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实验性方法利用人工智能消除mRNA疫苗的冷链储存需求Experimental approach uses AI to eliminate cold storage for mRNA vaccines

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10月7日 - 在关于人工智能可能灭绝人类的种种悲观预测之中,今天我们重点介绍两项利用该技术实现潜在医学进展的研究。我们还将报道一项细胞层面的发现,解释烟草烟雾暴露如何导致肺癌。

Oct 7 - With all the dire predictions about AI's potential to wipe out humanity today we highlight two studies that use the technology for potential medical advances. We also report on a discovery at the cellular level that explains how tobacco smoke exposure can lead to lung cancer.

利用人工智能,研究人员可能找到了一种方法,使基于mRNA技术的疫苗(如Moderna和辉瑞的新冠疫苗)能够在室温下保存,这将降低成本,并使这些疫苗在无法实现超低温保存的地区也能使用。

Using artificial intelligence, researchers may have found a way to make vaccines based on mRNA technology, such as Moderna's and Pfizer's COVID shots, storable at room temperature, which would lower costs and make them available in regions where ultra-cold storage is not possible.

目前,mRNA疫苗(包括Moderna的新流感疫苗)必须在极低温度下保存,通常在华氏-40度至-123度(摄氏-40度至-86度)之间。这是因为信使RNA极其脆弱,在较高温度下容易分解。

Presently, mRNA vaccines, including Moderna's new flu shot, must be stored at extremely low temperatures, typically ranging from -40 to -123 degrees Fahrenheit (-40 to -86 Celsius). That is because messenger RNA is extremely fragile and breaks down easily at higher temperatures.

在人工智能的帮助下,研究人员调整了疫苗中携带mRNA的脂质纳米颗粒的配方,使这些颗粒更耐热。

With help from artificial intelligence, researchers tweaked the formulation of the lipid nanoparticles that carry the mRNA in the vaccines, making the particles more heat-resistant.

根据发表在《自然·生物技术》上的一份报告,采用这种方法,他们配制的疫苗即使在室温下保存长达一年,或在华氏近100度下保存两个月,仍能保持稳定。接种了这些颗粒(即使经过长期保存)的小鼠,其免疫反应与接种了由类似Moderna原始配方的脂质纳米颗粒携带的疫苗的小鼠相当。

Using this approach, they formulated vaccines that could remain stable even when stored at room temperature for up to a year, or at nearly 100 degrees Fahrenheit for two months, according to a report published in Nature Biotechnology Mice that were vaccinated with these particles, even after long-term storage, showed equivalent immune responses to mice that received vaccines carried by lipid nanoparticles similar to the original formulation used by Moderna.

研究人员在报告中指出:“冷链要求在整个产品生命周期中增加了大量基础设施成本,包括专用包装、超低温储存、温控运输和持续监测。”他们补充道,耐高温疫苗可将储存成本降低多达86%。

“Cold-chain requirements add considerable infrastructure costs throughout the product life cycle, including specialized packaging, ultra-cold storage, temperature-controlled transport and continuous monitoring,” the researchers noted in their report. Vaccines that tolerate higher temperatures could reduce storage costs by up to 86%, they added.

“我们的方法不仅拓宽了mRNA疫苗的应用,还拓宽了治疗药物或先进药物递送平台(如控释微粒或微针贴片)的应用,这要求制剂要么处于固态,要么在较高温度下保持稳定,”麻省理工学院(MIT)研究负责人田锦碧在一份声明中表示。

“Our approach broadens the application of not only mRNA vaccines, but also therapeutics or advanced drug-delivery platforms like controlled-release particles or microneedle patches, which requires the formulation to either be in solid state or to be stable at higher temperature,” study leader Jinbi Tian of MIT said in a statement.

根据《心肺移植杂志》上的一份报告,人工智能可能提高医生在无需手术的情况下检测心脏移植排斥反应的能力,且似乎比标准血液检测更准确。诊断心脏移植排斥反应的当前金标准是通过手术切除一小块心肌,然后在显微镜下检查是否有炎症和其他变化。

AI may improve doctors' ability to detect heart transplant rejection without surgery and appeared to be more accurate than standard blood tests, according to a report in Journal of Heart and Lung Transplantation The current gold standard for diagnosing heart transplant rejection is the surgical removal of a small piece of heart muscle, which is then examined under a microscope for inflammation and other changes.

研究人员表示,某些常用的血液检测有助于识别排斥反应,但经常产生假阳性结果,导致不必要的活检。

Certain commonly used blood tests can help identify rejection but often produce false-positive test results, which lead to unnecessary biopsies, the researchers said.

研究团队利用389名成年心脏移植受者的数据,训练人工智能模型通过检测到的5000多份心电图读数中的模式来识别排斥反应,并将该信息添加到血液检测结果中。

Using data from 389 adult heart transplant recipients, the research team trained artificial intelligence models to recognize rejection using patterns detected in more than 5,000 electrocardiography readings and to add that information to blood test results.

在另一组38名男性和女性心脏移植受者中,研究人员发现该模型正确识别了100%未发生排斥反应的患者。

In a different group of 38 male and female heart transplant recipients, the researchers found the model correctly identified 100% of patients who were not experiencing rejection.

研究人员表示,单独进行血液检测会错误地将19名患者标记为可能需要活检。阴性检测结果的人真正没有排斥反应的概率为97%。

The blood tests alone would have incorrectly flagged 19 patients as potentially needing a biopsy, the researchers said. There was a 97% probability that a person with a negative test result truly did not have rejection.

“我们的结果表明,心电图包含大量生理信息,可用于大幅提高检测准确性,并使心脏移植排斥反应患者能够获得更早的诊断和治疗,”纽约大学格罗斯曼医学院研究负责人Lior Jankelson博士在一份声明中表示。

“Our results highlight that electrocardiograms contain an abundance of physiological information that can be used to substantially improve the accuracy of detection and enable earlier diagnosis and treatment for patients with cardiac transplant rejection,” study leader Dr. Lior Jankelson of the NYU Grossman School of Medicine said in a statement.

研究人员现在计划在多个移植中心的更多患者身上测试他们的模型。

The researchers now plan to test their model in more patients at several transplant centers.

根据最新研究,长期接触香烟烟雾会使维持和修复肺部的细胞更容易发生致癌基因改变。

Chronic exposure to cigarette smoke makes cells that maintain and repair the lungs more vulnerable to cancer-causing gene alterations, according to new research.

研究人员利用实验室培育的肺干细胞来源的“微型肺”,观察了肺细胞在长达六个月接触香烟烟雾中的化学物质和颗粒物过程中的变化。

Using mini-lungs grown from lung stem cells in the laboratory, researchers observed changes in lung cells over six months of exposure to chemicals and particles contained in cigarette smoke.

根据发表在《美国国家科学院院刊》(PNAS)上的一份报告,长期暴露改变了肺细胞的基因编程和基因活性,形成了独特的癌前状态;显著变化包括炎症和免疫信号通路以及参与程序性细胞死亡的基因受到抑制。

The chronic exposure altered gene programming and gene activity in the lung cells, creating distinct precancerous states, according to a report published in PNAS Among the notable changes was suppression of inflammatory and immune signaling pathways and genes involved in programmed cell death.

当研究人员引入两种常与吸烟相关肺癌相关的基因变异——KRAS和TP53时,发生改变的干细胞群体表现出了不同的反应。

When researchers introduced two gene variants commonly associated with smoking-related lung cancer, KRAS and TP53, the altered stem cell populations responded differently.

KRAS突变主要驱动源自所谓细支气管肺泡干细胞的细胞发展为肺腺癌,而肿瘤抑制基因TP53的缺失则导致源自基底干细胞的鳞状细胞癌。

KRAS mutations drove lung adenocarcinomas primarily from cells derived from so-called bronchioalveolar stem cells, while loss of the tumor suppressor gene TP53 produced squamous cell carcinomas derived from basal stem cells.

研究人员早已知晓KRAS和TP53等基因突变可驱动肺癌。但这些突变也可见于正常或癌前组织,这表明它们单独作用可能不足以启动癌症。

Researchers have long known that mutations in genes such as KRAS and TP53 can drive lung cancer. But the mutations are also seen in normal or precancerous tissue, suggesting that on their own, they may not be sufficient to start cancer.

为测试香烟烟雾暴露是否使细胞更易受癌症驱动突变转化,研究人员将暴露于烟雾的微型肺和未暴露的微型肺植入小鼠体内。

To test whether cigarette smoke exposure made the cells more susceptible to transformation by cancer-driving mutations, the researchers implanted smoke-exposed mini-lungs and unexposed mini-lungs in mice.

只有含有上述基因改变之一且暴露于烟雾的类器官形成了肿瘤。单纯的香烟烟雾暴露未产生肿瘤,将基因改变引入未暴露于烟雾的类器官中也未产生肿瘤。

Only the smoke-exposed organoids containing one of the genetic alterations formed tumors. Cigarette smoke exposure alone did not produce tumors, nor did introducing the genetic alterations into organoids not exposed to smoke.

研究结果帮助解释了环境暴露、化学变化和基因突变如何在非小细胞肺癌(最常见的肺癌类型)最早期共同作用,研究人员表示。

The findings help explain how environmental exposure, chemical changes and genetic mutations may work together during the earliest stages of non-small cell lung cancer, the most common type of lung cancer, the researchers said.

约翰斯·霍普金斯大学的研究负责人米歇尔·瓦兹对将这些知识与其他疗法结合,用于研发“帮助目前对治疗无反应的肿瘤更好响应”的药物前景感到兴奋。(欲免费在收件箱中接收完整通讯,请在此注册)

Study leader Michelle Vaz of Johns Hopkins University expressed excitement about the prospects of using this knowledge, in combination with other therapies, to come up with drugs that "help tumors that currently do not respond to treatment, respond better.”