT and Harvard, who has developed large language models for biology and was a former AI researcher at Facebook.一项已受益于他们慷慨资助的新项目—— 本周在一篇预印本中详细阐述——是一项旨在构建人类免疫系统虚拟版本的重大人工智能项目，有望加速新疗法的研发。CZI 本周宣布其新任科学主管将由计算机科学家 Alex Rives 担任，他来自麻省理工学院和哈佛大学博德研究所，曾开发过用于生物学的大型语言模型，也曾在 Facebook 担任人工智能研究员，这再次表明了他们对人工智能的重视。 In CZI’s first decade it invested $3.5 billion on social advocacy, education, and politics. But according to an open letter sent to employees in February from the chief operating officer, CZI over the past few years shifted away from those issues to “align with our focus as a science philanthropy” and because of “the current legal and policy landscape.” The letter also noted that CZI was cutting its own diversity, equity, inclusion, and accessibility team.在 CZI 成立的第一个十年里，它投入了 35 亿美元用于社会倡导、教育和政治活动。但根据首席运营官二月份发给员工的一封公开信 ，CZI 在过去几年里逐渐减少了对这些领域的投入，以“符合我们作为科学慈善机构的定位”，同时也是因为“当前的法律和政策环境”。这封信还指出，CZI 正在裁撤其多元化、公平、包容和无障碍团队。 These moves have drawn sharp criticism from some former CZI employees and jilted grantees. And scientists inside and outside of CZI were taken aback by Zuckerberg’s recent effort to curry favor with President Donald Trump through a $1 million donation from Meta to his inaugural celebration. Matthew Porteus, a pediatrician at Stanford University, questions Zuckerberg’s support for a president who wants to reduce the National Institutes of Health budget by 37%. “There’s an inconsistency between what the CZI is doing and what is going on at the federal government level,” says Porteus, who previously received funding from the philanthropy.这些举措招致了一些前 CZI 员工和被拒资助者的强烈批评 。扎克伯格最近通过 Meta 向特朗普总统的就职典礼捐赠 100 万美元，试图讨好特朗普，这一举动令 CZI 内外的科学家们都感到震惊。斯坦福大学儿科医生马修·波特厄斯质疑扎克伯格支持一位想要削减美国国立卫生研究院 37%预算的总统。“CZI 的所作所为与联邦政府的政策存在矛盾，”波特厄斯说道，他此前曾接受过该慈善机构的资助。 Cori Bargmann, a cell biologist at Rockefeller University who was CZI’s head of science for its first 6 years and remains an adviser, says she knew when she came on board that Zuckerberg had to wear two hats. “It’s a lot easier to do philanthropy when you’re not trying to run a major business at the same time, especially one that has large-scale implications in terms of the political process and how it interacts with it and the legal system,” Bargmann says. She recounts that when she took the CZI job in 2016, HHMI head Erin O’Shea offered a warning. “She said, ‘I just want you to know that my job is easier than your job, because Howard Hughes is dead.’”科里·巴格曼是洛克菲勒大学的细胞生物学家，曾担任扎克伯格研究所（CZI）前六年的科学主管，目前仍是该研究所的顾问。她说，她加入 CZI 时就知道扎克伯格必须身兼两职。“当你不用同时运营一家大型企业时，做慈善就容易得多，尤其是一家对政治进程及其与法律体系的互动有着重大影响的企业，”巴格曼说。她回忆起 2016 年她加入 CZI 时，霍华德·休斯医学研究所（HHMI）所长艾琳·奥谢曾警告她：“她说，‘我只想让你知道，我的工作比你的轻松，因为霍华德·休斯已经去世了。’” Chan says she focuses on what she can control. “I have the ability to influence and be a steady funder and to show up for our scientists … and move science forward.”陈女士表示，她专注于自己能够掌控的事情。“我有能力施加影响，成为稳定的资金提供者，支持我们的科学家……并推动科学进步。” In its first decade, CZI funded more than 250 university investigators like Porteus, issued 2000 grants, and trained scientists in dozens of countries. It also hired more than 150 full-time scientists and other staff for “biohubs” in San Francisco, New York City, and Chicago, bringing together diverse specialties that traditionally didn’t collaborate much. An imaging institute in Redwood City that will receive $600 million over 10 years develops state-of-the-art microscopes and software to help the biohub network clarify the workings of cells. Undergirding all of these efforts is an open science ethos that allows outside scientists to adopt and modify CZI software and algorithms.在成立的第一个十年里，CZI 资助了超过 250 位像 Porteus 这样的大学研究人员，发放了 2000 多项科研经费，并在数十个国家培训了科学家。它还在旧金山、纽约和芝加哥的“生物中心”聘请了 150 多名全职科学家和其他工作人员，将传统上合作较少的不同专业领域聚集在一起。位于红木城的一家成像研究所将在未来十年获得 6 亿美元的资助，用于开发最先进的显微镜和软件，以帮助生物中心网络阐明细胞的运作机制。所有这些努力都建立在开放科学的理念之上，允许外部科学家采用和修改 CZI 的软件和算法。 Among the projects CZI supported is an international effort called the Human Cell Atlas, dubbed the Google map of the body, that attempts to chart all cell types across the human life span. A consortium led by Stanford biophysicist Steve Quake at the San Francisco biohub created another atlas cataloging more than 1 million cells from 28 human organs and charting how they interact with each other, and a project led by biochemist Joe DeRisi of UC San Francisco taught researchers in low- and middle-income countries to detect and track infectious diseases.CZI 支持的项目包括一项名为“ 人类细胞图谱” 的国际合作项目，该项目被誉为“人体谷歌地图”，旨在绘制人类生命周期中所有细胞类型的分布图。由斯坦福大学生物物理学家史蒂夫·奎克(Steve Quake) 领导的旧金山生物中心团队创建了另一张图谱，收录了来自 28 个人体器官的超过 100 万个细胞，并绘制了它们之间的相互作用图谱。此外，由加州大学旧金山分校生物化学家乔·德里西(Joe DeRisi) 领导的一个项目则致力于帮助中低收入国家的研究人员检测和追踪传染病。 CZI in 2019 began to fund a network of patient-led organizations that focus on rare diseases. In July, it announced its first investment in a treatment-related project: $20 million over 3 years to UC San Francisco and UC Berkeley to test personalized CRISPR treatments for eight children with severe genetic immune diseases. The goal is to extend the gene-editing success reported earlier this year for “Baby KJ,” who had a rare metabolic disease. “They’ve accomplished a lot, but it’s still early in many ways,” Tjian says. “They’re taking on a really powerful challenge and trying many things.”2019 年，CZI 开始资助一个由患者主导的组织网络，这些组织专注于罕见病领域。今年 7 月，CZI 宣布了其首笔与治疗相关的项目投资：向加州大学旧金山分校和加州大学伯克利分校提供 2000 万美元，为期三年，用于测试针对八名患有严重遗传性免疫疾病儿童的个性化 CRISPR 疗法 。该项目的目标是延续今年早些时候报道的基因编辑疗法在“KJ 宝宝”（患有罕见代谢疾病）身上取得的成功。“他们已经取得了很大的成就，但在很多方面仍处于起步阶段，”Tjian 说道，“他们正在迎接一项非常艰巨的挑战，并尝试多种方法。” CZI is rebranding its three original labs and the imaging center as Biohub, a single entity that Rives will oversee and a reflection of its plan to have everyone share data to create the virtual immune system. Staff at the San Francisco biohub and CZI’s imaging institute will also all move to a massive new building in Redwood City in 2027. “It’s an opportunity to bring people together that normally would have a hard time talking or interacting,” says immunologist Matthias Haury, chief operating officer of that biohub and the imaging institute. A chunk of increased investment will go toward a 10-fold boost over the next 3 years in computing power for Biohub investigators.CZI 正将其原有的三个实验室和影像中心重新命名为 Biohub ，这是一个由 Rives 负责管理的单一实体，体现了其让所有人共享数据以构建虚拟免疫系统的计划。旧金山生物中心和 CZI 影像研究所的员工也将于 2027 年全部迁至红木城一座全新的大型办公大楼。“这是一个让那些通常难以沟通或互动的人们聚集在一起的机会，”生物中心和影像研究所的首席运营官、免疫学家 Matthias Haury 说道。新增投资的一部分将用于在未来三年内将 Biohub 研究人员的计算能力提升十倍。 Further supporting the effort to make a virtual immune system, biophysicist Andrea Califano leads a group at the New York City biohub that genetically modifies immune cells to explore how they move from one state of activity to another or migrate to sites around the body. By the end of next year, the group aims to perturb about 100 million single cells and record the changes. “We want to start creating mechanisms that allow us to study the immune system as a system,” Califano says.为了进一步支持构建虚拟免疫系统的努力，生物物理学家安德烈亚·卡利法诺（Andrea Califano）领导着纽约生物中心的一个团队，该团队通过基因改造免疫细胞，探索它们如何从一种活性状态转变为另一种活性状态，以及如何迁移到体内各处。到明年年底，该团队的目标是扰动约 1 亿个单细胞并记录其变化。“我们希望开始创建一些机制，使我们能够将免疫系统作为一个系统来研究，”卡利法诺说。 The Chicago biohub is pumping massive amounts of data into the project as well, by probing inflammation in organ-mimicking, lab-grown blobs of tissues known as organoids. The group develops sensors—described in a Science paper last year—that every hour sample organoids for protein and metabolic changes that cause psoriasis and inflammatory bowel diseases.芝加哥生物中心也正通过探测类器官（一种模拟器官的实验室培养组织）中的炎症反应，向该项目投入大量数据。该团队开发了一种传感器 （去年发表在 《科学》 杂志上的一篇论文中有所描述），该传感器每小时对类器官进行采样，检测导致银屑病和炎症性肠病的蛋白质和代谢变化。 Veteran immunologist Jeffrey Bluestone, who now heads Sonoma Biotherapeutics, remains skeptical that CZI’s virtual immune system will be the key to curing and preventing all diseases. “It ain’t going to work,” he says. But he says the project could still be “transformational” for immunology, answering questions such as which cells are affected by a flu virus infection and ways to improve the vaccine for the pathogen.资深免疫学家杰弗里·布鲁斯通（Jeffrey Bluestone）目前担任索诺玛生物治疗公司（Sonoma Biotherapeutics）的负责人，但他仍然怀疑 CZI 的虚拟免疫系统能否成为治愈和预防所有疾病的关键。“这行不通，”他说。但他认为，该项目仍然可能对免疫学产生“变革性”影响，解答诸如哪些细胞会受到流感病毒感染以及如何改进针对该病原体的疫苗等问题。 Chan says if AI delivers on its promise and reveals pathways to make novel medicines, CZI may tilt more toward clinical research. She and Zuckerberg are now parents of three daughters, the oldest born the year CZI launched. “It feels more urgent” to push CZI toward its ambitious goals, Chan says. “People need hope. I want to believe that impossible things are possible.”陈女士表示，如果人工智能能够兑现承诺，揭示研发新型药物的途径，CZI 可能会将重心更多地放在临床研究上。她和扎克伯格现在育有三个女儿，大女儿出生于 CZI 成立的那一年。“推动 CZI 实现其宏伟目标，感觉更加紧迫了，”陈女士说。“人们需要希望。我希望相信，不可能的事情也能成为可能。” Tree rings from ancient coffins offer clues to Earth’s past古代棺材上的树木年轮为了解地球的过去提供了线索。 Wood from gravesites can help reconstruct historic temperatures, droughts, and floods墓地出土的木材可以帮助重建历史上的气温、干旱和洪水情况。Thinning of DOE advisory bodies dismays researchers美国能源部咨询机构人员精简令研究人员感到沮丧 Department of Energy scraps committees that served as conduits to distinct research communities美国能源部解散了曾作为不同研究团体沟通渠道的委员会。Antarctic glacier’s retreat is fastest in modern history南极冰川的消融速度是现代史上最快的。 Tides and glacial earthquakes caused record ice loss at Hektoria Glacier潮汐和冰川地震导致赫克托里亚冰川冰量损失创历史新高AI hallucinates because it’s trained to fake it till it makes it人工智能会产生幻觉，因为它被训练成不断伪装直到成功。 Teaching chatbots to say “I don’t know” could curb falsehoods but harm business model教会聊天机器人说“我不知道”或许能减少虚假信息，但会损害商业模式。 Earlier today, OpenAI completed a controversial restructuring of its for-profit arm into a public benefit corporation: the latest gust in a whirlwind that has swept up hundreds of billions of dollars of global investment for artificial intelligence (AI) tools.今天早些时候，OpenAI 完成了对其营利性部门的重组，将其转变为一家公益公司，这一举措引发了争议：这是席卷全球数千亿美元人工智能 (AI) 工具投资的旋风中的最新一波。 But even as the AI company—founded as a nonprofit, now valued at $500 billion—completes its long-awaited restructuring, a nagging issue with its core offering remains unresolved: hallucinations. Large language models (LLMs) such as those that underpin OpenAI’s popular ChatGPT platform are prone to confidently spouting factually incorrect statements. These blips are often attributed to bad input data, but in a preprint posted last month, a team from OpenAI and the Georgia Institute of Technology proves that even with flawless training data, LLMs can never be all-knowing—in part because some questions are just inherently unanswerable.尽管这家人工智能公司——最初是一家非营利组织，如今估值高达 5000 亿美元——完成了期待已久的重组，但其核心产品的一个棘手问题仍然悬而未决：幻觉。大型语言模型（LLM），例如支撑 OpenAI 热门平台 ChatGPT 的那些模型，很容易自信地发表与事实不符的言论。这些错误通常被归咎于糟糕的输入数据，但在上个月发表的一篇预印本论文中，OpenAI 和佐治亚理工学院的一个团队证明，即使拥有完美的训练数据，LLM 也永远不可能无所不知——部分原因是有些问题本身就无法回答。 However, that doesn’t mean hallucinations are inevitable. An AI could just admit three magic words: I don’t know. So why don’t they?然而，这并不意味着幻觉是不可避免的。人工智能完全可以坦白三个字：“我不知道 ”。 那么，它们为什么不这么做呢？ The root problem, the researchers say, may lie in how LLMs are trained. They learn to bluff because their performance is ranked using standardized benchmarks that reward confident guesses and penalize honest uncertainty. In response, the team calls for a rehaul of benchmarking so accuracy and self-awareness count as much as confidence.研究人员表示，问题的根源可能在于逻辑推理模型（LLM）的训练方式。由于其表现是根据标准化的基准进行排名，而这些基准会奖励自信的猜测，惩罚诚实的犹豫，因此 LLM 会学会虚张声势。为此，研究团队呼吁改革基准体系 ，使准确性和自我意识与自信程度同等重要 。 Although some experts find the preprint technically compelling, reactions to its suggested remedy vary. Some even question how far OpenAI will go in taking its own medicine to train its models to prioritize truthfulness over engagement. The awkward reality may be that if ChatGPT admitted “I don’t know” too often, then users would simply seek answers elsewhere. That could be a serious problem for a company that is still trying to grow its user base and achieve profitability. “Fixing hallucinations would kill the product,” says Wei Xing, an AI researcher at the University of Sheffield.尽管一些专家认为这篇预印本在技术上颇具说服力，但对于其提出的解决方案，各方反应不一。甚至有人质疑 OpenAI 究竟会在多大程度上以身作则，训练其模型优先考虑真实性而非互动性。一个棘手的现实可能是，如果 ChatGPT 频繁地承认“我不知道”，用户就会转而从其他地方寻找答案。对于一家仍在努力扩大用户群并实现盈利的公司来说，这可能是一个严重的问题。“修复幻觉问题会毁了这款产品，”谢菲尔德大学的人工智能研究员魏星（音译）说道。 Hallucinations begin during what’s known as pretraining, when the model first ingests massive amounts of text and begins to learn how to statistically predict the next word in a sequence. As Arizona State University computer scientist Subbarao Kambhampati puts it, an LLM fresh from pretraining amounts to an autocomplete tool “on steroids.” This early-stage model can handle straightforward patterns such as grammar or spelling with ease, but it can still go astray when asked to answer tricky factual questions.幻觉现象始于所谓的预训练阶段，此时模型首次接收大量文本并开始学习如何通过统计方法预测序列中的下一个词。正如亚利桑那州立大学计算机科学家苏巴拉奥·坎巴姆帕蒂所说，刚刚完成预训练的语言学习模型（LLM）就像一个“打了兴奋剂”的自动补全工具。这个早期模型可以轻松处理语法或拼写等简单的模式，但在回答棘手的、事实性的问题时仍然可能出错。 To explain why pretraining alone can’t keep an LLM on the straight and narrow, Georgia Institute of Technology theoretical computer scientist Santosh Vempala and his colleagues reimagined the problem: When prompted with a sentence, how accurate is the LLM when it’s asked to generate an assessment of whether the sentence is fact or fiction? If a model can’t reliably distinguish valid sentences from invalid ones, it will inevitably generate invalid sequences itself.为了解释为什么仅靠预训练无法保证语言学习模型（LLM）始终保持正确运行，佐治亚理工学院理论计算机科学家桑托什·文帕拉（Santosh Vempala）及其同事重新构想了这个问题：当被要求向 LLM 提供一个句子时，它判断该句子是事实还是虚构的准确率如何？如果模型无法可靠地区分有效句子和无效句子，那么它自身必然会生成无效的序列。 The math turned up a surprisingly simple association. A model’s overall error rate when producing text must be at least twice as high as its error rate when classifying sentences as true or false. Put simply, models will always err because some questions are inherently hard or simply don’t have a generalizable pattern. “If you go to a classroom with 50 students and you know the birthdays of 49 of them, that still gives you no help with the 50th,” Vempala says.数学计算揭示了一个出人意料的简单关联。模型在生成文本时的总体错误率必须至少是其在判断句子真假时的错误率的两倍。简而言之，模型总是会出错，因为有些问题本身就很难，或者根本不存在可推广的模式。“如果你走进一个有 50 个学生的教室，你知道其中 49 个学生的生日，但这仍然无法帮助你找到第 50 个学生的生日，”Vempala 说道。 “The reality is that we won’t [ever] get to 100% accuracy,” adds co-author Adam Kalai, a research scientist at OpenAI. “But that doesn’t mean language models have to hallucinate.”“现实情况是，我们永远无法达到 100%的准确率，”合著者、OpenAI 的研究科学家亚当·卡莱补充道。“但这并不意味着语言模型就必须凭空产生幻觉。” That tendency is cemented during posttraining, a later stage when human feedback and other fine-tuning methods steer the pretrained model to be safer and more accurate. Its answers are judged by benchmarks, standardized tests that score how well models answer thousands of questions.这种趋势在训练后阶段得到巩固。训练后阶段是指在人工反馈和其他微调方法的辅助下，预训练模型变得更加安全、更加准确。模型的答案会通过基准测试进行评判，这些基准测试是标准化的，用于评估模型回答数千个问题的表现。 High benchmark scores translate into prestige and commercial success, so companies often tune their posttraining to maximize benchmark scores. However, nine out of the 10 most popular benchmarks the researchers analyzed grade a correct answer as a 1 and a blank or incorrect answer as a 0. Because the benchmark doesn’t penalize incorrect guesses more than nonanswers, a fake-it-till-you-make-it model almost always ends up looking better than a careful model that admits uncertainty.高基准测试分数能够转化为声望和商业成功，因此公司通常会调整其训练后策略以最大化基准测试分数。然而，研究人员分析的10个最常用基准测试中，有9个将正确答案评为1分，将空白或错误答案评为0分。由于这些基准测试对错误猜测的惩罚力度与未作答相同，因此，一种“假装成功直到真正成功”的模型几乎总是比一个承认不确定性的谨慎模型表现更好。 This long-standing tradition may also be why other proposed hallucination solutions haven’t stuck, Kalai hypothesizes. Of the hundreds of benchmarks available, only a few systematically test how often a model hallucinates facts. The researchers call for reworking all benchmarks to penalize a model for guessing incorrectly. That could embed a “school of hard knocks” intuition in the model, teaching it humility. “It’s really almost a trivial change by most standards,” Kalai says.卡莱推测，这种由来已久的传统或许也是其他提出的幻觉解决方案未能奏效的原因。在数百个现有的基准测试中，只有少数几个系统地测试了模型产生幻觉事实的频率。研究人员呼吁重新设计所有基准测试，对模型的错误猜测进行惩罚。这或许能让模型积累“实战经验”，培养其谦逊的品质。“从大多数标准来看，这几乎是一个微不足道的改变，”卡莱说道。 “I buy a lot of what they’re proposing,” says Princeton University computer scientist Carlos Jimenez, who created SWE-Bench, one of the 10 benchmarks analyzed in the preprint. However, he notes that changing how benchmarks are scored may be tricky, in part because of the sheer diversity of topics that LLMs are benchmarked against. “Every particular subject is going to have some uniqueness in how you’re going to evaluate uncertainty or confidence,” he says.“我赞同他们提出的很多观点，”普林斯顿大学计算机科学家卡洛斯·希门尼斯说道。他创建了 SWE-Bench，这是预印本中分析的 10 个基准测试之一。然而，他指出，改变基准测试的评分方式可能很棘手，部分原因是 LLM 基准测试所针对的主题极其多样化。“每个特定主题在评估不确定性或置信度方面都会有一些独特之处，”他说道。 Others worry that even well-intentioned fixes could backfire. Hao Peng, a computer scientist at the University of Illinois Urbana-Champaign, cautions that incentivizing models to say “I don’t know” could warp their behavior in unexpected ways, just as optimizing for current benchmarks fosters hallucinations. “I’m a bit pessimistic if there’s any set of data or metric that would naturally fix hallucination,” he says. “These models are just so good at gaming whatever we’re optimizing them for.”另一些人则担心，即使是出于好意的改进措施也可能适得其反。伊利诺伊大学厄巴纳-香槟分校的计算机科学家郝鹏警告说，激励模型说“我不知道”可能会以意想不到的方式扭曲它们的行为，就像针对当前基准进行优化会滋生幻觉一样。“如果存在任何数据集或指标能够自然地解决幻觉问题，我对此持悲观态度，”他说。“这些模型太擅长钻我们优化它们的空子了。” In the meantime, whether the “I don’t know” approach takes hold will depend on AI companies themselves. “Capital expenditures, energy costs, and computing costs are rising, but performance is suffering from diminishing returns,” says Delft University of Technology economist Servaas Storm, who also points out that only 5% of OpenAI’s users are willing to pay for a $20 monthly subscription. Under these conditions, no one wants to be the first to break the long-standing industry norm, as users may migrate to seemingly more confident competitors.与此同时，“我不知道”这种态度能否盛行，将取决于人工智能公司自身。代尔夫特理工大学经济学家塞尔瓦斯·斯托姆指出：“资本支出、能源成本和计算成本都在上涨，但性能提升却面临收益递减的困境。”他还指出，OpenAI 的用户中只有 5% 愿意支付每月 20 美元的订阅费。在这种情况下，没有人愿意率先打破长期以来的行业惯例，因为用户可能会转向那些看起来更有信心的竞争对手。 “If LLMs keep pleading the Fifth, they can’t be wrong,” Kambhampati says. “But they’ll also be useless.”“如果法学硕士们继续援引第五修正案，他们就不可能犯错，”坎巴姆帕蒂说。“但他们也将毫无用处。”Feature  特征A foundation of trust信任的基础 A 3-decade partnership between archaeologists and the Kuikuro people offers a model of collaboration—and documents the complexity of early Amazonian societies考古学家与库伊库罗人长达三十年的合作，为合作树立了典范，并记录了早期亚马逊社会的复杂性。 Commentary  评论Expert Voices  专家之声The role of organizations in fostering innovation组织在促进创新中的作用 Unbiased discovery of neuronal architectures无偏倚地发现神经元结构 Comparative whole-brain and single-cell analyses identify neurons orchestrating neurological functions比较全脑和单细胞分析，可以识别出协调神经功能的神经元Cell signaling meets gene transcription细胞信号传导与基因转录相遇 Receptor tyrosine kinases directly regulate RNA polymerase II in the nucleus受体酪氨酸激酶直接调控细胞核内的 RNA 聚合酶 II。Seipin-adipogenin controls lipid storage in fat cells脂联素-脂肪原蛋白控制脂肪细胞中的脂质储存 A protein complex promotes the expansion of lipid droplets during the formation of mature adipocytes一种蛋白质复合物促进成熟脂肪细胞形成过程中脂滴的扩张。 Shrinking interconnects beyond copper超越铜的互连技术 Quantum materials can speed up the information processing in a computer chip量子材料可以加快计算机芯片中的信息处理速度。Policy Forum  政策论坛The need for a global effort to attend to human neural organoid and assembloid research需要全球共同努力关注人类神经类器官和组装类器官的研究 A continuing international process is needed to monitor and advise this rapidly progressing field需要持续开展国际合作，以监测和指导这一快速发展的领域。Books et al.  书籍等Frankenstein and the problem of abandonment弗兰肯斯坦与遗弃问题 A new adaptation of the cautionary tale is an opportunity to reflect on scientific stewardship对这个警世故事的新改编，为我们反思科学管理提供了一个契机。 Platforms of power  权力平台 A legal scholar pushes for net neutrality and other actions to rein in tech monopolies一位法学学者力主网络中立原则及其他措施，以遏制科技垄断。 Letters  信件Protect Iraq’s Mesopotamian Marshes保护伊拉克的美索不达米亚沼泽地 Britain must step up on AI policy英国必须加强人工智能政策 FDA export restrictions threaten collaborationFDA 的出口限制威胁着合作 Unlocking the potential of brassinosteroids: A path to precision plant engineering释放油菜素甾醇的潜力：通往精准植物工程之路 Essays  论文Understanding nature and nurture: Statistical and AI innovations uncover how genes and environment shape human health了解先天与后天：统计学和人工智能创新揭示基因和环境如何塑造人类健康 Statistical and AI innovations uncover how genes and environment shape human health统计学和人工智能创新揭示了基因和环境如何塑造人类健康The normalization of (almost) everything: Our minds can get used to anything, and even crises start feeling normal几乎所有事物都趋于正常化：我们的思维可以适应任何事物，甚至危机也开始变得习以为常。 Our minds can get used to anything, and even crises start feeling normal我们的大脑可以适应任何事物，甚至危机也会变得习以为常。Research  研究Research Highlights  研究亮点In Science Journals  在科学期刊上Reef Biodiversity  珊瑚礁生物多样性Reef regions as biodiversity hotspots珊瑚礁地区作为生物多样性热点地区 Rachel Wood  瑞秋·伍德 Analysis of the fossil record indicates that reefs, such as the site pictured here, enrich animal biodiversity in their surrounding regions.化石记录分析表明，珊瑚礁（例如图中所示的地点）丰富了周围地区的动物生物多样性。 PHOTO: RICHCAREY/ISTOCK PHOTO图片：RICHCAREY/ISTOCK PHOTO Reefs house considerable marine biodiversity and have done so for most of their long geological his tory. However, we know little about how the broader geographical regions that house reefs might also contribute to diversity over evolutionary timescales. Close et al. quantified the distribution of regional diversity through time, showing that regions with reefs have consistently shown far higher diversity compared with non-reef-supporting regions over evolutionary timescales. This observation suggests that reefs themselves enrich the diversity of their surrounding environments. Regions that support reefs have therefore been key hotspots of marine diversity throughout the evolutionary history of animals.珊瑚礁孕育着丰富的海洋生物多样性，在其漫长的地质历史中一直如此。然而，我们对珊瑚礁所在的更广阔的地理区域如何在进化时间尺度上促进生物多样性知之甚少。Close 等人量化了区域生物多样性随时间变化的分布，结果表明，在进化时间尺度上，拥有珊瑚礁的区域的生物多样性始终远高于没有珊瑚礁的区域。这一观察结果表明，珊瑚礁本身能够丰富其周围环境的生物多样性。因此，在动物的进化史上，拥有珊瑚礁的区域一直是海洋生物多样性的关键热点地区。 Sci. Adv. (2025) 10.1126/sciadv.adv9793科学进展 (2025) 10.1126/sciadv.adv9793Ultrafast Dynamics  超快动力学Clocking inverse CISS  时钟反向 CISS Jake S. Yeston  杰克·S·耶斯顿 Chirality induced spin selectivity (CISS) describes the effect of a chiral medium on the spin of electrons traversing it. Despite over two decades of detailed empirical observations, the mechanistic underpinnings of CISS remain somewhat mysterious. Dong et al. now report measurements of the ultrafast dynamics of an inverse CISS effect, in which terahertz emission elucidates spin-to-charge conversion in a chiral methylbenzylammonium lead iodide perovskite. The results are more consistent with a spin-polarization mechanism than with a spin-filtering mechanism.手性诱导自旋选择性（CISS）描述了手性介质对穿过其中的电子自旋的影响。尽管经过二十多年的详细实验观察，CISS 的机制基础仍然有些神秘。Dong 等人现在报道了反向 CISS 效应的超快动力学测量结果，其中太赫兹发射阐明了手性甲基苄基铵碘化铅钙钛矿中的自旋-电荷转换。结果更符合自旋极化机制，而非自旋过滤机制。 Science p. 595, 10.1126/science.ady4885科学 ，第 595 页， 10.1126/science.ady4885Climate Impacts  气候影响As the world warms随着全球变暖 Jesse Smith  杰西·史密斯 As global surface air temperatures continue to rise, so do the temperatures of individual components of our environment. Fleischmann et al. report an extreme example of that pattern: a simultaneous severe drought and heat wave in the Amazon in 2023. This combination led to high mortality of fishes and river dolphins, with the temperature of multiple lakes in the region studied reaching record highs and one entire lake reaching 41°C. Ongoing climate change likely will cause more instances like this where temperatures approach or exceed thermal tolerances for aquatic life.随着全球地表气温持续上升，我们环境中各个组成部分的温度也在不断升高。Fleischmann 等人报告了一个极端案例：2023 年亚马逊地区同时遭遇严重干旱和热浪。这种极端天气导致鱼类和河豚大量死亡，研究区域内多个湖泊的温度达到历史新高，其中一个湖泊的温度甚至高达 41 摄氏度。持续的气候变化很可能导致更多类似情况发生，届时水体温度将接近或超过水生生物的耐热极限。 Science p. 606, 10.1126/science.adr4029科学杂志第 606 页， 10.1126/science.adr4029Nonlinear Photonics  非线性光子学Tuning into nonlinear photonics调谐到非线性光子学 Ian S. Osborne  伊恩·S·奥斯本 Integrated nonlinear photonic technologies struggle in terms of scalability. The strict requirements of frequency and phase matching can be corrupted by the tiniest fabrication defects, leading to rapid performance deterioration nonuniformity across a wafer. Mehrabad et al. demonstrate a platform based on coupled silicon nitride ring resonator arrays that relax the strict phase-matching conditions and allow for broadband operation, thus easing the requirement for device fabrication. Being robust against fabrication errors, the approach should allow the development of integrated nonlinear photonic technologies at scale.集成非线性光子技术在可扩展性方面面临挑战。频率和相位匹配的严格要求很容易被微小的制造缺陷破坏，导致晶圆上的性能快速下降和不均匀性。Mehrabad 等人展示了一种基于耦合氮化硅环形谐振器阵列的平台，该平台放宽了严格的相位匹配条件，并允许宽带工作，从而降低了器件制造的要求。由于该方法对制造误差具有鲁棒性，因此有望实现集成非线性光子技术的规模化发展。 Science p. 612, 10.1126/science.adu6368科学 ，第 612 页， 10.1126/science.adu6368Quantum Simulation  量子模拟Open and critical  开放且批判 Jelena Stajic  耶莱娜·斯塔伊奇 Quantum criticality is characterized by universal power-law decays of correlations in real space. Fang et al. observed these decays using a programmable Rydberg simulator consisting of cesium atoms arranged in ring and square lattice geometries. The researchers extracted the characteristic scaling dimensions from the exponents of the power-law decays. By tuning the degree of openness of their system, they were able to study the impact of decoherence on the nature of quantum criticality.量子临界性的特征在于实空间中关联的普适幂律衰减。Fang 等人利用由铯原子排列成环状和正方形晶格几何结构的可编程里德堡模拟器观测到了这些衰减。研究人员从幂律衰减的指数中提取了特征标度维数。通过调节系统的开放程度，他们得以研究退相干对量子临界性本质的影响。 Science p. 601, 10.1126/science.adq0278科学杂志第 601 页， 10.1126/science.adq0278Volcanoes  火山A shear way to get bubbles剪切法获得气泡 Angela Hessler  安吉拉·赫斯勒 Volcanoes are ruled by bubbles, which give magma the buoyancy and compressibility needed to erupt. In magma, the nucleation of bubbles is difficult to observe but is thought to be triggered by decompression and crystallization. Roche et al. wondered if a more kinetic process might be at play: viscous shear. In a series of experiments with a carbon dioxide–supersaturated magma–liquid analog, the authors applied rotation to the liquid and observed bubble nucleation and growth through a transparent shaft. Simulations and dimensional analysis indicated that shear-induced bubble nucleation in volcano conduits is likely to factor into decompression estimates and eruptive style.火山活动受气泡支配，气泡赋予岩浆喷发所需的浮力和可压缩性。在岩浆中，气泡的成核过程难以观察，但人们认为它是由减压和结晶触发的。Roche 等人提出，可能存在一种更具动力学特性的过程：粘性剪切。在一系列使用二氧化碳过饱和岩浆-液体类似物的实验中，作者对液体施加旋转力，并通过透明通道观察气泡的成核和生长。模拟和量纲分析表明，火山通道中剪切诱导的气泡成核很可能影响减压程度的估算和喷发方式。 Science p. 633, 10.1126/science.adw8543科学杂志第 633 页， 10.1126/science.adw8543Autoimmunity  自身免疫Kidney chaos with Y-RNAY RNA 引起的肾脏紊乱 Christiana N. Fogg  克里斯蒂安娜·N·福格 The cytosolic receptor retinoic acid–inducible gene I (RIG-I) is a critical sensor of viral RNA and does not typically respond to self-RNA. But RIG-I gain-of-function mutations have been described in individuals with autoimmune disorders. Satoh et al. observed that a mouse model expressing a RIG-I patient variant developed spontaneous lupus-like nephritis, which was linked to monocyte chemotaxis and interstitial inflammation that resulted in renal dysfunction. Unlike classic lupus nephritis, immunoglobulin G–nucleic acid complexes did not drive this pathology. However, the variant of RIG-I could bind to short noncoding Y-RNA from kidney-derived cells, which induced RIG-I activation and downstream interferon-I responses. Together, these findings describe an unexpected role for Y-RNA in engaging a pathologic RIG-I variant.胞质受体视黄酸诱导基因 I (RIG-I) 是病毒 RNA 的关键传感器，通常对自身 RNA 无反应。但 RIG-I 功能获得性突变已在自身免疫性疾病患者中被发现。Satoh 等人观察到，表达 RIG-I 患者变异体的鼠模型会自发出现狼疮样肾炎，这与单核细胞趋化性和间质炎症有关，最终导致肾功能障碍。与经典狼疮性肾炎不同，免疫球蛋白 G-核酸复合物并非该病理的驱动因素。然而，该 RIG-I 变异体能够与来自肾脏细胞的短链非编码 Y-RNA 结合，从而诱导 RIG-I 激活和下游干扰素-I 反应。综上所述，这些发现揭示了 Y-RNA 在激活致病性 RIG-I 变异体中发挥着意想不到的作用。 Sci. Immunol. (2025) 10.1126/scitranslmed.adx1135科学免疫学 (2025) 10.1126/scitranslmed.adx1135Hydroecology  水文生态学Differing metabolisms  不同的代谢方式 Jesse Smith  杰西·史密斯 River organisms are the most important influence on the transport of carbon and other nutrients from land to sea. These ecosystems have been considered predominantly net heterotrophic, but Maavara et al. reveal that the rivers of the continental US also display a broad range from extreme heterotrophy to autotrophy. Increases in riverine gross primary productivity are particularly sensitive to drought conditions, and more than 70% of river metabolism occurs in the western US.河流生物是陆地向海洋输送碳和其他营养物质的最重要影响因素。这些生态系统一直被认为主要为净异养型，但 Maavara 等人发现，美国大陆的河流也呈现出从极端异养到自养的广泛分布。河流总初级生产力的增加对干旱条件尤为敏感，超过 70%的河流代谢发生在美国西部。 Science p. 622, 10.1126/science.adu9843科学 ，第 622 页， 10.1126/science.adu9843Cancer  癌症Target acquired  目标已收购 Dorothy Hallberg  多萝西·霍尔伯格 Patients with estrogen receptor–positive (ER+) luminal breast cancer benefit from targeted ER therapy, but many patients often have de novo or acquired resistance and require additional treatment. Singh et al. explored the use of immunotherapy in mouse models and patients with ER+ breast cancer to overcome resistance. They identified a population of tumor-associated macrophages recruited by Delta-like ligand 1 on tumor cells that promoted immune suppression. Combined targeting of this ligand and programmed death ligand 1 overcame tamoxifen resistance in preclinical mouse models and patient-derived explants. These results suggest a promising new avenue of treatment that requires further exploration.雌激素受体阳性（ER + ）管腔型乳腺癌患者可从靶向 ER 治疗中获益，但许多患者常出现原发性或获得性耐药，需要接受额外治疗。Singh 等人探索了在小鼠模型和 ER + 乳腺癌患者中使用免疫疗法克服耐药性的方法。他们发现肿瘤细胞表面存在一群由 Delta 样配体 1 募集的肿瘤相关巨噬细胞，这些巨噬细胞能够促进免疫抑制。在临床前小鼠模型和患者来源的组织块中，联合靶向该配体和程序性死亡配体 1（PD-L1）可克服他莫昔芬耐药性。这些结果提示了一种有前景的新治疗途径，值得进一步研究。 Sci. Transl. Med. (2025) 10.1126/scitranslmed.adr6207科学转化医学 (2025) 10.1126/scitranslmed.adr6207Plant Science  植物科学Brassinosteroids in plant engineering植物工程中的油菜素甾醇 Madeleine Seale  玛德琳·西尔 Brassinosteroids are plant hormones with multiple roles in development and stress responses. They are perceived by plasma membrane receptors and act locally within cells through a well-established signaling pathway. Vukašinović et al. reviewed how advances in single-cell analysis and developments in gene editing are paving the way for precision engineering of crop plants. The authors propose that tissue-specific manipulation of brassinosteroid action may help to improve crop growth and avoid the unwanted systemic effects of brassinosteroid misregulation.油菜素甾醇是一类植物激素，在植物发育和胁迫反应中发挥多种作用。它们通过质膜受体被感知，并通过一套成熟的信号通路在细胞内局部发挥作用。Vukašinović 等人综述了单细胞分析和基因编辑技术的进步如何为作物精准工程化铺平道路。作者提出，组织特异性地调控油菜素甾醇的作用可能有助于改善作物生长，并避免油菜素甾醇失调带来的不良系统性影响。 Science p. 583, 10.1126/science.adu9798科学 ，第 583 页， 10.1126/science.adu9798Molecular Biology  分子生物学Chromatin fatigue after DNA damage repairDNA 损伤修复后的染色质疲劳 Di Jiang  蒋 Cells organize their DNA in a three-dimensional structure that helps control which genes are turned on or off. Bantele et al. investigated whether this structure fully recovers after DNA damage is repaired. The researchers introduced precise DNA breaks and tracked changes in genome organization and gene activity. They found that even after the DNA was repaired, the affected regions remained misfolded and showed reduced gene expression, and these changes were passed on to daughter cells. DNA damage thus leaves lasting marks on genome function, a phenomenon called “chromatin fatigue,” which has important implications for aging, disease, and gene-editing technologies such as CRISPR.细胞将 DNA 组织成三维结构，以控制哪些基因被开启或关闭。Bantele 等人研究了 DNA 损伤修复后这种结构是否能完全恢复。研究人员人为制造了精确的 DNA 断裂，并追踪了基因组结构和基因活性的变化。他们发现，即使 DNA 修复后，受损区域仍然处于错误折叠状态，基因表达降低，并且这些变化会遗传给子细胞。因此，DNA 损伤会在基因组功能上留下持久的痕迹，这种现象被称为“染色质疲劳”，它对衰老、疾病以及 CRISPR 等基因编辑技术具有重要意义。 Science p. 589, 10.1126/science.adk6662科学杂志第 589 页， 10.1126/science.adk6662Cardiology  心脏病学Fibroblasts remodeling the heart成纤维细胞重塑心脏 Yevgeniya Nusinovich  叶夫根尼娅·努西诺维奇 Dilated cardiomyopathy is characterized by myocardial thinning, ventricular enlargement, and diminished cardiac function. It is a major cause of heart failure and is caused by a variety of mutations or acquired damage to the heart. Despite its prevalence, the pathogenesis of this disorder is not fully understood and treatments are limited. Given that fibrosis is a common feature of dilated cardiomyopathy and fibroblasts contribute to cardiac remodeling, Bretherton et al. examined the effects of a disease-causing mutation on fibroblasts. Although the mutation was only present in cardiomyocytes, it altered the functioning of surrounding fibroblasts, promoting their proliferation and extracellular matrix stiffening and thereby worsening cardiac function. Conversely, targeting mechanotransduction in these fibroblasts prevented the deleterious changes in cardiac structure and function.扩张型心肌病以心肌变薄、心室扩大和心功能下降为特征。它是心力衰竭的主要原因之一，由多种基因突变或心脏后天损伤引起。尽管该病发病率很高，但其发病机制尚未完全阐明，治疗方法也十分有限。鉴于纤维化是扩张型心肌病的常见特征，且成纤维细胞参与心脏重塑，Bretherton 等人研究了一种致病突变对成纤维细胞的影响。虽然该突变仅存在于心肌细胞中，但它改变了周围成纤维细胞的功能，促进了成纤维细胞的增殖和细胞外基质硬化，从而加重了心脏功能障碍。相反，靶向这些成纤维细胞的机械转导可以阻止心脏结构和功能的有害改变。 Science p. 590, 10.1126/science.adv9157科学杂志第 590 页， 10.1126/science.adv9157Immunology  免疫学Redesigning antibody therapeutics重新设计抗体疗法 Sarah H. Ross  莎拉·H·罗斯 Autoimmune diseases can be treated by intravenous immunoglobulin (IVIG), a therapeutic that requires substantial quantities of antibodies to be collected from large numbers of healthy human donors. Based on one proposed mechanism of action for IVIG, Jones et al. produced an antibody tail fragment known as the Fc region and modified it so that it inhibited pathology in mouse modals of autoimmunity with a lower dose than IVIG. This engineered Fc protein was modified by sialylation and contained mutations that increased its interaction with a type I receptor known as FcγRIIB. The interaction between FcγRIIB and another receptor, DC-SIGN, promoted the binding of isolated Fc fragments and antibodies to cells.自身免疫性疾病可通过静脉注射免疫球蛋白（IVIG）治疗，但这种疗法需要从大量健康人供体中采集大量的抗体。基于 IVIG 的一种作用机制，Jones 等人制备了一种称为 Fc 区的抗体尾片段，并对其进行改造，使其能够以低于 IVIG 的剂量抑制小鼠自身免疫模型中的病理变化。这种经过改造的 Fc 蛋白经唾液酸化修饰，并包含增强其与 I 型受体 FcγRIIB 相互作用的突变。FcγRIIB 与另一种受体 DC-SIGN 的相互作用促进了分离的 Fc 片段和抗体与细胞的结合。 Science p. 591, 10.1126/science.adv2927科学杂志第 591 页， 10.1126/science.adv2927Synthetic Biology  合成生物学De novo mRNA design enhances translation从头 mRNA 设计增强翻译 Di Jiang  蒋 Generative models have advanced small-molecule and protein design, but their application to messenger RNA (mRNA) remains challenging because of the complexity of translational regulation and sequence-structure-function relationships. Zhang et al. present GEMORNA, a generative AI framework that learns intrinsic biological patterns from natural mRNA sequences and enables de novo sequence design with strong contextual coherence and diversity through autoregressive decoders. GEMORNA has demonstrated potential as a generalized mRNA design platform through case studies showing enhanced and prolonged protein expression in cell-based assays and animal models. These findings are relevant to current mRNA therapeutic applications, including mRNA vaccines, protein replacement therapies, and in vivo chimeric antigen receptor T cell treatments.生成模型已推动小分子和蛋白质设计的发展，但由于翻译调控和序列-结构-功能关系的复杂性，将其应用于信使 RNA (mRNA) 仍然面临挑战。Zhang 等人提出了 GEMORNA，这是一个生成式人工智能框架，它能够从天然 mRNA 序列中学习内在的生物学模式，并通过自回归解码器实现具有强上下文一致性和多样性的从头序列设计。案例研究表明，GEMORNA 作为通用 mRNA 设计平台具有巨大潜力，在基于细胞的实验和动物模型中均能增强和延长蛋白质表达。这些发现与当前的 mRNA 治疗应用密切相关，包括 mRNA 疫苗、蛋白质替代疗法和体内嵌合抗原受体 T 细胞疗法。 Science p. 592, 10.1126/science.adr8470科学杂志第 592 页， 10.1126/science.adr8470Cell Biology  细胞生物学Adipogenin, seipin, and lipid droplets脂肪生成素、seipin 和脂滴 Stella M. Hurtley  斯特拉·M·赫特利 Fat storage in the body relies on specialized structures called lipid droplets (LDs). Li et al. identified the microprotein adipogenin as a regulator of adipocyte LD size (see the Perspective by Wu and Yang). Adipogenin interacts with the membrane protein seipin and stabilizes the assembly of seipin dodecamers by bridging adjacent subunits. Functionally, seipin-adipogenin complexes promote the formation of fewer but larger LDs. In mice, adipocyte-specific adipogenin overexpression results in increased fat mass and larger LDs, whereas adipogenin deletion reduces fat accumulation and LD size, particularly in brown adipose tissue. Thus, adipogenin represents a modulator of adipocyte lipid storage that acts through a structural and functional partnership with seipin.体内脂肪的储存依赖于一种称为脂滴（LDs）的特殊结构。Li 等人发现微蛋白脂肪生成素（adipogenin）是脂肪细胞脂滴大小的调节因子（参见 Wu 和 Yang 的观点文章）。脂肪生成素与膜蛋白 seipin 相互作用，并通过连接相邻亚基来稳定 seipin 十二聚体的组装。在功能上，seipin-脂肪生成素复合物促进形成数量较少但体积更大的脂滴。在小鼠中，脂肪细胞特异性过表达脂肪生成素会导致脂肪量增加和脂滴增大，而脂肪生成素缺失则会减少脂肪积累和脂滴大小，尤其是在棕色脂肪组织中。因此，脂肪生成素通过与 seipin 的结构和功能相互作用来调节脂肪细胞的脂质储存。 Science p. 593, 10.1126/science.adr9755; see also p. 570, 10.1126/science.aec4109《科学》杂志第 593 页， 10.1126/science.adr9755 ；另见第 570 页， 10.1126/science.aec4109Molecular Biology  分子生物学Cell signaling kinases target Pol II细胞信号激酶靶向 Pol II Di Jiang  蒋 RNA polymerase II (Pol II) function is regulated by phosphorylation at specific residues within its intrinsically disordered C-terminal domain (CTD). Traditionally, only a few closely related kinases were known to target two positions within the heptapeptide repeats of the CTD. Dabas et al. now report that more than 100 additional cell signaling kinases spanning diverse families can selectively phosphorylate previously uncharacterized “orphan” residues of the CTD (see the Perspective by Young). This expanded atlas of the CTD kinome provides a foundation for investigating how signaling kinases directly regulate polymerase function across different physiological and pathological contexts.RNA 聚合酶 II (Pol II) 的功能受其固有无序 C 端结构域 (CTD) 内特定残基磷酸化的调控。传统上，人们只知道少数密切相关的激酶靶向 CTD 七肽重复序列中的两个位点。Dabas 等人现在报道，超过 100 种来自不同家族的细胞信号激酶能够选择性地磷酸化 CTD 中先前未被鉴定的“孤儿”残基（参见 Young 的观点）。这一扩展的 CTD 激酶组图谱为研究信号激酶如何在不同的生理和病理条件下直接调控聚合酶的功能奠定了基础。 Science p. 594, 10.1126/science.ads7152; see also p. 568, 10.1126/science.aec1434《科学》杂志第 594 页， 10.1126/science.ads7152 ；另见第 568 页， 10.1126/science.aec1434Solar Cells  太阳能电池Evenly distributing chloride ions氯离子均匀分布 Phil Szuromi  菲尔·斯祖罗米 The uneven distribution of ions from the additives used to improve perovskite films is a major problem for solar cells made of these materials. Xiong et al. found that methylammonium chloride, which is added to lower the nucleation barrier for forming the desired intermediate state during the growth of formamidinium lead iodide, creates a through-film inhomogeneity of chloride ions that degrades performance. The researchers found that adding potassium binoxalate during thermal processing homogenized the chloride distribution by forming potassium chloride and, in turn, improved device performance.用于改善钙钛矿薄膜的添加剂导致离子分布不均，这是由这些材料制成的太阳能电池面临的主要问题。Xiong 等人发现，在甲脒碘化铅生长过程中，为了降低形成所需中间态的成核势垒而添加的氯化甲铵，会造成氯离子在薄膜内的分布不均匀，从而降低器件性能。研究人员发现，在热处理过程中添加草酸钾可以通过生成氯化钾来使氯离子分布均匀，进而提高器件性能。 Science p. 638, 10.1126/science.adw8780科学杂志第 638 页， 10.1126/science.adw8780Metallurgy  冶金Annealing to make strong faults退火形成强缺陷 Marc S. Lavine  马克·S·拉文 Reducing the grain size in metals increases their strength, but the highest strength achieved in nanograined and nanotwinned metals is well below the theoretical strength because of the instability of grain and twin boundaries. Li et al. took a different approach to strengthening nickel alloys through the manipulation of nanoscale interfaces exhibiting negative excess energy. Using density functional theory calculations, they showed that the coherent interfaces between ABCABC stacking and ABAB stacking layers are highly stable. Supersaturated nickel-molybdenum solution was deposited by pulsed electrodeposition. The as-deposited films have an amorphous phase, and crystallization using various annealing strategies produced high-density stacking faults and twin boundaries with spacing below 10 nanometers. These faults are not the result of plastic deformation or the addition of specific impurities but instead form during annealing from an amorphous phase.减小金属的晶粒尺寸可以提高其强度，但由于晶粒和孪晶界的不稳定性，纳米晶粒和纳米孪晶金属所能达到的最高强度远低于理论强度。Li 等人采用了一种不同的方法来强化镍合金，即通过调控具有负过剩能量的纳米级界面。他们利用密度泛函理论计算表明，ABCABC 堆垛层和 ABAB 堆垛层之间的共格界面具有很高的稳定性。他们采用脉冲电沉积法沉积了过饱和的镍钼溶液。沉积态薄膜呈非晶态，通过不同的退火策略进行结晶后，产生了间距小于 10 纳米的高密度堆垛层错和孪晶界。这些缺陷并非塑性变形或特定杂质添加的结果，而是在非晶态退火过程中形成的。 Science p. 617, 10.1126/science.aea4299科学杂志第 617 页， 10.1126/science.aea4299Sea Ice  海冰A frozen sea  冰封的海洋 Jesse Smith  杰西·史密斯 Sea ice coverage in the Arctic has been declining rapidly over the past several decades because of the influence of anthropogenic warming, which is occurring faster in the Arctic region than in any other on the globe. Pavia et al. used helium-3 and thorium-230 isotopes to reconstruct the history of sea ice coverage of the central Arctic over the past 30,000 years. They concluded that this region was perennially covered during the last glaciation, had decreased coverage during the deglaciation, and became seasonally covered in the warmer-than-present early Holocene. An observed correlation with biological nutrient consumption has implications for the productivity of the region as climate warming progresses.过去几十年，受人为温室效应的影响，北极海冰覆盖面积迅速减少，而北极地区的变暖速度比全球其他任何地区都快。Pavia 等人利用氦-3 和钍-230 同位素重建了过去 3 万年来北极中部海冰覆盖的历史。他们的研究结果表明，该地区在末次冰期常年被海冰覆盖，在冰消期海冰覆盖面积减少，而在比现在更温暖的全新世早期则呈现季节性海冰覆盖。观测到的海冰覆盖与生物营养消耗之间的相关性，预示着随着气候变暖的加剧，该地区的生产力将受到影响。 Science p. 628, 10.1126/science.adv5767科学杂志第 628 页， 10.1126/science.adv5767Cancer  癌症PKCα signal gain after loss of functionPKCα信号在功能丧失后增强 Leslie Ferrarelli  莱斯利·法拉雷利 Inactivating mutations in the kinase PKCα are associated with various cancers. Calleja et al. found that the D463H mutation that causes the brain cancer chordoid glioma inactivates PKCα kinase activity but induces a gain-of-signal output through protein-protein interactions. D463H PKCα bound to ATP but lacked the ability to hydrolyze it, resulting in sustained interactions with effector proteins, an altered interactome, and enhanced gene expression programs. The mutation caused early-onset bone cancer in mice, demonstrating its dominant oncogenicity. These findings alter our understanding of kinase function and may inform clinical strategies.激酶 PKCα的失活突变与多种癌症相关。Calleja 等人发现，导致脑癌脊索样胶质瘤的 D463H 突变会使 PKCα激酶活性失活，但会通过蛋白质-蛋白质相互作用诱导信号增强。D463H PKCα能够结合 ATP，但缺乏水解 ATP 的能力，从而导致其与效应蛋白持续相互作用，改变相互作用组，并增强基因表达程序。该突变导致小鼠早发性骨癌，表明其具有显著的致癌性。这些发现改变了我们对激酶功能的理解，并可能为临床策略提供指导。 Sci. Signal. (2025) 10.1126/scisignal.adr0235科学信号 (2025) 10.1126/scisignal.adr0235Archaeology  考古学An early Maya cosmogram in Mexico墨西哥早期玛雅宇宙图 Mark Aldenderfer  马克·阿尔登德弗 Ancient societies with hierarchical social formations commonly built monumental architecture for both religious and political purposes. By contrast, nonhierarchical societies are thought to have had limited capacity to create large-scale monuments. An exception is Aguada Fénix, a Maya site that dates between 3000 and 2700 years ago. Through excavation and lidar imaging, Inomata et al. determined that the Maya constructed a massive complex of canals, corridors, and nested cruciate forms along two principal axes that stretched from 9 to 7.5 kilometers in length. The site is believed to be a cosmogram, a representation of the structure of the Maya universe. The authors suggest that participation in its creation was a motivation for people to build it without coercion by societal elites.古代社会等级森严，通常会建造宏伟的建筑用于宗教和政治目的。相比之下，非等级制社会被认为建造大型纪念碑的能力有限。阿瓜达菲尼克斯遗址是个例外，这是一处距今 3000 至 2700 年的玛雅遗址。通过挖掘和激光雷达成像，伊诺玛塔等人确定，玛雅人沿着两条主轴建造了一个庞大的建筑群，其中包含运河、走廊和嵌套的十字形结构，长度从 9 公里到 7.5 公里不等。该遗址被认为是一个宇宙图，代表了玛雅宇宙的结构。作者认为，参与建造是人们在没有社会精英强制的情况下建造这座遗址的动力。 Sci. Adv. (2025) 10.1126/sciadv.aea2037 Highlights from the Science family of journals《科学》 系列期刊的亮点In Other Journals  其他期刊 Editors’ selections from the current scientific literature编辑从当前科学文献中精选Plant Science  植物科学Lignin is laid at the tip of the thorn木质素沉积在刺的顶端。 Madeleine Seale  玛德琳·西尔 Growing thorns such as those of the pictured bitter orange (Citrus trifoliata) require multiple genes to coordinate lignin deposition.像图中所示的苦橙（ Citrus trifoliata ）那样长出刺的植物需要多个基因来协调木质素的沉积。 PHOTO: ARTERRA PICTURE LIBRARY/ALAMY图片：ARTERRA PICTURE LIBRARY/ALAMY Tough cell walls strengthen parts of plants that must resist pressure, such as thorns and prickles. Ren et al. investigated how secondary cell walls are deposited in the sharp tips of Citrus thorns. Using a CRISPR-based mutant screen of 20 candidate genes, the authors identified a set of transcription factors, including MYB62, that regulate lignin deposition in thorn tips. Homologs of MYB62 are expressed in thorn tips of several unrelated thorn-producing species, indicating that there may be convergent co-option of the lignification pathway.坚韧的细胞壁能够增强植物中需要承受压力的部位，例如刺和棘刺。Ren 等人研究了柑橘刺尖中次生细胞壁的沉积方式。他们利用基于 CRISPR 技术的突变体筛选方法，筛选了 20 个候选基因，并鉴定出一组转录因子，其中包括 MYB62，这些转录因子调控着刺尖中木质素的沉积。MYB62 的同源基因在几种不相关的刺植物的刺尖中均有表达，这表明木质化途径可能存在趋同进化。 Proc. Natl. Acad. Sci. U.S.A. (2025) 10.1073/pnas.2510775122美国国家科学院院刊 (2025) 10.1073/pnas.2510775122Hydrogels  水凝胶Capture, storage, release捕获、存储、发布 Marc S. Lavine  马克·S·拉文 Cells excrete lipid-bound vesicles known as extracellular vesicles (EVs), the cargos of which can include lipids, nucleic acids, and proteins. EVs are thus potentially useful for biomedical diagnostics if they can be isolated in large enough quantities. Kim et al. cryo-photocrosslinked an aqueous solution of polyethylene glycol diacrylate (PEGDA) to create particles with a combined meso-macro porosity. Pore size limits the object that can enter the gels, and the PEG chains only capture EVs with specific surface charges. EVs were extracted from many fluids without preprocessing, including whole blood, plasma, urine, and saliva. The authors also showed that they could preserve the EVs in the hydrogels for on-demand use.细胞会分泌脂质包裹的囊泡，称为细胞外囊泡（EVs），其携带的物质包括脂质、核酸和蛋白质。因此，如果能够从中分离出足够数量的 EVs，它们在生物医学诊断方面具有潜在的应用价值。Kim 等人利用冷冻光交联技术，将聚乙二醇二丙烯酸酯（PEGDA）水溶液制备成具有介孔和大孔组合孔隙的颗粒。孔径限制了能够进入凝胶的物质种类，而 PEG 链则只捕获具有特定表面电荷的 EVs。无需预处理，即可从多种体液中提取 EVs，包括全血、血浆、尿液和唾液。作者还证明，他们可以将 EVs 保存在水凝胶中，以便随时使用。 Nat. Nanotechnol. (2025) 10.1038/s41565-025-02011-1Atmospheric Chemistry  大气化学Hot flashes  潮热 Jesse Smith  杰西·史密斯 Lightning produces abundant amounts of NO2 in the free troposphere.闪电会在自由对流层中产生大量的二氧化氮 。 PHOTO: ERIC JESSUP  照片：埃里克·杰瑟普 Free tropospheric nitrogen dioxide (FT NO2) helps drive global atmospheric chemistry, but its sources are uncertain. Dang et al. used satellite observations to show that lightning dominates FT NO2 production in nonwinter seasons over North America, and that commonly used model estimates of its production contain large errors. The authors were also are able to detect diurnal variations of FT NO2. This work should help to improve atmospheric models and the ability to use NO2 observations from space to quantify surface NOx emissions.对流层自由二氧化氮（FT NO₂ ）是全球大气化学过程的重要驱动因素，但其来源尚不明确。Dang 等人利用卫星观测数据表明，在北美非冬季，闪电是 FT NO₂ 的主要来源，而常用的模型估算值存在较大误差。此外，他们还探测到了 FT NO₂ 的日变化。这项工作有助于改进大气模型，并提高利用太空观测的 NO₂ 数据量化地表 NOₓ 排放的能力。 Proc. Natl. Acad. Sci. U.S.A. (2025) 10.1073/pnas.2510535122美国国家科学院院刊 (2025) 10.1073/pnas.2510535122Adaptation  适应Big beak, small beak大喙，小喙 Corinne Simonti  科琳·西蒙蒂 Longer beaks are thought to be adaptive in wetter seasons in the yellow warbler (Setophaga petechia), but it is difficult to tie this information to fitness measurements and to determine the underlying genetic basis. Rodriguez et al. collected DNA and measured beak depth and telomere length (a fitness stand-in) from more than 100 modern and historic yellow warblers and compared these with local climate variables. The authors identified variants associated with beak depth and telomere length and found that precipitation correlated with changes in their frequency. They also found that a phenotype-environment mismatch, such as longer beaks in drier seasons, was associated with shortened telomeres, potentially indicating stress and a source of selection on maladapted individuals.人们认为，在雨季，黄莺（ Setophaga petechia ）的喙较长是一种适应性特征，但很难将这一信息与适应性指标联系起来，也难以确定其潜在的遗传基础。Rodriguez 等人采集了 100 多只现代和历史黄莺的 DNA，并测量了它们的喙深和端粒长度（端粒长度可作为适应性的替代指标），并将这些数据与当地气候变量进行了比较。作者鉴定出了与喙深和端粒长度相关的变异，并发现降水量与这些变异频率的变化呈正相关。他们还发现，表型与环境不匹配的情况，例如在旱季喙较长，与端粒缩短有关，这可能表明个体面临压力，并成为选择压力的来源。 Proc. Natl. Acad. Sci. U.S.A. (2025) 10.1073/pnas.2518497122美国国家科学院院刊 (2025) 10.1073/pnas.2518497122Cell Biology  细胞生物学A little bit at a time一点一点地来 Stella M. Hurtley  斯特拉·M·赫特利 Potentially harmful protein aggregates can be removed by aggrephagy, a selective type of autophagy. Mauthe et al. found that the chaperone system works in concert with the proteasome in the lysosomal elimination of different types of cellular aggregates by aggrephagy, including disease-associated huntingtin aggregates. The HSP70-HSP110-DNAJB6 chaperone module and the proteasomal 19S regulatory particle together form a fragmentase that can pinch off small pieces from large aggregates that otherwise resist lysosomal degradation. Fragmentation is accompanied by condensation of the aggregates, which triggers clustering of selective autophagy receptors on their surface, local phagophore or autophagosome formation, and lysosomal delivery.潜在有害的蛋白质聚集体可通过聚集体自噬（一种选择性自噬）清除。Mauthe 等人发现，分子伴侣系统与蛋白酶体协同作用，通过聚集体自噬清除溶酶体中的各种细胞聚集体，包括与疾病相关的亨廷顿蛋白聚集体。HSP70-HSP110-DNAJB6分子伴侣模块和蛋白酶体 19S 调节颗粒共同形成一种片段酶，能够从原本难以被溶酶体降解的大型聚集体上切割下小片段。片段化伴随着聚集体的凝聚，进而触发其表面选择性自噬受体的聚集、局部吞噬泡或自噬体的形成，最终将聚集体递送至溶酶体。 Nat. Cell Biol. (2025) 10.1038/s41556-025-01747-1Metabolism  代谢Fathering starts with a run为人父始于跑步 Mattia Maroso  马蒂亚·马罗索 Recent data have shown that both maternal and paternal exercise can enhance physical performance and general health in offspring through epigenetic mechanisms. Yin et al. studied the phenomenon in mice, focusing on paternal exercise. Endurance exercise changed sperm microRNAs, resulting in increased endurance capacity and metabolic benefits in offspring through a microRNA-mediated increase in mitochondrial biogenesis. Future mouse fathers might have their own way to promote physical health in offspring through endurance exercise.近期数据显示，父母双方的运动均可通过表观遗传机制增强后代的体能和整体健康。Yin 等人以小鼠为研究对象，重点关注父亲的运动。耐力运动改变了精子中的 microRNA，通过 microRNA 介导的线粒体生物合成增加，提高了后代的耐力和代谢水平。未来的小鼠父亲或许也能通过耐力运动来促进后代的体能健康。 Cell Metab. (2025) 10.1016/j.cmet.2025.09.003Photoemission  照片展示Evanescent excitation of photoelectrons光电子的倏逝波激发 Phil Szuromi  菲尔·斯祖罗米 Light traveling parallel to the surface of a silicon nitride waveguide efficiently excites photoemission from a 5-nanometer thick overlayer of cesium antimonide. Evanescent light only excites photoelectrons that can readily escape, unlike normal incidence light, which excites photoelectrons trapped in the bulk. Ahsan et al. used photoemission electron microscopy to image optical modes in the waveguide on length scales from 100 nanometers to 1 millimeter. This method can also create transverse features in the emitted electron beams at scales below about 600 nanometers.平行于氮化硅波导表面传播的光能够有效地激发厚度为 5 纳米的锑化铯覆盖层的光电发射。与垂直入射光激发被困在体相中的光电子不同，倏逝波仅激发易于逸出的光电子。Ahsan 等人利用光发射电子显微镜对波导中 100 纳米至 1 毫米尺度的光学模式进行了成像。该方法还可以在发射的电子束中形成尺度小于约 600 纳米的横向特征。 Nano Lett. (2025) 10.1021/acs.nanolett.5c03185Research Articles  研究文章Repair of DNA double-strand breaks leaves heritable impairment to genome functionDNA 双链断裂的修复会给基因组功能留下可遗传的损伤。 Deep generative models design mRNA sequences with enhanced translational capacity and stability深度生成模型设计具有增强的翻译能力和稳定性的 mRNA 序列。 Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex脂肪生成素通过与十二聚体 seipin 复合物结合来促进脂滴的形成。 Direct targeting and regulation of RNA polymerase II by cell signaling kinases细胞信号激酶对 RNA 聚合酶 II 的直接靶向和调控 The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptorsIgG 的抗炎活性可通过 I 型和 II 型 Fc 受体的共同结合而增强。 Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy预防低收缩力诱导的成纤维细胞增殖可缓解扩张型心肌病 Ultrafast inverse chirality-induced spin selectivity observed by THz emission利用太赫兹发射观测到的超快反手性诱导自旋选择性 Probing critical phenomena in open quantum systems using atom arrays利用原子阵列探测开放量子系统中的关键现象 Extreme warming of Amazon waters in a changing climate气候变化导致亚马逊水域极端升温 Multi-timescale frequency-phase matching for high-yield nonlinear photonics用于高产率非线性光子学的多时间尺度频率相位匹配 Strengthening Ni alloys with nanoscale interfaces of negative excess energy利用负过剩能量的纳米级界面强化镍合金 River metabolism in the contiguous United States: A West of extremes美国本土河流代谢：极端情况的西部 Cosmic dust reveals dynamic shifts in central Arctic sea-ice coverage over the past 30,000 years宇宙尘埃揭示了过去3万年来北极中部海冰覆盖的动态变化 Shear-induced bubble nucleation in magmas岩浆中剪切诱导气泡成核 Homogenized chlorine distribution for >27% power conversion efficiency in perovskite solar cells钙钛矿太阳能电池中氯分布均匀，功率转换效率超过27% When ‘we’ turns wicked当“我们”变得邪恶 The rejection email from an elite journal was still fresh when my two co-authors and I jumped on a Zoom call to commiserate. When I suggested another outlet we could try next, I was shocked by their immediate and vehement opposition. That’s when everything unraveled. They already had a paper under review there. I’d known about their other project using the same data set. But their paper had morphed substantially since I’d last seen it. Now, it looked disturbingly similar to ours. I was livid. This was my idea from the start. I had invested nearly 3 years working on it. Learning they had poached it felt like a huge betrayal—and transformed my approach to collaboration.收到顶级期刊的拒稿邮件后，我和两位合作者立刻在 Zoom 上进行了一次视频通话，互相安慰。当我建议我们可以尝试投稿到其他期刊时，他们立刻强烈反对，这让我大吃一惊。事情就此败露。他们已经有一篇论文正在接受审稿。我知道他们之前也用同样的数据集做过一个项目。但是自从我上次看到他们的论文以来，内容已经发生了很大的变化。现在，它看起来和我们的论文惊人地相似。我怒不可遏。这完全是我的原创想法。我为此投入了近三年的时间。得知他们窃取了我的创意，我感到无比的背叛——这彻底改变了我对待合作的态度。 My academic career started auspiciously with two fast, singleauthored publications. But when I pivoted from economics to business and management, I got nothing but rejections for a couple long years. I was an outsider in the field of management studies, and I thought collaboration would help me out of this quagmire. Increasingly I worked with co-authors, seeking mentorship from senior ones and complementarities and energy from the junior ones. The result was multiple publications, conference invitations, and a growing network of collaborators. I thought I had mastered the game and that “we” was the answer—until that Zoom call.我的学术生涯开局不错，很快就发表了两篇独立署名的论文。但当我从经济学转向商业和管理学时，却在接下来的几年里屡屡碰壁，论文都被拒稿。我当时在管理学领域是个外行，觉得合作或许能帮我摆脱困境。于是我开始越来越多地与人合作，向资深学者寻求指导，也从年轻学者那里汲取互补和活力。最终，我发表了多篇论文，收到了会议邀请，合作者网络也日益壮大。我以为自己已经掌握了诀窍，“我们”就是答案——直到那次 Zoom 通话。 I reached out to several senior journal editors for guidance and solutions. Dishearteningly, all advised me to drop it; authorship disputes, they said, are messy affairs where nobody wins. I felt utterly powerless. My health deteriorated, especially my mental state. I couldn’t sleep, couldn’t work, couldn’t even enjoy time with my family.我联系了几位资深期刊编辑寻求指导和解决方案。令人沮丧的是，他们都建议我放弃；他们说，署名权纠纷是一件棘手的事情，最终谁也赢不了。我感到彻底的无力感。我的健康状况每况愈下，尤其是精神状态。我失眠、无法工作，甚至无法享受与家人相处的时光。SIGN UP FOR OUR CAREERS NEWSLETTER订阅我们的职业简报 Get great career content biweekly!每两周获取精彩的职业内容！   报名 Nevertheless, I followed my heart and decided to fight back. I wrote to the journal where my former co-authors’ paper was under review. The journal ultimately rejected their paper—but based on reviewer recommendations, not ethical grounds. I contacted ethics officers at my institution and one of theirs. Though initially sympathetic, their message was consistent: Drop it, it’s messy, no one wins. Professional organizations to which we all belonged shrugged off my inquiries on the grounds of sporadic membership. I reached out to mutual co-authors from other projects, but they wouldn’t get involved either.然而，我还是听从了自己的内心，决定反击。我给之前合作者论文正在审稿的期刊写了信。期刊最终拒稿了——但拒稿的理由是审稿人的建议，而非伦理方面。我联系了我们机构和对方机构的伦理官员。虽然他们起初表示同情，但他们的回复始终如一：放弃吧，这事儿太棘手了，谁也赢不了。我们共同所属的专业组织也以会员人数不固定为由，对我的询问不予理睬。我还联系了其他项目的共同合作者，但他们也不愿介入。 I finally decided to move on and focus on other research. For nearly 2 years I worked alone—until I finally considered reviving the original project, which had never been published. Again, I would have to collaborate with others to put together the underlying data set. This thought filled me with anxiety. But I also knew isolation was not sustainable, and my productivity would suffer.我最终决定放弃之前的项目，转而专注于其他研究。近两年时间里，我一直独自工作——直到我最终考虑重启那个从未发表过的原始项目。这意味着我又得与他人合作，才能收集到所需的基础数据集。想到这一点，我就焦虑不已。但我同时也明白，这种孤立状态无法长久，我的工作效率也会受到影响。 After much thought, I found someone who seemed like a good fit for the project. Before our first substantive conversation, I proposed something I’d never asked before: a formal collaboration agreement. We outlined roles, established authorship criteria based on concrete contributions, and agreed to document key decisions via email rather than casual chats. A couple of years later, we published the research together using a much larger data set and more sophisticated statistical analyses than before.经过深思熟虑，我找到了一个似乎很适合这个项目的人。在我们第一次正式交谈之前，我提出了一个我以前从未提过的要求：一份正式的合作协议。我们明确了各自的角色，根据具体贡献制定了署名标准，并同意通过电子邮件而非随意聊天来记录关键决策。几年后，我们共同发表了这项研究成果，这次我们使用了比以往更大的数据集和更复杂的统计分析方法。 Beyond vindication, the lessons I learned have reshaped my approach to collaboration. First, safeguard self-sufficiency. Knowing I can execute and publish high-quality solo research has been my rock throughout these tribulations. Second, vet collaborators carefully. I now approach research partnerships like hiring decisions, checking collaborators’ work, asking around, and taking time to decide on new endeavors. Third, always protect yourself. Before sharing ideas, I establish clear collaboration agreements. I settle matters in writing, documenting key conversations and milestones, as these records prove invaluable if things go sideways.除了证明自己的清白之外，我从中汲取的教训也重塑了我对待合作的态度。首先，要确保独立自主。我知道自己能够独立完成并发表高质量的研究成果，这在我经历这些磨难时给了我莫大的安慰。其次，要认真筛选合作者。我现在对待研究伙伴关系就像对待招聘决策一样，我会仔细审查合作者的工作，四处打听，并花时间认真考虑新的合作项目。第三，永远要保护自己。在分享想法之前，我会制定清晰的合作协议。我会将所有事项以书面形式记录下来，包括关键对话和里程碑事件，因为这些记录在出现问题时至关重要。 After 16 years in academia, I’ve become more selective about collaboration. It remains a joy and a blessing, but I’ve also learned how quickly “we” can turn wicked. The key is choosing your partnerships wisely and keeping “I” as a strong safety net.在学术界摸爬滚打了十六年后，我对合作变得更加谨慎。合作依然是一件乐事，也是一种恩赐，但我同时也体会到，“我们”这个概念很容易演变成有害的局面。关键在于明智地选择合作伙伴，并始终保持“我”作为坚实的后盾。Products & Materials  产品与材料New Products  新产品 A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.每周汇总有关新推出的仪器、设备和实验室材料的信息，这些信息可能对研究人员有用。InVivoSIM™ Bio X Cell is expanding its InVivoSIM™ line with the launch of biosimilar peptides, a new category of in vivo-ready research tools. The first release includes semaglutide, dulaglutide, and tirzepatide biosimilars, providing powerful reagents for investigating type 2 diabetes, obesity, and related conditions. These recombinant peptides reproduce the activity of clinically validated incretin agonists, enabling detailed studies of glucose regulation, appetite control, and metabolic signaling. Their utility also extends to broader areas of translational research, including cardiovascular health, kidney disease, and neurodegeneration. As the initial installment in Bio X Cell’s peptide platform, InVivoSIM™ biosimilar peptides deliver the ultra-pure quality, reproducibility, and consistency trusted across Bio X Cell’s antibody catalog, supporting reliable results from early-stage discovery through advanced preclinical studies.Bio X Cell 正在扩展其 InVivoSIM™ 产品线，推出生物类似肽，这是一种全新的体内研究工具。首批产品包括索玛鲁肽、度拉糖肽和替拉帕肽生物类似药，为研究 2 型糖尿病、肥胖症及相关疾病提供了强大的试剂。这些重组肽能够重现经临床验证的肠促胰岛素激动剂的活性，从而可以对葡萄糖调节、食欲控制和代谢信号传导进行深入研究。它们的用途还扩展到更广泛的转化研究领域，包括心血管健康、肾脏疾病和神经退行性疾病。作为 Bio X Cell 肽平台的首个产品，InVivoSIM™ 生物类似肽秉承了 Bio X Cell 抗体产品系列一贯的超纯品质、可重复性和一致性，为从早期发现到高级临床前研究的各个阶段提供可靠的研究结果。SCIEX BioPhase 8800 The SCIEX BioPhase 8800 system harnesses new native fluorescence detection for protein-based CE assays. To ensure drug safety and efficacy, multiple critical quality attributes such as purity, fragmentation, aggregation, and post-translational modifications need to be well-characterized and monitored. Assays like CE-SDS and cIEF offer automated and quantitative quality assessments of protein therapeutics and are routinely used throughout the drug development process and as a product release test. Adding native fluorescence detection elevates these gold standard assays to improve confidence in data and accelerate the drug development pipeline. Reduce the noise and see low abundant peaks more clearly with a clean background. Higher signal intensity and a stable baseline are obtained through reduced stray light, higher transmissions, and eliminated background media interference in the capillary. Accelerate your data analysis and get a stable baseline for faster, more confident, and easier peak integration and accurate results. Simplify sample preparation and eliminate the need for complex protein-dye conjugation. Native detection relies on the naturally existing aromatic amino acids in the protein, eliminating the dye labeling process. The system achieves up to a 10x increase in sensitivity for CE-SDS and cIEF assays.SCIEX BioPhase 8800 系统采用新型天然荧光检测技术，适用于基于蛋白质的毛细管电泳 (CE) 分析。为确保药物的安全性和有效性，纯度、片段化、聚集和翻译后修饰等多种关键质量属性需要进行充分的表征和监测。CE-SDS 和 cIEF 等分析方法可对蛋白质治疗药物进行自动化定量质量评估，并广泛应用于药物研发流程以及产品放行检测。添加天然荧光检测技术可提升这些金标准分析方法的性能，从而提高数据可信度并加速药物研发进程。该系统可降低噪声，使低丰度峰更清晰地呈现，并拥有纯净的背景。通过减少杂散光、提高透射率以及消除毛细管内背景介质的干扰，可获得更高的信号强度和更稳定的基线。该系统可加快数据分析速度，获得稳定的基线，从而实现更快、更可靠、更便捷的峰积分，并获得更准确的结果。此外，该系统还简化了样品制备，无需复杂的蛋白质-染料偶联。天然检测技术利用蛋白质中天然存在的芳香族氨基酸，无需染料标记。该系统可使 CE-SDS 和 cIEF 检测的灵敏度提高 10 倍。Micro Spargers  微型喷射器 Biotech Fluidics has launched a range of micro spargers engineered to significantly reduce bubble size and increase gas transfer and volumetric mass transfer coefficient (kLa), resulting in reduced gas consumption and improved upstream reactor yields. A micro sparger is a device that introduces a gas such as air, oxygen, or carbon dioxide into a liquid by creating very small bubbles. These devices, typically made from sintered porous materials like stainless steel, create tiny bubbles, which increases the surface area for gas-liquid contact, leading to more efficient mass transfer and enabling processes like aeration and fermentation. Biotech Fluidics has teamed up with MOTT Corporation to offer micro spargers for bioreactor applications that efficiently dissolve gases, promote cell growth, and provide agitation. These micro spargers have proven to increase benchtop laboratory bioreactor and fermenter mass transfer rates by 100% to 400% over standard drilled pipes or single-opening dip tubes. Biotech Fluidics offers a wide variety of porous metal sparger tips for laboratory and pilot scale bioreactors and fermenters. With media grades ranging from 2 pm to 15 pm, Biotech Fluidics can offer a micro sparger optimized to generate bubble sizes, which are optimal for your specific media, organism, and mass transfer requirements. Whatever your bioreactor application, there is a micro sparger tip optimized for your needs.Biotech Fluidics 公司推出了一系列微型曝气器，旨在显著减小气泡尺寸，提高气体传递效率和体积传质系数（kLa），从而降低气体消耗并提高上游反应器的产量。微型曝气器是一种通过产生极小气泡将空气、氧气或二氧化碳等气体引入液体的装置。这些装置通常由不锈钢等烧结多孔材料制成，产生的微小气泡增加了气液接触的表面积，从而提高了传质效率，并促进了曝气和发酵等过程。Biotech Fluidics 公司与 MOTT 公司合作，为生物反应器应用提供微型曝气器，这些曝气器能够高效溶解气体、促进细胞生长并提供搅拌。经证实，与标准钻孔管或单开口浸入管相比，这些微型曝气器可将台式实验室生物反应器和发酵罐的传质速率提高 100%至 400%。 Biotech Fluidics 提供种类繁多的多孔金属曝气喷嘴，适用于实验室和中试规模的生物反应器和发酵罐。Biotech Fluidics 的培养基粒径范围从 2 μm 到 15 μm，可提供针对特定培养基、微生物和传质需求优化的微型曝气喷嘴，以产生最佳气泡尺寸。无论您的生物反应器应用是什么，总有一款微型曝气喷嘴能够满足您的需求。Mechanical Pipettes  机械移液器 Eppendorf, a leading international life science company that develops, manufactures, and distributes instruments, consumables, and services for use in laboratories around the world, announced the commercial launch of the Eppendorf Research 3 neo, designed to deliver accurate and precise results for accelerated volume selection and optimized ergonomics. The durable pipette is highly flexible, allowing users to switch between two volume settings to easily speed up or fine-tune volume changes, with a new volume lock feature that prevents unintentional volume changes. Further adjustable settings allow the pipette to accommodate different liquid types, tip geometries, reverse pipetting, and altitudes, ensuring optimal accuracy across various applications without the need for recalibration. The use of ColorTag changeable pipette marking rings provides a reversible labeling solution to further increase versatility. Constructed from high-quality materials and subjected to extensive testing, the new mechanical air-cushion pipette delivers high performance, consistently beyond the ISO 8655 test limits when used with epT.I.P.S.® pipette tips. Manufactured in an ISO 14001 certified facility powered by renewable energy, the new pipettes refect Eppendorf’s commitment to sustainability. The Research 3 neo comes in recycled and recyclable packs, and is compatible with BioBased pipette tips made of 100% biobased polypropylene following a massbalance approach, further reducing environmental impact.Eppendorf 是一家领先的国际生命科学公司，致力于为全球实验室开发、制造和分销仪器、耗材和服务。该公司宣布正式推出 Eppendorf Research 3 neo 移液器，旨在提供精准的移液结果，加快移液量选择速度，并优化人体工学设计。这款耐用的移液器具有高度灵活性，用户可在两种移液量设置之间轻松切换，从而快速或微调移液量。此外，新增的移液量锁定功能可防止意外的移液量变化。其他可调节设置使移液器能够适应不同的液体类型、吸头几何形状、反向移液和海拔高度，确保在各种应用中都能达到最佳精度，无需重新校准。使用 ColorTag 可更换移液器标记环，可实现可逆标记，进一步提升了移液器的多功能性。这款新型机械气垫移液器采用优质材料制造，并经过广泛测试，与 epT.IPS®移液器吸头配合使用时，性能始终优于 ISO 8655 测试限值。这款新型移液器在通过 ISO 14001 认证且采用可再生能源的工厂生产，体现了爱本德对可持续发展的承诺。Research 3 neo 采用可回收包装，并兼容采用 100% 生物基聚丙烯制成的 BioBased 移液器吸头（该吸头采用质量平衡法生产），进一步降低了对环境的影响。Droplet Digital PCR Platforms液滴数字 PCR 平台 The newly introduced instruments include Bio-Rad’s QX Continuum™ ddPCR system along with the QX700™ series of ddPCR platforms, acquired as part of the company’s recently completed acquisition of digital PCR developer Stilla Technologies. Together with Bio-Rad’s existing line of ddPCR systems, the expanded product portfolio, including over 400,000 assays, offers the most comprehensive line of digital PCR products for life science research and diagnostic applications. The end-to-end solutions feature industry-leading absolute quantification, high precision, and advanced multiplexing capabilities, combined with streamlined and simplified workflows. The QX Continuum™ ddPCR system is designed for translational research applications. It features qPCR-like workflow offering simplicity, performance, and flexibility in an all-in-one configuration with four-color multiplexing and up to eight discrete thermal profiles per plate. The QX700™ series consists of three new ddPCR instruments designed for academic research, environmental testing, cell and gene therapy, and biopharma quality control workflows. The systems enable seven-color multiplexing and have the capacity to process over 700 samples per day, with minimal input volume, continuous loading capability, and easy-to-use software for streamlined data interpretation.新推出的仪器包括 Bio-Rad 的 QX Continuum™ ddPCR 系统以及 QX700™系列 ddPCR 平台，后者是该公司近期完成对数字 PCR 开发商 Stilla Technologies 收购的一部分。结合 Bio-Rad 现有的 ddPCR 系统产品线，扩展后的产品组合（包含超过 40 万种检测方法）为生命科学研究和诊断应用提供了最全面的数字 PCR 产品线。这些端到端解决方案具有业界领先的绝对定量、高精度和先进的多重检测功能，并结合了精简高效的工作流程。QX Continuum™ ddPCR 系统专为转化研究应用而设计，其工作流程类似于 qPCR，在一体化配置中兼具简便性、高性能和灵活性，支持四色多重检测，每个反应板最多可设置八个独立的热循环程序。QX700™系列包含三款全新的 ddPCR 仪器，分别适用于学术研究、环境检测、细胞和基因治疗以及生物制药质量控制工作流程。该系统可实现七色复用，每天可处理超过 700 个样本，输入量极少，具有连续加载能力，并配备易于使用的软件，可简化数据解读。

Elementary school-aged children enrolled in remote learning experienced greater behavioral, learning-related, and sleep difficulties compared with children receiving in-person instruction, according to the findings of a new study. Millions of children spent months, even more than a year, attending school virtually from kitchen tables, bedrooms and laptops during the pandemic. And this shift to computer-based learning may have led to negative consequences for younger kids, suggests a new Michigan Medicine study of a sample of families in Michigan. Elementary school-aged children enrolled in remote learning experienced greater behavioral, learning-related, and sleep difficulties compared with children receiving in-person instruction, according to the findings in the Journal of Developmental and Behavioral Pediatrics. Researchers surveyed roughly 300 parents with children ages 5 to 10 -- ranging from kindergarten to fifth grade -- across the state between February and March 2021. "In the early days of learning about how the virus spread and who was at risk, everyone made the best decisions they could with the information they had," said lead author Kimberley Levitt, M.D., developmental behavioral pediatrician at University of Michigan Health C.S. Mott Children's Hospital and Michigan Medicine researcher. "We wanted to explore differences in parent and child well-being at a time when some school districts had returned to in-person school, while others remained remote or hybrid." An estimated more than 55 million students in the U.S. were impacted by a change in school formats during spring 2020 of the COVID-19 pandemic, with many in fully remote school that school year. Study authors said they focused on younger children who are still building foundational academic skills and require more adult support during instruction. "We're now seeing the manifestation of these disruptions in families' lives and how different school formats affected our kids, not only academically but emotionally and socially," Levitt said. "Our findings reinforce challenges families faced during the pandemic and suggest children in virtual school had more behavioral issues at home, social challenges with peers and may have potentially been less motivated to learn." The new study is among few specifically examining how family well-being varied by school format. Researchers compared several areas of health, including: Behavior Problems Children in remote school showed significantly more signs of hyperactivity, peer problems and overall behavior issues compared to those attending in-person school, the study suggests. Among potential factors: Fast-changing demands and expectations as they navigated new school platforms and workloads. Adjusting to interactions with teachers and classes through screens. Being home for extended periods of time with fewer outlets to let off energy and less interaction with positive role models at school. "COVID dramatically disrupted schedules," Levitt said. "There's a certain amount of comfort and safety in knowing what to expect and having routines to fall back on. In general, any sudden changes to routines can trigger stress and emotional dysregulation in kids." "We want to be mindful of changes in family support systems and how we can support those children and families moving forward." School Experiences School was an overall more challenging experience for remote learners, researchers found. Virtual school attendees were less likely to be academically motivated or socially engaged and more likely to show defiance and resistance in doing schoolwork. "Remote learners appeared to be less excited about learning," Levitt said. "We know that children's enthusiasm and engagement in school helps predict how they cope with academic challenges throughout the year." Families in both hybrid school and remote formats also reported children having more difficulties with socially relevant learning. Parents of remote learners were less likely to report that the teacher knew their child well, the child knew their classmates well, was motivated to get ready for school in the morning, has enough opportunities to socialize, or has a best friend. "Some kids experienced a loss in the school setting beyond academics. At these ages, many children develop friendships or even get a new best friend, hallmark childhood experiences," Levitt said. "Children often build a sense of community, identity and independence from parents through classroom environments. But some children may have missed out on opportunities to further develop social skills through school interactions." Sleep Challenges Sleep issues were also common among the remote learning population. Kids ages five to 10 who attended virtual school were falling asleep later and were more likely to co- sleep with parents than those attending classes in person. Compared to before the pandemic, about a third of parents said their child took longer to fall asleep, about a seventh reported more overnight awakenings, and more than a fifth said their child had more nightmares. Among potential explanations: Greater anxiety and stress, increased screen time and exposure to certain types of media exposure or possibly increased family conflicts. "We can't say for certain why these sleep disruptions are more prevalent among kids who attended remote school. There are several possible factors at play," Levitt said. "Providers should consider tailoring interventions for families who would benefit from a sleep hygiene reset. We know disrupted and poor sleep can affect all areas of health, including mood, behavior and both physical and developmental growth as well as academic performance." Potential Disparities Researchers also looked at how school format related challenges differed for families with material hardships and stressors during the pandemic, such as food or housing insecurity, and whether structural inequities may have led to a greater burden of stress for underrepresented minorities. Nearly a third of families surveyed included families from underrepresented racial or ethnic minorities. Underrepresented minority children were more likely to attend a remote school format than non-Hispanic white children, lining up with other studies. Surprisingly, associations between remote learning and behavior difficulties were stronger for children without material hardships, researchers found. "It's possible that families with material hardships may have more emotional and behavioral challenges at baseline associated with chronic poverty and structural and social inequities," Levitt said. "Children with material hardships showed more behavior challenges overall, but less associated with school format. Parents may not have detected a noticeable difference in the home setting during remote learning, but we need further studies to understand how to better support these families." Parent stress Researchers didn't find any differences in parent depression or stress based on children's school format, but more than two fifths of parents overall reported elevated depressive symptoms. But parents in previous studies have reported worsening mental health and more negative mood following COVID-19 associated restrictions. Authors note that providers may consider screening parents for mental health concerns and material hardships in order to identify those who could benefit from community mental health resources and social work assistance. "Children being home more due to remote learning was among several factors that likely impacted parental stress," said senior author Jenny Radesky M.D., a developmental behavioral pediatrician at Mott and researcher at Michigan Medicine. "Many parents in our sample reported material hardships, such as poverty, job loss, and food insecurity and reported more parent-child conflict. We heard this from families we treat at Michigan Medicine, but our survey showed that the experience was widespread throughout Michigan. "This school year, we hoped that things would improve with consistent in-person learning and increased educational funding," she added. "However, some children are still struggling behaviorally, and unfortunately, we are hearing that schools are not able to staff positions that support social-emotional health. We hope these results reinforce how important it is for schools to receive the support they need, so kids can heal after two challenging years." Additional authors include Tiffany Munzer M.D., Chioma Torres M.D., Alexandria Schaller B.A. and Harlan McCaffery M.S., all of U-M.