Physiological reviews最新文献_第2页

Magnetosensation - the unsolved mystery. 磁感应——未解之谜。

IF 28.7 1区医学

Physiological reviews Pub Date : 2026-03-28 DOI: 10.1152/physrev.00032.2025

Billy Y K Lam, E Pascal Malkemper

引用次数: 0

Antibody-drug conjugate design and mechanisms of action for cancer treatment: state of the art and beyond. 用于癌症治疗的抗体-药物偶联物设计和作用机制：最新进展及展望。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-03-19 DOI: 10.1152/physrev.00039.2025

Anthony Cheung,Yi Liu,Alicia M Chenoweth,Hanieh Montaseri,Benjamina Esapa,Vijay Chudasama,James R Baker,David E Thurston,Sophia N Karagiannis

{"title":"Antibody-drug conjugate design and mechanisms of action for cancer treatment: state of the art and beyond.","authors":"Anthony Cheung,Yi Liu,Alicia M Chenoweth,Hanieh Montaseri,Benjamina Esapa,Vijay Chudasama,James R Baker,David E Thurston,Sophia N Karagiannis","doi":"10.1152/physrev.00039.2025","DOIUrl":"https://doi.org/10.1152/physrev.00039.2025","url":null,"abstract":"Antibody-drug conjugates (ADCs) are a leading area of targeted cancer therapeutics, typically combining a tumour-associated antigen-specific antibody conjugated to a toxic payload that targets key cellular mechanisms, such as mitosis and survival. The global ADC clinical trial landscape has been expanding significantly, with over 430 ADCs reaching early to late clinical studies in the past two decades, up from just 90 between 2004 and 2014. The US Food and Drug Administration (FDA) has so far approved 14 ADCs for use in clinical oncology. This growth is likely driven by significant advances in antibody technology and conjugation methods enabling more effective and precise delivery to cancer cells and more effective payloads that target vital cancer biology. Here, we review the ADCs that have reached clinical approval as well as current and emerging trends in ADC development, and we discuss these from multiple perspectives, including ADC mechanisms of action, emerging antigen targets, linker and conjugation chemistry, payloads, combination of ADC with checkpoint inhibitor immunotherapy and antibody Fc-engineering. We also consider how the field is evolving through the application of artificial intelligence (AI) and pathology-based biomarker discovery. Combined, innovative and emerging ADC design coupled with precision medicine and patient stratification strategies hold great promise to develop diverse and personalised cancer treatments with improved therapeutic indices, and to enhance tolerability compared to traditional chemotherapy and current established ADCs. This review aims to assist researchers in exploring the evolution, characteristics, and development trends in ADC design and to provide new directions for future research.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"9 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal ensembles in cortical function and disease. 皮层功能和疾病中的神经元群。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-03-06 DOI: 10.1152/physrev.00003.2025

Rafael Yuste

{"title":"Neuronal ensembles in cortical function and disease.","authors":"Rafael Yuste","doi":"10.1152/physrev.00003.2025","DOIUrl":"https://doi.org/10.1152/physrev.00003.2025","url":null,"abstract":"Neuronal ensembles, defined as groups of coactive neurons, are physiological modules of the cerebral cortex. Calcium imaging and optogenetics have enabled mapping and manipulating ensembles with single cell resolution in mouse visual cortex, providing evidence of their importance. Ensembles dominate cortical activity, are generated endogenously or by sensory stimulation. Ensembles are imprinted by activating neurons synchronously and can be reactivated by \"pattern completion\" trigger cells. Intrinsic excitability mediates ensemble coactivation and reactivation, while UP states shield ongoing ensembles from external inputs. Neurons can belong to different ensembles, forming a combinatorial system that encodes visual stimuli accurately and stably. Ensembles contain pyramidal neurons and interneurons and inhibited \"offsemble\" cells. Cross-inhibition makes ensembles orthogonal from one another, while astrocytic activation increases ensemble occurrence. Ensembles can last for weeks, providing a substrate for long-term information storage, and they capture the recent history of stimulus presentation, implementing short-term memory. Optogenetic manipulation of ensembles demonstrates that they are necessary and sufficient for visual discrimination and perceptual states. Ensembles are altered in mouse models of epilepsy, schizophrenia, Alzheimer's disease, autism spectrum disorders and medically-induced loss of consciousness. An ensemble model of the cortex is proposed in which ensembles are functional units that activate each other via trigger cells and silence non-desired ensembles by cross-inhibition. This generates a map of orthogonal attractor states, forming a computationally powerful memory and processing system. Ensembles are likely involved in many brain diseases, so manipulating them could offer avenues for new therapeutics.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"70 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fueling the Fire: Metabolic Dysfunction and Senescence as Drivers of Lung Aging and Disease. 火上浇油：代谢功能障碍和衰老是肺部衰老和疾病的驱动因素。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-03-06 DOI: 10.1152/physrev.00024.2025

Corrine R Kliment,Aditi U Gurkar,Nayra Cárdenes,Richard Ramonell,Toren Finkel,Melanie Königshoff

{"title":"Fueling the Fire: Metabolic Dysfunction and Senescence as Drivers of Lung Aging and Disease.","authors":"Corrine R Kliment,Aditi U Gurkar,Nayra Cárdenes,Richard Ramonell,Toren Finkel,Melanie Königshoff","doi":"10.1152/physrev.00024.2025","DOIUrl":"https://doi.org/10.1152/physrev.00024.2025","url":null,"abstract":"With a rapidly expanding human population at advanced ages and age as the main driver for chronic diseases, we face the challenge of understanding tissue aging and devising new therapeutic interventions. Cellular senescence is an important hallmark of all aging tissues and has emerged as a potential key driver of chronic lung diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and asthma. This comprehensive review recapitulates current knowledge of pathways and processes involved in cellular senescence with emphasis on the role of mitochondrial dysfunction and the \"4 Ms\" (morphology, mitophagy, metabolism, and metabolites). We review our current knowledge of healthy lung aging, discuss which pathomechanisms in chronic lung disease are characterized by senescence, and summarize current target therapeutics and their impact on lung disease. Within this exponentially growing field, we propose emerging concepts and current gaps in knowledge which need to be addressed to develop better opportunities for therapeutic strategies and future investigations.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"3 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epithelial plasma membrane transporters as drug targets 上皮质膜转运蛋白作为药物靶点

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-03-04 DOI: 10.1152/physrev.00045.2025

Alan S. Verkman

引用次数: 0

Molecular Systems, Human Non-Coding Sequence Variants, and Blood Pressure. 分子系统，人类非编码序列变异和血压。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-01-30 DOI: 10.1152/physrev.00029.2025

Qiongzi Qiu,Mingyu Liang

{"title":"Molecular Systems, Human Non-Coding Sequence Variants, and Blood Pressure.","authors":"Qiongzi Qiu,Mingyu Liang","doi":"10.1152/physrev.00029.2025","DOIUrl":"https://doi.org/10.1152/physrev.00029.2025","url":null,"abstract":"The human genome harbors millions of non-coding sequence variants. Genome-wide association studies (GWAS) have identified thousands of robust associations linking non-coding variants to human physiological traits and complex diseases. Integrative approaches, including expression quantitative trait locus mapping, epigenomic profiling, and precise genome editing in trait-relevant cell types, enable the identification of effector genes and underlying regulatory mechanisms, such as long-range chromatin interactions, that mediate the effects of non-coding variants. Investigations of blood pressure (BP)-associated non-coding sequence variants have uncovered previously unrecognized roles of genes in BP regulation, reinforced the human genetic relevance of established BP regulatory pathways, and elucidated specific regulatory mechanisms by which non-coding variants influence gene expression and BP. Studies of orthologous non-coding genomic regions in animal models corresponding to human genomic regions harboring BP-associated variants have demonstrated substantial effects on BP, suggesting that the phenotypic impact of non-coding sequence variants may be large within human subgroups. Continued expansion of functional studies of trait-associated non-coding sequence variants, together with advances in mapping molecular quantitative trait loci and epigenomic landscapes, will provide novel insights directly relevant to human biology and disease and essential for understanding humans as molecular systems.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"82 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reversal Theory as a Complementary Perspective on Moment-to-Moment Variations in Motivation for Physical Activity. 逆转理论作为体育活动动机时刻变化的补充视角。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-01-30 DOI: 10.1152/physrev.00030.2025

Fabien D Legrand,Joanne Hudson,Ryan Rhodes

引用次数: 0

Impact of e-cigarette vaping on the immune system across the body. 电子烟对全身免疫系统的影响。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-01-24 DOI: 10.1152/physrev.00011.2025

Jorge A Masso-Silva,Alexia Perryman,Sophia Karandashova,Avnee Jaya Kumar,Laura Barnes,Nikita Kasaraneni,Laura E Crotty Alexander

引用次数: 0

The Clinical Pathophysiology of Atrial Fibrillation - Outstanding Questions from Bedside to Bench and Back. 心房颤动的临床病理生理学——从床边到台前和背部的突出问题。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-01-16 DOI: 10.1152/physrev.00020.2025

Andreas A Boehmer,Sandro Ninni,Jordi Heijman,Dobromir Dobrev,Stanley Nattel

{"title":"The Clinical Pathophysiology of Atrial Fibrillation - Outstanding Questions from Bedside to Bench and Back.","authors":"Andreas A Boehmer,Sandro Ninni,Jordi Heijman,Dobromir Dobrev,Stanley Nattel","doi":"10.1152/physrev.00020.2025","DOIUrl":"https://doi.org/10.1152/physrev.00020.2025","url":null,"abstract":"Atrial fibrillation (AF) is a major public health problem, associated with increased risks of heart failure, stroke, dementia, and mortality. The treatment of AF involves multiple potential approaches, all of which presently have significant limitations. Over the past 20 years, tremendous advances have been made in understanding the pathophysiological determinants of AF. The present narrative review article aims to address selected issues that are highly relevant to clinically important questions in AF pathophysiology, by reviewing insights from both experimental observations and complementary clinical investigations. Issues that we address include: 1) Introduction and mechanistic concepts; 2) The mechanistic basis for the crucial role of the pulmonary veins in AF; 3) The progressive natural history of AF; 4) The nature and mechanisms of secondary AF; 5) AF and heart failure with reduced ejection fraction; 6) AF and heart failure with preserved ejection fraction; 7) AF burden- importance and mechanistic determinants; and 8) The clinical importance of better understanding AF pathophysiology, leveraging new physiological knowledge and technologies to improve AF prevention. We consider in detail changes in ion channel and transporter function, the importance of inflammatory signaling, and the contribution of changes in tissue structure and composition in the development of AF-promoting atrial cardiomyopathy. The developments in our understanding of AF pathophysiology have been enormous and have produced many new conceptual and therapeutic opportunities, along with a wide range of important new questions. To capitalize on these opportunities and address the new questions that have emerged will require substantial additional investigation.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"177 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potassium channels in vascular smooth muscle cells. 血管平滑肌细胞中的钾通道。

IF 33.6 1区医学

Physiological reviews Pub Date : 2026-01-12 DOI: 10.1152/physrev.00017.2025

Tessa A C Garrud,Daniel M Collier,Jonathan H Jaggar

{"title":"Potassium channels in vascular smooth muscle cells.","authors":"Tessa A C Garrud,Daniel M Collier,Jonathan H Jaggar","doi":"10.1152/physrev.00017.2025","DOIUrl":"https://doi.org/10.1152/physrev.00017.2025","url":null,"abstract":"Vascular smooth muscle cells express several types of potassium (K+) channel which control physiological functions including contractility, migration, proliferation, and differentiation. Five primary classes of K+ channel are present in vascular smooth muscle cells: large-conductance Ca2+-activated BK), voltage-dependent K+ (KV), inward rectifier K+ (Kir), adenosine triphosphate (ATP)-sensitive K+ KATP), and two-pore-domain (tandem pore domain) K+ (K2P) channels. Vascular smooth muscle cells express specific sub-members, splice variants, and auxiliary subunits of these five K+ channel classes to customize their properties. Expression patterns of K+ channels in smooth muscle cells can vary depending on vessel type, size, and anatomical origin. The expression, activity, trafficking, and surface abundance of K+ channels can be regulated by a wide variety of stimuli, including membrane voltage, ions, molecules, lipids, and proteins, including those generated by signal transduction pathways. K+ channel function can exhibit sexual dimorphism, change in conditions such as pregnancy aging, and alter in different diseases, including systemic and pulmonary hypertension, diabetes mellitus/metabolic syndrome, and brain disorders. Genetic mutations in genes which encode K+ channels are also associated with pathological alterations in vascular smooth muscle function. Here, provide a comprehensive summary of approximately 40 years of literature investigating the expression, regulation, function, and pathological modification of BK, KV, Kir, KATP, and K2P channels in vascular smooth muscle cells.","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"81 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0