Volume 3  Issue 12

封面解读

George Fu Gao / Zepeng Xu

The ACE2-using coronaviruses (CoVs) have led to two outbreaks that profoundly affected the world, and continue to emerge as investigations deepen. A summarization of known ACE2-using CoVs indicates that they have a broad evolutionary distribution, spanning the genera Sarbecovirus, Merbecovirus, and Setracovirus. Meanwhile, these viruses also show a wide geographical distribution, demonstrating that ACE2-using CoVs are indeed a shared global concern. It is noteworthy that many CoVs were identified from previously collected samples and were proven to use ACE2 during re-investigations after the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reflecting the neglect of zoonotic CoVs. The cover is inspired by the Sinan—an ancient compass, one of China’s Four Great Inventions—which ancient Chinese used to determine the direction. It is meant to emphasize that although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern, continued surveillance on zoonotic CoVs remains necessary for prevention and early warning of the Next Pandemic.

All Papers

1. Ten scientific questions on regional immunity in the pulmonary and respiratory mucosal systems

hLife | 肺脏与呼吸道黏膜区域免疫十大科学问题

作者：第778次香山科学会议专家组

呼吸道相关疾病（包括感染、肺癌和过敏等）给全球人民生命健康和生活带来了严重威胁和重要影响。如何针对呼吸道疾病制定安全有效的预防和治疗策略，关键在于深入解析呼吸道黏膜特别是肺部的免疫应答，研发能够靶向肺部的药物或是诱导呼吸道黏膜区域免疫应答的保护性疫苗。第778次香山科学会议上，与会专家凝练出“肺脏与呼吸道黏膜区域免疫十大科学问题”，为突破当前防治瓶颈提供战略指导，这一战略框架将为我国抢占呼吸道疾病防治科技制高点、开发新一代疫苗和药物提供重要支撑。

引用：

778th Xiangshan Science Conference Expert Panel. Ten scientific questions on regional immunity in the pulmonary and respiratory mucosal systems. hLife 2025; 3: 569–572.

2. The 2025 Nobel Prize in Physiology or Medicine: The Treg, FoxP3 and STAT-regulated immune network

通讯作者：傅新元

The 2025 Nobel Prize in Physiology or Medicine, awarded for groundbreaking research on regulatory T cells (Tregs) and peripheral immune regulation, marks a major milestone in our understanding of immune homeostasis. At the same time, this achievement highlights the broader framework of signal transducer and activator of transcription (STAT) protein-mediated regulation, which orchestrates the differentiation and balance of multiple T helper (Th) cell subsets. Each Th lineage is guided by distinct cytokines that activate specific STAT proteins, thereby shaping the overall equilibrium of the peripheral immune system. Tregs—specialized CD4⁺ T cells that maintain immune tolerance through the STAT5–CD25–FoxP3 axis—represent a vital component of this system. Beyond Tregs, a number of other Th lineages collectively form the STAT-regulated immune network.

引用：

Fu XY. The 2025 Nobel Prize in Physiology or Medicine: The Treg, FoxP3, and STAT-regulated immune network. hLife 2025; 3: 573–575.

3. Pancreatic cancer cachexia: A systemic consequence of multi-organ interactions

hLife | 揭秘胰腺癌恶病质：一种由多器官失调引发的全身性“消耗疾病”

通讯作者：刘旭东、梁艳珊、吴文铭

胰腺癌恶病质是一种复杂的多因素综合征，主要表现为进行性体重下降、骨骼肌和脂肪组织丧失以及系统性炎症。在超过60%的胰腺癌患者中可见其发生，显著降低了患者的体能，削弱了其对治疗的耐受性，并缩短了总体生存期。与单纯的饥饿不同，恶病质无法通过常规营养支持完全逆转，而目前临床上尚无针对这一种高致命性“消耗性疾病”的有效治疗手段。本文全面而深入地总结了胰腺癌恶病质的系统性本质，指出其是一种由肿瘤与机体多个器官之间相互作用驱动的全身性疾病。在未来的研究与临床中，呼吁学者采取跨学科整合策略，将肿瘤学、代谢学、免疫学和神经科学有机结合，深入探索胰腺癌恶病质的本质机制。这些新见解有望推动临床实践的转变，让患者切实获益。

引用：

Xiao A, Feng Y, Yin B, et al. Pancreatic cancer cachexia: A systemic consequence of multi-organ interactions. hLife 2025; 3: 576–614.

4. ACE2-using coronaviruses: A global concern

通讯作者：刘科芳、高福

Recently, several studies have reported Merbecoviruses from bat and mink using angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. These reports raise global concern and highlight the significance of constant surveillance for animal coronaviruses (CoVs). Since the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, scientists have characterized various animal CoVs that use ACE2 as a receptor. During the coronavirus disease 2019 (COVID-19) pandemic, more animal CoVs from all over the world have been reinvestigated and found to utilize ACE2 as a receptor. Here, we briefly summarize the characteristics of ACE2-bindingCoVs and discuss the mechanisms underlying the acquisition of ACE2-binding capabilities.

引用：

Xu Z, Lobato AC, Liu K, et al. ACE2-using coronaviruses: A global concern. hLife 2025; 3: 615-617.

5. A One Health perspective on the 2025 chikungunya outbreak in Guangdong province, China

hLife | 温州医科大学陆家海研究团队评述广东基孔肯雅热疫情：“同一健康”的启示与新策略

通讯作者：陆家海

2025年以来，广东省已报告超1万例基孔肯雅热确诊病例，其中佛山市病例占比最多。此前，虽然基孔肯雅热疫情已得到一定控制，但由于假期人员流动量大，以及台风暴雨恶劣天气的影响，使仍处于蚊媒活跃期的广东存在疫情持续传播的风险。面对这一复杂局面，任何单一部门的干预措施都难以有效应对，亟需采取协调一致的多部门协作方法以解决其传播的多层面问题。本文系统梳理了基孔肯雅热的全球以及广东疫情流行现状及其影响因素，并提出“同一健康”视角下蚊媒传染病的防控策略。

引用：

Guo C, Mishra N, Aouacheria A, et al. A One Health perspective on the 2025 chikungunya outbreak in Guangdong province, China. hLife 2025; 3: 618–620.

6. Mighty oaks from little acorns: High-quality genomes of underrepresented populations enhance health equity in precision medicine

hLife | 弥合鸿沟：高质量基因组资源助力代表性不足人群实现精准医疗与健康公平

通讯作者：刘超、唐任宽、何光林

本文从参考基因组序列完整性和群体遗传多样性两个维度出发，系统综述了测序技术的进步、参考基因组构建策略优化、大规模人群队列研究等在解析基因组复杂区域、鉴定人群特异性变异、重构人类群体演化历史等方面的重要进展。并进一步提出了若干未来研究方向，包括构建多元化族群参考基因组、完善社区参与式研究范式与数据主权保障体系，以及开发跨族群基因组资源整合分析工具链。

引用：

Wang M, Luo L, YehHY,etal. Mighty oaksfrom little acorns: High-quality genomes of underrepresented populations enhance health equity in precision medicine. hLife 2025; 3: 621–625.

7. Single-cell RNA sequencing profiles age-related transcriptional landscapes in human hair follicle cell

hLife | 探索头皮衰老：单细胞和时空测序绘制人毛囊老化分子图谱

通讯作者：徐凤萍，赖永贤

脱发、白发早生已不再是中老年人的 “专属困扰”，越来越多年轻人为这些问题所困扰。看似只是 “颜值问题” 的现象，其背后隐藏着皮肤衰老的深层信号——头皮毛囊干细胞及其生存微环境的功能衰退。本文通过单细胞 RNA 测序技术对人类头皮衰老的转录调控机制展开深入探索，旨在解读头皮毛囊衰老的奥秘，为未来研发精准有效的头皮抗衰疗法提供了重要的科学支撑。

引用：

Zhao Q, Ma R, Huang K, et al. Single-cell RNA sequencing profiles age-related transcriptional landscapes in human hair follicle cells. hLife 2025; 3: 626–646.

8. CHIKVdb: A comprehensive genomic resource for chikungunya virus surveillance and outbreak response

hLife | CHIKVdb：基孔肯雅病毒数据库助力疫情快速监测、识别和溯源

通讯作者：马俊才、吴林寰

基孔肯雅病毒（Chikungunya virus, CHIKV）是一种由伊蚊传播的重要虫媒病毒，可引起基孔肯雅热，其特征是严重且往往持续性的关节痛，对全球公共卫生造成重大负担。近年来，CHIKV 的暴发频率和地理范围均有所增加，凸显出加强基因组监测和快速疫情应对的迫切需求。然而，现有的公共CHIKV基因组数据库通常数据分散、注释不完整，且分析流程效率有待提高，限制了其在紧急情况下的应用价值。本研究团队开发了基孔肯雅病毒数据库(CHIKVdb，https://nmdc.cn/gcpathogen/chikv)。该资源整合了来自99个国家、跨越40年的8193条CHIKV核苷酸序列（涵盖五大宿主类型）以及10,637条蛋白质序列，旨在为当前及未来的疫情响应提供支撑。

引用：

Guo C, Fan G, Chen Q, et al. CHIKVdb: A comprehensive genomic resource for chikungunya virus surveillance and outbreak response. hLife 2025; 3: 647–650.

9. Cross-platform compatibility of a structure-guided chimeric MPXV immunogen delivered via circular RNA delivery

通讯作者：高福

The mpox outbreak was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on two separate occasions. Currently, the prevention and control of mpox face severe challenges, including sustained human-to-human transmission, increasing frequency and geographic distribution of mpox outbreaks, and ongoing viral adaptive evolution. To evaluate the cross-platform compatibility of the immunogen design strategy, this study applies a previously designed "four-in-one" immunogen, AMA-aB—comprising single-chain dimeric A35, M1, and truncated forms of A29 and B6—within a circRNA vaccine form. In this study, the AMA-aB immunogen, when delivered via a circRNA platform, elicits both potent cellular and humoral immune response and confers complete protection against lethal poxvirus challenge in mice. Take together, our findings highlights the cross-platform compatibility of the structure-guided “all-in-one” chimeric immunogen design strategy and emphasize the critical influences of delivery platform on shaping the magnitude and specificity of the antigen-specific immune responses.

引用：

Ding H, Wu J, Liu Z, et al. Cross-platform compatibility of a structure-guided chimeric mpox virus immunogen delivered via circular RNA delivery. hLife 2025; 3: 651–654.