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Progress in constitutive modeling of arterial wall tissue mechanics: from theoretical frameworks to clinical application. 动脉壁组织力学本构模型的研究进展:从理论框架到临床应用。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.pbiomolbio.2025.12.005
Qian Fan, Dezhong Qi, Qiang Xiao, Xiaoqiang Zhou

Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and the mechanical behavior of arterial wall tissue (AWT) is central to its initiation and progression. This review surveys advances in constitutive models of AWT over the past two decades, with the aim of improving understanding of vascular mechanics and informing clinical practice. Five major computational frameworks are evaluated-elastic, viscoelastic, hyperelastic, structural solid models, and growth and remodeling (G&R) models-which collectively provide insights into stress-strain relationships and mechanobiological interactions under physiological and pathological conditions. Simple elastic formulations cannot capture the intrinsic nonlinearity of AWT. Nonlinear elastic and pseudo-elastic models are better suited for large deformations and anisotropy, especially under cyclic loading. Viscoelastic models effectively represent time-dependent responses to pulsatile blood flow. Structural solid models, including layered anisotropic, equivalent homogeneous, and generalized structure tensor formulations, predict the mechanical behavior of individual wall layers with high fidelity. Extending beyond instantaneous mechanics, G&R models embed these constitutive relations within higher-level frameworks to simulate long-term adaptations to altered hemodynamics, such as hypertension, aneurysm progression, or vascular graft remodeling. Future research should focus on developing dynamic models that more accurately simulate pulsatile loading, refining the characterization of AWT heterogeneity and anisotropy, and establishing multiscale and multi-physics frameworks to connect cellular processes with tissue-level behavior. Integrating big data and machine learning offers additional potential for robust parameter identification and predictive modeling. In conclusion, this review provides a comprehensive evaluation of AWT constitutive modeling, from fundamental elasticity-based approaches to advanced G&R frameworks. By identifying limitations and outlining future directions, it highlights the role of biomechanics in advancing personalized medicine, improving CVD diagnosis and treatment, and promoting deeper understanding of disease mechanisms.

心血管疾病(CVD)是世界范围内死亡的主要原因,动脉壁组织(AWT)的力学行为是其发生和发展的核心。本文综述了过去二十年来AWT本构模型的进展,旨在提高对血管力学的理解并为临床实践提供信息。评估了五种主要的计算框架——弹性、粘弹性、超弹性、结构实体模型以及生长和重塑(G&R)模型——它们共同提供了对生理和病理条件下应力-应变关系和机械生物学相互作用的见解。简单的弹性公式无法捕捉到AWT的内在非线性。非线性弹性和伪弹性模型更适合于大变形和各向异性,特别是在循环加载下。粘弹性模型有效地表示脉动血流的时变响应。结构实体模型,包括层状各向异性、等效均质和广义结构张量公式,可以高保真地预测单个壁层的力学行为。超越瞬时力学,G&R模型将这些本构关系嵌入到更高层次的框架中,以模拟对改变的血流动力学的长期适应,如高血压、动脉瘤进展或血管移植重塑。未来的研究应侧重于开发更准确地模拟脉动载荷的动态模型,完善AWT异质性和各向异性的表征,建立多尺度和多物理框架,将细胞过程与组织水平行为联系起来。集成大数据和机器学习为鲁棒参数识别和预测建模提供了额外的潜力。总之,本综述提供了AWT本构建模的综合评价,从基本的基于弹性的方法到先进的G&R框架。通过识别局限性和概述未来方向,它突出了生物力学在推进个性化医疗,改善心血管疾病诊断和治疗以及促进更深层次理解疾病机制方面的作用。
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引用次数: 0
Field potential duration and its variability as essential parameters for revealing proarrhythmia: problematic aspects of analysis in cardiomyocytes derived from human pluripotent stem cells 场电位持续时间及其变异性作为揭示心律失常的基本参数:人类多能干细胞衍生的心肌细胞分析的问题方面。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-10 DOI: 10.1016/j.pbiomolbio.2025.12.004
Martin Král , Olga Švecová , Pavel Jurák , Josef Halámek , Milena Šimurdová , Jiří Šimurda , Markéta Bébarová
The microelectrode array (MEA) is an easy, high-throughput method, ideal for obtaining a large amount of data from excitable cells, including cardiomyocytes. However, the analysis can be problematic, especially the analysis of the field potential duration (FPD). Several factors, including the differentiation protocol, culture duration, recording settings, and signal processing, may influence the results. In this paper, we focused on the MEA recording settings, analysis, and evaluation of FPD from cardiomyocytes, especially those derived from human pluripotent stem cells (hPSC). By examining more than 120 original articles using MEA and any cardiac preparation, we detected an inconsistency in the acquisition setting. It is striking that only one-third of the studies provided complete information about filtering of the signal, even though this may substantially influence the shape of the signal and, thus, FPD. The performed analysis emphasizes a thorough inspection of both the ‘raw’ and filtered signals to estimate proper FPD values, as well as a careful determination of the relationship between FPD and cycle length before using any correction formula.
微电极阵列(MEA)是一种简单、高通量的方法,非常适合从包括心肌细胞在内的可兴奋细胞中获取大量数据。然而,分析可能存在问题,特别是对场电位持续时间(FPD)的分析。有几个因素,包括分化协议、培养持续时间、记录设置和信号处理,都可能影响结果。在本文中,我们着重于MEA记录设置,分析和评价心肌细胞,特别是来自人类多能干细胞(hPSC)的FPD。通过检查使用MEA和任何心脏准备的120多篇原创文章,我们发现了获取设置中的不一致。令人惊讶的是,只有三分之一的研究提供了关于信号滤波的完整信息,尽管这可能会极大地影响信号的形状,从而影响FPD。所执行的分析强调对“原始”信号和滤波信号进行彻底检查,以估计适当的FPD值,以及在使用任何校正公式之前仔细确定FPD与周期长度之间的关系。
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引用次数: 0
WATER Roles in Cells: Biological and Biophysical perspectives. 水在细胞中的作用:生物学和生物物理学的观点。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.pbiomolbio.2025.12.003
Eugenio Frixione, Lourdes Ruiz-Zamarripa

Water, elected as Molecule of the Year 2024 by the American Society for Biochemistry and Molecular Biology, is the substance in which life originated on this planet and became then involved in numerous cell functions of all animal and vegetal tissues, up to being the most abundant component of all living systems. Despite its importance, however, the various conditions and roles of water in the protoplasm are mostly absent in current cell biology textbooks and common related reviews, so the subject demands consideration of how it should be now taught to graduate students interested in biochemistry and molecular biology. The present paper offers an overview of how knowledge about water involvement in cell structure and function has evolved from the mid 19th century up to our time, starting with early microscopic inspections of living cells, proceeding next to the emergence of notions about water distribution within them, including its various particular behaviors in the protoplasm and the roles it plays in cell function, plus succinct notes about recent reports of experimental approaches with their results and particular views on the topic for different types of cells.

水被美国生物化学和分子生物学学会选为2024年度分子,是地球上生命起源的物质,随后参与了所有动物和植物组织的许多细胞功能,成为所有生命系统中最丰富的成分。然而,尽管它很重要,但在目前的细胞生物学教科书和常见的相关评论中,大部分都没有提到水在原生质中的各种条件和作用,因此,这门学科需要考虑如何教授给对生物化学和分子生物学感兴趣的研究生。本文概述了从19世纪中期到我们这个时代,关于水参与细胞结构和功能的知识是如何演变的,从早期的活细胞显微镜检查开始,接着是关于水在细胞内分布的概念的出现,包括它在原生质中的各种特殊行为及其在细胞功能中所起的作用。加上对最近的实验方法报告及其结果的简要说明,以及对不同类型细胞的主题的特定观点。
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引用次数: 0
Injectable hydrogel: A promising frontier in cancer therapy 注射水凝胶:癌症治疗的一个有前途的前沿。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.pbiomolbio.2025.12.002
Amirhamzeh Farajollahi
The past decade has seen growing interest in injectable hydrogels for cancer therapy due to their tunable polymer backbones and high chemical versatility. Researchers are engineering injectable hydrogel platforms for chemotherapy, immunotherapy, and combination regimens to overcome limitations of conventional treatments. These materials enable localized, targeted delivery by encapsulating anti-tumor agents within a gel matrix, allowing sustained and controlled release that boosts efficacy while reducing systemic side effects. This review summarizes methods for preparing injectable hydrogels and highlights their key applications in cancer treatment, including strategies for payload loading, release modulation, and site-specific administration. We discuss how hydrogel composition, crosslinking chemistry, and microstructure govern therapeutic performance and biocompatibility, and we survey designs that integrate immune modulators, chemotherapeutics, or multi-modal agents for synergistic effects. Remaining challenges—such as predictable degradation, scalable manufacturing, in vivo stability, and regulatory translation—are examined, along with opportunities for improving targeting, responsiveness, and combination-therapy compatibility. Finally, we outline research directions needed to accelerate clinical translation, including standardized characterization, long-term safety studies, and optimized delivery protocols. By consolidating recent advances and identifying gaps, this review aims to guide future development of injectable hydrogels that can meaningfully enhance therapeutic outcomes for cancer patients.
在过去的十年中,人们对可注射的水凝胶越来越感兴趣,因为它们具有可调节的聚合物骨架和高化学通用性。研究人员正在设计可注射的水凝胶平台,用于化疗、免疫治疗和联合治疗,以克服传统治疗的局限性。这些材料通过将抗肿瘤药物封装在凝胶基质中,实现局部靶向递送,允许持续和可控的释放,提高疗效,同时减少全身副作用。本文综述了制备可注射水凝胶的方法,并重点介绍了它们在癌症治疗中的关键应用,包括有效载荷、释放调节和部位特异性给药策略。我们讨论了水凝胶组成、交联化学和微观结构如何影响治疗性能和生物相容性,并调查了整合免疫调节剂、化疗药物或多模态药物的协同效应的设计。剩余的挑战,如可预测的降解、可扩展的制造、体内稳定性和调节翻译,以及改善靶向性、反应性和联合治疗兼容性的机会。最后,我们概述了加速临床转化所需的研究方向,包括标准化表征、长期安全性研究和优化的给药方案。通过巩固最近的进展和确定差距,本综述旨在指导可注射水凝胶的未来发展,从而有意义地提高癌症患者的治疗效果。
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引用次数: 0
Overcoming the warming bottleneck in animal vitrification: Volumetric heating and enabling technologies for reproductive cryobanking 克服动物玻璃化的变暖瓶颈:生殖冷冻银行的体积加热和使能技术。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.pbiomolbio.2025.11.003
Jesse Oluwaseun Ayantoye , Baigao Yang , Hang Zhang , Jianhua Dong , Xiaomeng Zhang , Haoran Song , Muhammad Shahzad , Hubdar Ali Kolachi , Osamede Henry Osaiyuwu , Pengcheng Wan , Hongmei Pan , Xueming Zhao
Reproductive cryopreservation via vitrification is vital for livestock breeding and biodiversity conservation, as it enables ice-free storage of gametes and embryos. However, success increasingly depends on achieving rapid, uniform warming to avoid devitrification: the critical warming rate (CWR) required is often orders of magnitude higher than the critical cooling rate (CCR). Conventional convective thawing (e.g., water baths) produces edge-to-core thermal gradients that can lead to lethal ice formation in larger or more complex samples. Suboptimal warming disrupts cellular ultrastructure, leading to meiotic spindle collapse, mitochondrial depolarization, reactive oxygen species production, DNA damage, and apoptosis. These changes manifest as impaired embryo development and the formation of necrotic tissue cores. Notably, lipid-rich porcine oocytes and embryos are particularly susceptible to recrystallization during slow warming, with higher fragmentation and lower viability than their bovine and ovine counterparts. This review synthesizes thermophysical principles underlying the CWR requirement and biological evidence of the warming bottleneck across animal systems. This thermophysical imbalance means that rewarming, rather than cooling, is the decisive barrier to successful vitrification. We then discuss emerging volumetric rewarming technologies that uniformly deliver energy: magnetic nanoparticle-induced nanowarming, laser-driven photothermal heating, dielectric (radiofrequency/microwave) rewarming, and ultrafast Joule (ohmic) heating. These methods have demonstrably exceeded CWR thresholds in embryos, tissues, and organs, improving cell survival and function. We also highlight enabling tools such as microfluidic cryoprotectant (CPA) handling, automated vitrification platforms, artificial intelligence (AI)-guided protocol optimization, and isochoric (constant-volume) vitrification, which collectively enhance reproducibility and scalability of cryopreservation workflows. In conclusion, integrating volumetric heating modalities with these engineering innovations promises to transform animal cryopreservation: uniformly rapid warming will improve immediate post-thaw viability and preserve biological integrity, enabling routine, large-scale germplasm banking for livestock production and conservation.
通过玻璃化冷冻保存生殖器官对牲畜育种和生物多样性保护至关重要,因为它可以实现配子和胚胎的无冰储存。然而,成功越来越依赖于实现快速、均匀的升温以避免脱硝:所需的临界升温速率(CWR)通常比临界冷却速率(CCR)高几个数量级。传统的对流解冻(例如水浴)会产生边缘到核心的热梯度,在较大或更复杂的样品中可能导致致命的冰形成。次优升温破坏细胞超微结构,导致减数分裂纺锤体崩溃、线粒体去极化、活性氧产生、DNA损伤和细胞凋亡。这些变化表现为胚胎发育受损和坏死组织核心的形成。值得注意的是,富含脂质的猪卵母细胞和胚胎在缓慢升温过程中特别容易再结晶,比牛和羊的卵母细胞和胚胎碎裂率更高,生存能力更低。这篇综述综合了动物系统中CWR要求的热物理原理和变暖瓶颈的生物学证据。这种热物理不平衡意味着再加热,而不是冷却,是玻璃化成功的决定性障碍。然后,我们讨论了新兴的均匀输送能量的体积再加热技术:磁性纳米颗粒诱导的纳米加热、激光驱动的光热加热、介电(射频/微波)再加热和超快焦耳(欧姆)加热。这些方法在胚胎、组织和器官中明显超过了CWR阈值,提高了细胞存活率和功能。我们还重点介绍了微流控冷冻保护剂(CPA)处理、自动玻璃化平台、人工智能(AI)引导的方案优化和等时(等体积)玻璃化等工具,这些工具共同提高了冷冻保存工作流程的可重复性和可扩展性。总之,将体积加热方式与这些工程创新相结合有望改变动物冷冻保存:均匀快速加热将提高解冻后立即的生存能力并保持生物完整性,为牲畜生产和保存提供常规、大规模的种质资源库。
{"title":"Overcoming the warming bottleneck in animal vitrification: Volumetric heating and enabling technologies for reproductive cryobanking","authors":"Jesse Oluwaseun Ayantoye ,&nbsp;Baigao Yang ,&nbsp;Hang Zhang ,&nbsp;Jianhua Dong ,&nbsp;Xiaomeng Zhang ,&nbsp;Haoran Song ,&nbsp;Muhammad Shahzad ,&nbsp;Hubdar Ali Kolachi ,&nbsp;Osamede Henry Osaiyuwu ,&nbsp;Pengcheng Wan ,&nbsp;Hongmei Pan ,&nbsp;Xueming Zhao","doi":"10.1016/j.pbiomolbio.2025.11.003","DOIUrl":"10.1016/j.pbiomolbio.2025.11.003","url":null,"abstract":"<div><div>Reproductive cryopreservation via vitrification is vital for livestock breeding and biodiversity conservation, as it enables ice-free storage of gametes and embryos. However, success increasingly depends on achieving rapid, uniform warming to avoid devitrification: the critical warming rate (CWR) required is often orders of magnitude higher than the critical cooling rate (CCR). Conventional convective thawing (e.g., water baths) produces edge-to-core thermal gradients that can lead to lethal ice formation in larger or more complex samples. Suboptimal warming disrupts cellular ultrastructure, leading to meiotic spindle collapse, mitochondrial depolarization, reactive oxygen species production, DNA damage, and apoptosis. These changes manifest as impaired embryo development and the formation of necrotic tissue cores. Notably, lipid-rich porcine oocytes and embryos are particularly susceptible to recrystallization during slow warming, with higher fragmentation and lower viability than their bovine and ovine counterparts. This review synthesizes thermophysical principles underlying the CWR requirement and biological evidence of the warming bottleneck across animal systems. This thermophysical imbalance means that rewarming, rather than cooling, is the decisive barrier to successful vitrification. We then discuss emerging volumetric rewarming technologies that uniformly deliver energy: magnetic nanoparticle-induced nanowarming, laser-driven photothermal heating, dielectric (radiofrequency/microwave) rewarming, and ultrafast Joule (ohmic) heating. These methods have demonstrably exceeded CWR thresholds in embryos, tissues, and organs, improving cell survival and function. We also highlight enabling tools such as microfluidic cryoprotectant (CPA) handling, automated vitrification platforms, artificial intelligence (AI)-guided protocol optimization, and isochoric (constant-volume) vitrification, which collectively enhance reproducibility and scalability of cryopreservation workflows. In conclusion, integrating volumetric heating modalities with these engineering innovations promises to transform animal cryopreservation: uniformly rapid warming will improve immediate post-thaw viability and preserve biological integrity, enabling routine, large-scale germplasm banking for livestock production and conservation.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 31-45"},"PeriodicalIF":4.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantum mechanics as a tool to decipher the mutational landscape of human disease 量子力学作为破译人类疾病突变景观的工具。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.pbiomolbio.2025.11.004
Eustathia-Irene Zavitsanou , Argyris Dallis , Athanasios Balaskas , Sotirios Zarogiannis , Erasmia Rouka
Quantum mechanics (QM) is emerging as a powerful framework for studying disease-related mutations at the atomic and subatomic levels, providing mechanistic insights beyond those of classical models. In this review, we examined primary research to evaluate the extent to which QM is used to understand mutational mechanisms across various disease contexts. Our search was conducted in PubMed using the keywords “quantum mechanics” AND “mutations.” We also reviewed the reference lists of the retrieved articles for relevant data. All review articles were excluded. The final number of selected articles was thirty-four. These studies were categorized into two main modules: QM applications in non-communicable diseases and QM-based approaches to infectious diseases. In non-communicable diseases, especially cancer and neurodegeneration, QM simulations help clarify how mutations influence enzymatic catalysis, protein dynamics, and drug-target interactions, thereby improving our understanding of DNA repair, metabolic reprogramming, and resistance to targeted therapies. In communicable diseases, QM approaches can reveal how alterations in pathogens' genetic material impact protein–receptor interactions, virulence, and treatment effectiveness. Our findings highlight QM's role in shifting from discovery to therapeutics and underscore its applications in biomedicine. These advances could speed up drug development and personalized medicine.
量子力学(QM)正在成为在原子和亚原子水平上研究疾病相关突变的强大框架,提供了超越经典模型的机制见解。在这篇综述中,我们检查了初步研究,以评估QM在多大程度上用于理解各种疾病背景下的突变机制。我们在PubMed上搜索的关键词是“量子力学”和“突变”。我们还查阅了检索文章的参考文献列表,以获取相关数据。所有综述文章均被排除。最终入选的文章数量为34篇。这些研究分为两个主要模块:质量管理在非传染性疾病中的应用和基于质量管理的传染病方法。在非传染性疾病,特别是癌症和神经退行性疾病中,QM模拟有助于阐明突变如何影响酶催化、蛋白质动力学和药物靶标相互作用,从而提高我们对DNA修复、代谢重编程和靶向治疗耐药性的理解。在传染病中,QM方法可以揭示病原体遗传物质的改变如何影响蛋白质-受体相互作用、毒力和治疗效果。我们的发现突出了QM在从发现到治疗的转变中的作用,并强调了它在生物医学中的应用。这些进步可能会加速药物开发和个性化医疗。
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引用次数: 0
Macromolecular crowding and protein aggregation: Friend, foe or contextual force? 大分子聚集与蛋白质聚集:是友,是敌,还是环境力?
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.pbiomolbio.2025.12.001
Isabella V. Gimón , Conner Sandefur , Santiago Schnell
Protein aggregation plays a dual role in cellular biology, enabling essential functions such as intracellular organization, signaling, and storage, while also contributing to pathological states associated with misfolding and toxicity. However, existing literature lacks an integrated framework for predicting when crowding will favor productive assembly versus drive pathological outcomes—a gap that has hindered both mechanistic understanding and therapeutic development. This review examines how macromolecular crowding—an intrinsic feature of the intracellular environment—shapes protein aggregation outcomes by modulating key physicochemical parameters: volume exclusion, electrostatic interactions, aggregate morphology, cytoplasmic viscosity, and liquid–liquid phase separation. We demonstrate that crowding acts not as a universal promoter or inhibitor of aggregation, but rather as a context-dependent modulator that amplifies latent vulnerabilities in proteins predisposed to misfolding while facilitating productive assembly in properly regulated systems. By analyzing the mechanistic continuum between functional and pathological aggregation, we provide a framework for interpreting how identical molecular forces yield divergent biological outcomes depending on protein properties, environmental conditions, and cellular regulation. This perspective clarifies how the intracellular milieu governs aggregation dynamics and identifies promising avenues for therapeutic intervention, including strategic modulation of crowding conditions to promote protective assemblies while suppressing toxic aggregates in misfolding-related diseases. We conclude by outlining future directions toward quantitative, predictive models that integrate molecular mechanism with physiological context, bridging the gap between in vitro biophysics and in vivo cellular function.
蛋白质聚集在细胞生物学中起着双重作用,实现细胞内组织、信号传导和储存等基本功能,同时也有助于与错误折叠和毒性相关的病理状态。然而,现有文献缺乏一个完整的框架来预测拥挤何时有利于生产组装而不是驱动病理结果,这一差距阻碍了机制理解和治疗发展。本文综述了大分子聚集-细胞内环境的固有特征-如何通过调节关键的物理化学参数(体积排斥,静电相互作用,聚集形态,细胞质粘度和液-液相分离)来影响蛋白质聚集结果。我们证明,拥挤不是聚合的普遍启动子或抑制剂,而是作为一种环境依赖的调节剂,它放大了倾向于错误折叠的蛋白质的潜在脆弱性,同时促进了适当调节系统中的生产组装。通过分析功能性和病理性聚集之间的机制连续性,我们提供了一个框架来解释相同的分子力如何根据蛋白质特性、环境条件和细胞调节产生不同的生物学结果。这一观点阐明了细胞内环境如何控制聚集动力学,并确定了治疗干预的有希望的途径,包括在错误折叠相关疾病中战略性地调节拥挤条件以促进保护性聚集,同时抑制毒性聚集。最后,我们概述了定量预测模型的未来发展方向,这些模型将分子机制与生理背景相结合,弥合了体外生物物理学和体内细胞功能之间的差距。
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引用次数: 0
Rewiring lipid Metabolism: The central role of CPT1 in metabolic dysfunction 脂质代谢重组:CPT1在代谢功能障碍中的核心作用。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-20 DOI: 10.1016/j.pbiomolbio.2025.11.002
Dan Ni , Yuxuan Liu , Xiaofang Lin , Manqing Luo , Chuanhuan Deng , Jing Li , Pengfei Liang , Zhenguo Liu , Bimei Jiang
Carnitine palmitoyltransferase 1 (CPT1) serves as a critical gatekeeper in mitochondrial fatty acid oxidation and plays a central role in systemic energy homeostasis. The CPT1 family comprises three isoforms—CPT1A, CPT1B, and CPT1C—which exhibit distinct tissue distributions and regulatory features, enabling specialized metabolic functions in the liver, heart, skeletal muscle, and brain. CPT1 activity is tightly controlled through multiple mechanisms, including inhibition by malonyl-CoA, epigenetic modifications, and protein–protein interactions, all of which coordinate nutrient sensing and energy adaptation. Dysregulation of CPT1 has been implicated in the development of various metabolic disorders, including obesity, metabolic (dysfunction)-associated fatty liver disease (MAFLD), diabetic cardiomyopathy, and metabolic syndrome. This review summarizes recent advances in understanding the regulatory landscape and pathological roles of CPT1 and further discusses emerging therapeutic strategies. While CPT1-targeted interventions hold promise, challenges such as isoform specificity, off-target effects, and tissue-selective delivery must be addressed to achieve precision metabolic modulation.
肉毒碱棕榈酰基转移酶1 (CPT1)在线粒体脂肪酸氧化中起着关键的看门人作用,在全身能量稳态中起着核心作用。CPT1家族包括三种亚型——cpt1a、CPT1B和cpt1c,它们表现出不同的组织分布和调节特征,在肝脏、心脏、骨骼肌和大脑中具有特殊的代谢功能。CPT1的活性受到多种机制的严格控制,包括丙二酰辅酶a的抑制、表观遗传修饰和蛋白质-蛋白质相互作用,所有这些机制都协调着营养感知和能量适应。CPT1的失调与各种代谢性疾病的发展有关,包括肥胖、代谢(功能障碍)相关的脂肪性肝病(MAFLD)、糖尿病性心肌病和代谢综合征。本文综述了近年来在了解CPT1的调控前景和病理作用方面的进展,并进一步讨论了新兴的治疗策略。虽然以cpt1为目标的干预措施有希望,但必须解决诸如异构体特异性、脱靶效应和组织选择性递送等挑战,以实现精确的代谢调节。
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引用次数: 0
Advances in nanomaterials-assisted drug delivery, diagnosis, and action towards drug-resistant Mycobacterium 纳米材料辅助药物递送、诊断和对耐药分枝杆菌的作用的进展。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.pbiomolbio.2025.11.001
Parikshana Mathur , Pinky Choudhary , Rajkuberan Chandrasekaran , Ragini Singh , Hemant Kumar Daima
Threatening impact of tuberculosis (TB) on public health remains significant even after the global initiatives and emergence of multi-drug resistance (MDR) strains have made the situation complicated. Herein, the exploitation of the same medications for several decades, ineffective drug administration, and insufficient patient follow-up are some of the variables that have fuelled the resistance. As a result, the twenty-first century has seen the greatest number of multi-drug resistance TB cases. Nevertheless, nanotechnology has emerged as a promising tool against drug-resistant Mycobacterium tuberculosis, the bacterium responsible for TB. This seminal review highlights the most important findings from nanomaterials-related research to detect and counter TB. First, a deeper understanding of the essential molecular mechanisms underlying drug-resistance and drug-tolerance in Mycobacterium pathogen is provided along with biofilm formation and intracellular survival mechanisms. It is followed by detailed discussions about innovative nanomaterials-based drug delivery for antituberculosis medications, and different types of nanomaterials for direct antimicrobial actions. Then, nanotechnology-assisted diagnosis techniques and anti-biofilm possibilities for drug-resistant M. tuberculosis are elaborated. Finally, the challenges and perspectives related to nanomaterials-based theranostic for TB drug-resistance and treatment are provided with concluding remarks.
即使在全球行动和耐多药菌株的出现使情况变得复杂之后,结核病对公共卫生的威胁性影响仍然很大。在这里,几十年来使用相同的药物,无效的药物管理,以及患者随访不足是助长耐药性的一些变量。因此,21世纪出现了最多的耐多药结核病病例。然而,纳米技术已经成为对抗耐药结核分枝杆菌的一种很有前途的工具。结核分枝杆菌是导致结核病的细菌。这篇开创性的综述强调了纳米材料相关研究在检测和防治结核病方面的最重要发现。首先,更深入地了解分枝杆菌病原体耐药和耐药的基本分子机制以及生物膜形成和细胞内生存机制。随后详细讨论了基于创新纳米材料的抗结核药物递送,以及用于直接抗菌作用的不同类型纳米材料。然后,纳米技术辅助诊断技术和耐药结核分枝杆菌抗生物膜的可能性进行了阐述。最后,总结了基于纳米材料的结核病耐药治疗方法面临的挑战和前景。
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引用次数: 0
The DOPA scaffold: Tracing catechol chemistry from prebiotic earth to cognitive agency 多巴支架:从益生元地球到认知代理追踪儿茶酚化学。
IF 4.5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.pbiomolbio.2025.10.004
Amal Alachkar
L-3,4-dihydroxyphenylalanine (DOPA) is primarily defined by its role as the precursor to catecholamine neurotransmitters, a view substantiated by its status as the gold-standard treatment for Parkinson's disease. This framing obscures its profound evolutionary significance. This review reframes DOPA as a fundamental physicochemical scaffold whose core aromatic catechol-based properties: electron transfer, metal chelation, self-assembly, and polymerization into semiconducting biopolymers have been repeatedly repurposed throughout three billion years, from prebiotic Earth to the human brain.
From its plausible origins in prebiotic catalysis, these properties were leveraged by life to solve recurring challenges in survival and protection (e.g., microbial siderophores, protective melanins), settlement and colonization (e.g., marine bioadhesives), and competitive/cooperative communication (e.g., allelochemicals, social signaling). This evolutionary history of DOPA reveals a consistent pattern, a conserved 'Stress-Motion-Motivation-Action’ arc that links environmental challenges to the emergence of goal-directed behavior. I propose that DOPA's same ancient chemical logic was not discarded but repurposed in the mammalian brain. Beyond serving as a dopamine precursor, DOPA's non-canonical functions: adhesion, chelation, and polymerization into the semiconducting biopolymer neuromelanin, form a multiscale biophysical scaffold. This scaffold provides the structural and electrochemical stability necessary for the neural circuits and for the canonical dopamine signaling to execute not only motivation and movement but also the agency-related complex computations. This model thus bridges molecular biophysics with higher-order cognition, reframing DOPA as a fundamental material substrate for cognitive agency.
l -3,4-二羟基苯丙氨酸(DOPA)主要被定义为儿茶酚胺神经递质的前体,这一观点被其作为帕金森病的金标准治疗所证实。这种框架掩盖了其深刻的进化意义。这篇综述将DOPA重新定义为一种基本的物理化学支架,其核心的芳香儿茶酚性质:电子转移、金属螯合、自组装和聚合成半导体生物聚合物,在30亿年的时间里,从益生元地球到人类大脑,被反复地重新利用。从其可能的益生元催化起源来看,这些特性被生命利用来解决生存和保护(例如微生物铁载体,保护性黑色素),定居和定植(例如海洋生物粘合剂)以及竞争/合作通信(例如化感化学物质,社会信号)中反复出现的挑战。DOPA的进化史揭示了一个一致的模式,一个保守的“压力-运动-动机-行动”弧线,将环境挑战与目标导向行为的出现联系起来。我认为多巴同样古老的化学逻辑并没有被丢弃,而是在哺乳动物的大脑中被重新利用。除了作为多巴胺前体,多巴的非规范功能:粘附、螯合和聚合成半导体生物聚合物神经黑色素,形成了一个多尺度的生物物理支架。这种支架为神经回路和规范的多巴胺信号提供了必要的结构和电化学稳定性,不仅可以执行动机和运动,还可以执行与代理相关的复杂计算。因此,该模型将分子生物物理学与高阶认知联系起来,将多巴重构为认知代理的基本物质基质。
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