2024年是颇为中国生化人值得记忆的一年。2024年恰逢中华人民共和国成立75周年、北京大学基础医学院建院70周年、刘思职院士诞辰120周年、童坦君院士诞辰90周年，而且即将迎来的2025年是《中国生物化学与分子生物学报》创刊40周年。在这些值得纪念的日子里，撰写此文，缅怀离我们而去的中国生物化学的老前辈。虽然他们离开了我们，但是他们的科学贡献永不消失，他们的科学精神永存光芒。他们的科学功绩映照出新中国生物化学学科取得的巨大成就，他们的科学精神映照出中国医学教育事业走过的蓬勃发展之路，他们的名字永远值得我们铭记。

刘思职（1904 ~1983），中国近代著名生物化学家、中国科学院学部委员。1904年出生于福建仙游，1921年考入厦门大学化学门，1924年转入上海大夏大学（现华东师范大学前身之一）。1925年大夏大学毕业后，赴美国西南大学学习，并于1926年获得西南大学理学学士学位。1926年进入美国堪萨斯大学攻读物理化学博士学位，1929年获得博士学位回到母校大夏大学任教。

1930年刘思职调入北京协和医学院生物化学系，担任系主任吴宪（1893 ~ 1959）的助手。1934年至1935年期间，曾赴德国威廉皇家研究院、英国剑桥大学访问。在协和医学院生物化学系工作期间，刘思职与吴宪及其他同事合作进行了蛋白质变性、免疫化学和超声波应用等方面的研究。吴宪、刘思职等首次在国际上阐明了可溶蛋白质在溶液中具有紧密的三维结构，确定了蛋白质变性的本质即为紧密结构向松散结构的转变过程。刘思职创造性地将化学平衡原理应用于抗体抗原体系当中，开辟了免疫化学领域的崭新局面。

1942年，协和医学院被侵华日军关闭后，刘思职转入北京大学医学院、理学院担任教授。1952年院系调整后，刘思职在北京医学院（现北京大学医学部）长期工作，多年担任北医生化学科负责人，直至退休。1956年刘思职被推选为中国生理科学会理事长，1957年当选为中国科学院生物学部委员。在北医生化工作期间，刘思职带领王世中进行了低级抗体研究，带领陈明、陈诗书和童坦君等进行了血氨毒性与代谢研究，带领董志伟和李刚等进行了免疫代谢相关研究。此外，刘思职还与医学史家李涛合作，对中国古代生物化学史进行了详尽考察。

……

2025年是《中国生物化学与分子生物学报》(以下简称《学报》)创刊40周年。40年前,时任中国生物化学会(现更名为“中国生物化学与分子生物学会”)常务理事、北京医学院生化系创建人之一的张昌颖教授在全国学术大会上提出“传播和普及科技的新概念、新理论、新技术是当务之急,学会应创建《生物化学杂志》”。这一提议获得了北京大学等全国大多数高校、医科院、军科院生化界前辈的响应,也得到了当时的彭瑞骢书记和马旭院长等校领导的鼎立支持,使得《学报》成功创刊。《学报》最初刊名为《生物化学杂志》,是中国生物化学与分子生物学会的会刊之一。《学报》由中国科学技术协会主管,中国生物化学与分子生物学会和北京大学共同主办。

我于2004年起任《学报》编委,后任副主编,2015年任主编至今,与《学报》一起走过了21年。在我写这篇文章时,我手边放着的是40年前出版的第一期杂志。翻看着这本纸张泛黄的杂志,看到许德珩先生 “希望生物化学杂志面向国家经济建设,促进学术交流更好的为实现四个现代化服务”以及周培源先生“齐心协力、积极奋斗,攀登生物化学世界最高峰”的题词,能够感受到两位先生对《学报》深深的期许;翻看着王应睐、邹承鲁、郑集、张龙翔前辈的贺信以及第一任主编张昌颖教授的发刊词,仿佛听到老先生们在说,《生物化学杂志》是属于中国生物化学会全体会员的,它将成为同行间学术交流的园地,也会成为我们向国际同行交流研究成果的一个窗口。这一期刊登的北京大学陈忠国先生“同步辐射在生物大分子结晶学中的应用”、中科院生物物理所王志珍和梁栋材先生“胰岛素分子结构与功能关系的复杂性”等文章,无疑代表了当时我国乃至全世界范围内该领域的最高学术水平。是这些先辈们的高瞻远瞩、辛勤付出,为《学报》奠定了坚实的基础,使其成为了中国科技工作者进行学术交流的平台。他们的奉献值得我们每一位后来者深深感激与铭记。

在纪念《学报》创刊40周年之际,我要感谢张昌颖教授、张廼蘅教授和贾弘褆教授三位前任主编。他们秉持着对科技前沿的敏锐洞察,对内容质量的严苛要求,不断探索创新,努力提升《学报》的影响力,使得《学报》能够不断发展壮大,成为众多科技工作者信赖的交流平台。

我要感谢广大的作者们,是你们用智慧和汗水撰写的一篇篇精彩稿件,为《学报》注入了源源不断的新鲜血液。你们在科研一线的探索成果、创新思路,通过《学报》得以广泛传播,推动着科技界的交流与进步。

我要感谢亲爱的读者们,你们的关注、阅读与反馈,是我们坚持下去的动力源泉。是你们让这本期刊的价值得以真正实现,让科技知识在更广的范围内生根发芽。

我要感谢我们的编委团队、审稿专家和编辑部工作人员,更是《学报》发展不可或缺的中坚力量。你们凭借着深厚的专业知识和严谨的治学态度,为《学报》发展出谋划策,为每一篇稿件严格把关。你们不辞辛劳,默默奉献,确保了《学报》的专业性与权威性。

回首《学报》的发展,我们既看到曾经的辉煌,取得的成绩,也感受到了面临的挑战。如何扩大影响力、吸引优秀稿源、提高引用率,以及如何利用AI等新技术的发展,都是需要我们认真考虑,积极应对的。

我们也将继续秉承老一辈创刊者的精神,坚持高质量发展的路线。一方面,我们会加强与国际科技界的交流合作,积极拓展国际传播渠道,让更多的国际读者了解我们的期刊;另一方面,我们会进一步提升期刊的数字化水平,利用先进的技术手段,为作者和读者提供更便捷、高效的服务。

我们相信,在全体人员的共同努力下,《学报》将在未来的40年乃至更长的时间里,继续书写辉煌篇章,为推动科技进步、促进知识传播发挥更为重要的作用。

最后,再次感谢所有为《学报》付出过努力的人们,让我们携手共进,迈向更加灿烂的明天！

东风送暖,满目春光。40年前的二月,由当时的中国生物化学会(现名中国生物化学与分子生物学会,以下简称“学会”)主办的高级学术刊物《生物化学杂志》(以下简称《杂志》,现名《中国生物化学与分子生物学报》,以下简称《学报》)创刊号问世,从此,学会有了自己主办的学术期刊。此前,虽然已有学会会刊《生化通讯》(现名《生命的化学》),但其当时作为学会的通讯刊物,只刊载学会活动信息及科普读物。此外,尽管当时国内已有生物化学相关领域的科技期刊——《生物化学与生物物理学学报》和《生物化学与生物物理进展》,但它们当初分别由中科院生物化学研究所、生物物理研究所主办,不属学会刊物。为适应我国生化事业蓬勃发展的需要,在1981年举行的第二次全国生化代表大会召开之际,理事会研究决定筹办《生物化学杂志》。历经三年筹备工作,由学会主办、北京医学院(现名北京大学医学部)承办的《生物化学杂志》在1985年创刊问世了。值此创刊40周年之际,特向《学报》主办单位中国生物化学与分子生物学会、北京大学及学会会员、编辑部表示祝贺;庆贺杂志创刊40周年！

百果园里桃千株,老少园丁齐灌注。

不惑之年又丰年,创新创优创一流。

值得注意的是,《杂志》创刊的首期刊载了中科院上海生物化学研究所、生物物理研究所、动物研究所及微生物研究所,以及军事医学科学院、北京大学、华东师范大学、上海第一医学院、哈尔滨医科大学等单位的原创科研论文,广泛涉及生物化学、生物物理学、化学、物理化学、生物学、微生物学、免疫学和肿瘤学,以及分子生物学和细胞生物学等领域。从《杂志》创刊号载文所涉及的多学科领域可以看出,当时《杂志》承办极其重视生命科学前沿学科及其交叉和融合,这与21世纪科学技术的发展趋势不谋而合。当代生命科学与生物技术领域的一个鲜明特征和发展趋势就是跨学科融合、互相转化,实现科学理论和技术创新。这种认识决定了《杂志》的学科特性和办刊方向。

中国科协是党和政府联系科技工作者的纽带。40年来,不论是《杂志》创建之初,还是更名为《中国生物化学与分子生物学报》之后,《杂志/学报》始终遵照主管单位中国科协有关规定及国家出版署的各项出版法规办刊,听党的话,严格按党“大力推进科学技术现代化”的要求,宣传党的“科教兴国”、“人才强国”和“创新驱动发展”等一系列重大战略方针,坚持 “科学技术是生产力”的科学思想,以实现“四个现代化”为动力,实施“宣传科学和传播科学,为祖国广大科技工作者服务,为祖国现代化建设服务”的指导原则,坚守办刊的思想性、科学性、先进性和实用性。尤其是在本世纪的前二十年里,伴随网络信息技术,特别是数字化发展势头的增长,《学报》编辑部完成了全版、全程数字化工程,实现了杂志内容在数字平台上的公开和共享,以及作者/读者与编辑部在投稿、查询和检索过程中的互动,广受作者/读者赞赏。《学报》普及范围越来越广,已成为公认的具有业内影响力的杂志之一,入选国家新闻出版广电总局第一批认定学术期刊,获中国科协优秀科技期刊奖、第二届百种中国杰出学术期刊奖,并被国内外十多家数据库全文收录。40年来《学报》的成绩归功于学会所辖的全国各专业领域,包括生物科学、医学科学、中医药学、工业、农业、海洋、高等生物医学教育等领域的科技工作者,是他们以优异的创作、热情的参与为期刊的创新和发展做出了贡献。当然,《学报》取得的成绩还应归功于创建杂志的前辈们,是他们为后生铺路,奠定了可持续发展的坚实基础。此外,《学报》的进步和发展还应归功于编辑部及其上级单位,编辑们兢兢业业和精湛的编辑、出版技能及创新意识使得期刊愈加生动和多姿多彩;上级单位(包括学会、北京大学以及北京大学医学部和基础医学院)的人力、物质资源是杂志可持续发展的根本保证。谨向上述人员、单位表示敬意和致谢！

伴随祖国经济腾飞,我国科技队伍规模和科研成果大幅扩大,已成为世界上规模最大、发展速度最快的科技论文发表市场,“以世界一流科技期刊建设带动我国科技期刊的整体发展”已成为国内共识。2019年,中国科协、中宣部、教育部、科技部联合发布的《关于深化改革 培育世界一流科技期刊的意见》(以下简称《意见》)是推动我国科技期刊改革发展的纲领性文件。《意见》提出了建设世界一流期刊的发展目标,打造一批在专业学科领域具有国际竞争力和影响力的一流科技期刊。有人主张,期刊的核心竞争力系由刊载论文的原创性、创新性和前沿性决定,而不是由语种和国别决定的。《中国科技期刊发展蓝皮书(2023)》也强调增强期刊对一流成果的承载能力。世界一流水准科研成果的载体其论文必须对学术、技术、产业等产生巨大影响,能够引领所涉领域,推动人类社会进步。《意见》中规划实现四项重点任务,其中包括“通过遴选一批优势学科、新兴交叉学科、战略前沿学科领域的优秀期刊”,“构建开放创新、协同融合的中国科技期刊体系”。由此可见,期刊对一流科研成果的承载能力与学科建设相关。著名生化前辈、《学报》首任主编张昌颖在发刊词中强调:“《生物化学杂志》创办的目的就是发展我国的生物化学(学科)。”另一位生化前辈郑集在创刊号的贺词中明确指出,《杂志》的“主要任务是刊载具有一定创造性的生化研究成果。”学会理事长王应睐和邹承鲁、张龙翔等著名老一辈科学家、教育家,以及时任人大常委会副委员长许德珩、北京大学校长周培源在他们给《杂志》创刊号的题词、贺词中也分别再三强调《杂志》要促进学术交流和学科建设,为实现祖国四个现代化服务。40年过去了,党中央号召“推进中国特色哲学社会科学体系、学术体系、话语体系建设”(引自“中共中央关于党的百年奋斗重大成就和历史经验的决议”),以及中国科协联合三部提出的“建设世界一流期刊的发展目标”与生化前辈创建《生物化学杂志》时的初衷完全一致;如果说有什么不同的话,现在我国已成为世界第二大经济体,我们的科研实力和科研产出快速提升,科技期刊也快速发展,实现建设世界一流科技期刊的任务更加紧迫了。时不可待,我们要学习、继承先辈科学家们发展学科、追求创新的精神,实现党和政府提出的建设世界一流期刊的发展目标。我们要创新创优,努力建设生化与分子生物学及其交叉学科领域创新科研成果的传播平台和宣传平台,建设在专业学科领域具有国际竞争力和影响力的一流科技期刊,为学科建设服务,为实现祖国社会主义现代化服务。

当今高等教育改革创新的重要领域是课程思政建设。生物化学是生命科学和医学教育的主干课程，作为生命科学的共同语言和前沿，其历史和当代的快速发展都为课程提供了丰富的思政素材。近年来，全国高校广泛展开的课程思政案例库编写、混合式教学优化思政效果等一系列教改探索，推动着生物化学课程思政建设不断前行。本刊2023年曾发表的空军军医大学赵晶等人的“生物化学TCA特色课程思政模式的构建与应用”一文，介绍了结构化生化课程思政体系的建设成果。然而，这些改革方案如何在教学实景中实施、如何在实践过程中对效果进行评价，进而进行改进和优化，对于实现课程思政建设各种方案的真正落地是亟待解决的课题。

为解决教学改革效果评价的难题，本期推出“TCA”课程思政模式的育人评价量规体系构建及应用”一文，旨在推动生物化学教学改革效果评价领域的发展。该文由武汉大学和空军军医大学合作完成，采用增值性评价、矩阵化评价、可迁移性评价等策略，对前文中提出的TCA课程思政体系在五年制医学本科生的实施质效进行了多维度多层次的量化评价性研究，初步建立了一个具有创新性的、兼具科学性和实用性的评价体系。该体系充分利用和优化了教育学和心理学中的评价工具，设计了一个针对思考质量、思维创造性、合作能力、思维迭代性、思维辩证性和岗位责任等6个方面的近百项指标的评价方案。应用该体系，肯定了“TCA”思政模式在引导学生建立正确的认知观、科学观和生命观等方面的积极作用，同时也证明了该思政模式的育人评价量规体系的可用性和有效性。虽然该体系是针对医学院校教学的评价，含有一些医学临床思维模式和职业特点的特定评价指标，但是也适用于理科、农科、工科等其他学科领域的生物化学思政教学评价，只需要在此基础上设计结合学科领域特色的个性化指标即可。

课程思政的育人效果是长期的，需要持之以恒的探索方可实现。在此过程中，借助科学的育人评价量规，教师方可及时知晓教学效果，促进教学决策的进一步优化。我们期待本文能够为国内的生物化学教学改革效果评价提供新的思路和方案，推动课程思政建设进程。

Antibiotic resistance is considered one of the most serious global threats to human health in the 21st century. The overuse of antibiotics has aggravated the development of bacterial resistance. Therefore, it is necessary to further study the mechanisms of bacterial resistance and explore new types of resistance and bacteriostatic strategies. This article provides an overview of the mechanisms of bacterial resistance and new antibacterial strategies for drug-resistant bacteria. It elaborates on the molecular mechanisms of three types of resistance: inherent resistance, acquired resistance and adaptive resistance. It also discusses new antibacterial strategies such as new antibacterial compound molecules, phage therapy, CRISPR-Cas system therapy and antisense therapy. This review aims to summarize the mechanisms of bacterial resistance and provide a reference for subsequent prevention and treatment of bacterial resistance.

Cellular senescence refers to the stable state of cell cycle arrest in which cells lose the ability of division and proliferation. Various intracellular and extracellular stimuli can induce cell senescence. Senescent cells exhibit multiple hallmarks, such as the upregulation of cell cycle inhibitor proteins p16^INK4a and p21^Cipl, DNA damage responses, and structural and metabolic alterations. Another major hallmark of senescent cells is that they express and secret a variety of factors, including cytokines, chemokines, growth factors, proteases, and other bioactive molecules, defined as the senescence-associated secretory phenotype (SASP). SASP factors exert multiple biological functions through the cell autonomous autocrine manner or cell non-autonomous paracrine fashion. In this review, we summarize the composition of SASP, and point out its high heterogeneity and dynamics. We then summarize the regulatory mechanisms of SASP at various levels including transcription, post-transcription, translation, post-translational modifications, and epigenetics. Afterwards, we summarize the various biological functions of SASP, including its beneficial effects in tumor suppression, tissue repair, and embryonic development, as well as its detrimental effects in inducing cell senescence, promoting tumor occurrence and development, age-related diseases, and organismal aging. We further discuss the potential applications of the SASP, which overview the senolytic therapy for selectively clearing senescent cells and senomorphic therapy for inhibiting SASP to intervene age and age-related diseases. Finally, we outline several challenges in identifying and detecting senescent cells and SASP factors in vivo, and provide some practical recommendations and new techniques to address these challenges.

Colorectal cancer ranks among the malignancies with high incidence and mortality rates, posing significant challenges to its prevention and treatment. In recent years, accumulating evidence has highlighted the critical involvement of deubiquitinases in the development and progression of colorectal cancer. Deubiquitinases meticulously remove ubiquitin moieties from proteins, thereby regulating protein stability, cellular signaling cascades, and gene expression, which in turn impacts key processes in tumor cells such as proliferation, survival, and metastasis. Deubiquitinases can influence the stability of cell cycle proteins, promoting cell cycle progression and accelerating cellular proliferation. Within the Wnt/β-catenin signaling pathway, deubiquitinases contribute to pathway hyperactivation by enhancing nuclear localization of β-catenin, a pivotal event in colorectal cancer initiation. Deubiquitinases also play a role in modulating the stability of immune checkpoint regulators, affecting the function of immune cells within the tumor microenvironment and facilitating immune evasion. Through regulation of transcription factor ubiquitination status, deubiquitinases impact target gene expression, promoting epithelial-mesenchymal transition, thereby augmenting colorectal cancer's invasive and metastatic potential. Moreover, deubiquitinases mediate chemoresistance in tumor cells by controlling the stability of apoptosis inhibitors, DNA repair enzymes, or drug efflux pumps.Given the critical role of deubiquitinases in colorectal cancer progression, the development of small molecule inhibitors targeting specific deubiquitinases has emerged as an attractive yet challenging field of research. Several inhibitors have demonstrated the capability to inhibit colorectal cancer cell growth and induce apoptosis in vitro and animal models. This review delves into the advancements in understanding the roles of deubiquitinases in colorectal cancer and discusses the application of small molecule inhibitors in colorectal cancer, providing insights for therapeutic strategies against this disease.

Endoplasmic reticulum stress (ERS) is a protective cellular response that occurs when cells face hypoxia or nutrient deprivation. It alleviates protein accumulation in the endoplasmic reticulum (ER) by the unfolded protein response. Unfolded or misfolded proteins that are not efficiently cleared by the unfolded protein response pathway are degraded by endoplasmic reticulum-phagy (ER-phagy), which is trigged by ERS to restore ER morphology. ER-phagy is mediated by ER-phagy receptors. In mammalian and yeast cells, various ER-phagy receptors exist that promote ER fragment formation, capture autophagic cargos and deliver them to autolysosomes for degradation. Each ER-phagy receptor has unique structural features that determine its mode of cargo capture. Additionally, ERS regulates ER-phagy by mediating the expression and phosphorylation of ER-phagy receptors. Research has shown that ERS-induced ER-phagy plays a crucial role in the pathogenesis of various human diseases. Therefore, elucidating the specific mechanisms underlying ERS-induced ER-phagy provides a theoretical basis for the prevention and treatment of ER-phagy-related diseases. Herein, we review the molecular mechanisms of ERS-induced ER-phagy mediated by ER-phagy receptors in mammals (FAM134B, RTN3L, SEC62, CCPG1) and yeasts (Atg39, Atg40, Erp1), as well as the connection between ERS-induced ER-phagy and human diseases such as neurodegenerative disorders and cancer, aiming to provide new strategies for the prevention and treatment of ER-phagy-related diseases.

Fostering virtue through education is the fundamental task of higher education, while the performance of ideological and political education is critical to achieving this task. “Biological Basis”, the core course of the bioengineering major which has a close relationship with other required courses, plays an important role in the professional training system. From the aspects of the necessity of ideological and political construction of “Biological Basis”, the exploration and design of ideological and political elements, the practice of ideological and political teaching, the optimization of ideological and political evaluation systems, and the effect of ideological and political teaching, this study elaborated on the constructing process of “Biological Basis”. The ideological and political elements were explored from celebrity anecdotes, daily life, research cases, and current events were further integrated into the teaching process of “Biological Basis” by the establishment of a teaching team and the online and offline mixed teaching methods, the development of case teaching, and the implementation of group discussion. Moreover, the ideological and political course teaching-effect evolution system was established. The results showed that students' interest in learning and the average score of the final paper significantly improved, from 66 points or less before the curriculum reform to 76 points after the reform. In addition, more than 92% of the students thought that the ideological and political teaching of “Biology Basis” was good, with a course satisfaction of 98%. The course's ideological and political teaching improves the quality of “Biology Basis”, achieving the goal of cultivating students' professional knowledge and comprehensive quality together. The construction experience of this course will provide some references for the ideological and political teaching and reform of other biology courses.

Cell cycle analysis is essential for determining the cell proliferation state, studying cell functions, and evaluating drug effects. Flow cytometry is a commonly used method for cell cycle detection, with propidium iodide (PI) being the most widely used fluorescein. Nevertheless, various factors may affect the test results. Additionally, comparing distributions of immune cell subpopulations across different cell cycle stages can provide valuable insights into immunological responses and disease conditions. In this research, the B16-F10 cell line was used to study the impact of three factors on PI staining-based cell cycle detection: fixation settings, sample preparation conditions, and software analysis. To fix cells, it is suggested to suspend 3 × 10⁶ cells in 300 μL of pre-cooled PBS, add 700 μL of 100% ethanol dropwise, fix overnight at 4℃ or -20℃, and collect at a low flow rate (400-600 events/s) to ensure collection of at least 3 000 singlets. Furthermore, dual-labeling with 5-ethynyl-2’-deoxyuridine (EdU) and PI can accurately distinguish cell cycle phases. And various immune cell subpopulations can be analyzed without cell sorting by combining surface marker staining with PI and Ki-67 staining. Here we review factors affecting cell cycle identification using the PI staining method and provide a standard operating protocol for the experiment. We established the method to combine EdU with PI for cell cycle detection and analysis of immune cell subpopulations, thus expanding the approaches for cell cycle detection.

Neural tube defects (NTDs) are common, severe, and complicated congenital malformations that are the result of the interaction and interplay of genetic, nutritional, and environmental factors. Maternal periconceptional folic acid (FA) supplementation is a significantly effective strategy for primary prevention of a proportion of NTDs. However, there still exists a portion of NTD cases that are intrinsically resistant to FA therapies, which are widely referred to as “FA-non-responsive NTDs” or “FA-resistant NTDs” . These diseases have a complex etiology, involving genetic, nutritional, environmental and maternal factors. This review integrates the genetic, nutritional, environmental and maternal risk factors associated with FA non-responsive NTDs and reveals the progress of research on their pathogenic mechanisms. Among them, the genetic factors cover three aspects: mouse mutants and strains, FA one-carbon metabolism genes, and key apoptosis genes, which provide possible genetic testing loci for prenatal diagnosis of these children. Nutritional factors concentrate on the roles of inositol and methionine, delineating their possible mechanisms of action and suggesting new directions for early nutritional interventions in NTDs management. In addition, this paper explores the possible mechanisms by which vitamin B12, a cofactor in the FA one-carbon metabolism, in FA-non-responsive NTDs development. We posit that a combination of FA and other vitamins may enhance treatment strategies for these malformations. At last, this paper also reviews the influence of environmental and maternal factors on FA non-responsive NTDs, aiming to provide health recommendations for early pregnancy for at-risk populations. In summary, this article reviews and evaluates research advancement concerning FA non-responsive NTD risk factors and pathogenesis, providing novel insights into the current prevention and treatment of this disease and related birth defects.

Induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have been proposed as an alternative source to primary mesenchymal stem cells(MSC), showing multiple advantages in disease treatment research. However, it remains unclear which disease type iMSCs are more suitable and whether they carry potential risks. This study utilized high-throughput sequencing data from public databases to compare iMSC with bone marrow-derived MSC (BM-MSC), adipose-derived MSC (AD-MSC), and umbilical cord-derived MSC (UC-MSC). Through various bioinformatics methods, including differential gene expression analysis, functional enrichment analysis, protein-protein interaction network analysis, and CMap database screening. The results indicated that iMSC possesses unique gene transcription characteristics, showing significant differences in gene expression compared to the three commonly used MSC types, particularly in genes related to neural and muscle development and immune regulation. Functional enrichment analysis of the differential genes further confirmed iMSC's potential advantages in treating neuro-related diseases, along with its lower immunogenicity but higher tumorigenic risk. Analysis using the CMap database identified potential gene targets and small molecule inhibitors to mitigate the tumorigenic risk of iMSC, providing possible strategies to reduce the risks associated with iMSC application. In summary, as a potential source for cell therapy, iMSC shows promising advantages in treating neurological diseases, but its safety needs to be validated through further experiments and clinical studies.

Protein methylation is a common post-translational modification in organisms. For a long time, research on protein methylation mainly focused on arginine and lysine, and there were few reports on histidine methylation. However, recent studies have emphasized that histidine methylation is also a widespread and highly conserved modification, occurring at the Nπ and Nτ sites of the histidine imidazole ring, catalyzed by specific protein histidine methyltransferases (PHMTs). Here, we review the history and significant advances in histidine methylation in recent years, particularly highlighting several known histidine methyltransferases. These methyltransferases, through specific molecular mechanisms, are responsible for precise methylation modifications on histidine residues, playing crucial roles in processes such as cell movement, tumor cell proliferation, and protein translation. Additionally, this article discusses the research methods for histidine methylation, especially the application of mass spectrometry, which plays a vital role in advancing histidine methylation research. Although the veil of histidine methylation is gradually being lifted, a complete understanding of this modification and its functional mechanisms still poses challenges. Therefore, this article also presents new insights into the current dilemmas in histidine methylation research and future research priorities, hoping to uncover more secrets of histidine methylation in the future. This could expand the protein methylation modification network and provide new perspectives and strategies for elucidating disease mechanisms and developing new therapeutic approaches.

With the acceleration of population aging, all kinds of cardiovascular diseases caused bycardiac aging have become a health problem that cannot be ignored. In the heart, about 95% of ATP come from the cardiomyocytes to maintain the pumping function. Mitochondrial dysfunction can lead to myocardial energy deficiency, cardiomyocytes damage and death, or myocardial senescence. Therefore, the intact function of mitochondria plays an important role in maintaining the normal function of the heart and is considered as a key feature of cardiac aging. This paper reviews cardiac aging and mitochondrial dysfunction, and mainly summarizes the characteristics of aging heart and the changes in mitochondrial structure and function of senescent cardiomyocytes. We focus on the five major factors leading to cardiac aging caused by mitochondrial dysfunction, including changes in the mitochondrial numbers and morphology, mitochondrial DNA mutations, mitochondrial quality control failures, mitochondrial enzyme changes, and mitochondria-related metabolites and stress signals changes. We also summarize the treatment methods and mechanism of cardiac aging by targeting mitochondria, anddiscuss the current status and future direction of mitochondrial therapy for cardiac aging.

Hypospadias, characterized by abnormal position of the urethral opening, is the second most common congenital anomaly in men. Its incidence is increasing year by year, and it has become the fourth largest birth defect disease in China. Not only does it bring both physical and psychological distress to the patients, but its surgical repair and long-term postoperative management also occupy a large amount of social economic and medical resources. Hypospadias can be isolated or present as a manifestation of some syndrome. At present, there are a variety of methods used to define and evaluate hypospadias, and it is imperative to develop a uniform classification standard to standardize care and surgical methods. In humans, the normal development of the penis structure has experienced an early androgen-independent stage and a late androgen-dependent sexual differentiation stage. In addition to genetic changes, endocrine or external environmental influences can cause damage or loss of the basic elements of penile development, which can induce hypospadias. Therefore, the disease is the result of genetic, endocrine and environmental factors and their interaction, with genetic factors generally considered to be more important than others. Based on different population cohorts, this paper elucidates the causes of hypospadias from the perspective of classical genetic variation, involving gene polymorphism, single nucleotide polymorphism and copy number variation of genes in normal biological processes such as growth differentiation of reproductive nodules, gonadal development and testis differentiation, androgen and estrogen production, etc. Moreover, the candidate genes related to human hypospadias are summarized. This paper will provide theoretical basis for the screening, intervention and clinical treatment of hypospadias, and contribute to improve the quality of birth population.