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The Physiology behind the Epidemiology of Heat-Related Health Impacts. 热相关健康影响流行病学背后的生理学。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-07-02 DOI: 10.1152/physiol.00012.2025
Daniel Gagnon, Zachary J Schlader, Ollie Jay
{"title":"The Physiology behind the Epidemiology of Heat-Related Health Impacts.","authors":"Daniel Gagnon, Zachary J Schlader, Ollie Jay","doi":"10.1152/physiol.00012.2025","DOIUrl":"10.1152/physiol.00012.2025","url":null,"abstract":"<p><p>A direct consequence of climate change is the intensification of hot weather and extreme heat events that are epidemiologically associated with a greater risk of heat-related illnesses and other adverse health outcomes, often resulting in subsequent hospital admissions and mortality. The health risks associated with hot weather directly arise from the body's physiological responses (i.e., heat strain) to heat exposure. The magnitude of heat strain experienced and the extent of heat strain required to cause an adverse health outcome can be modulated by personal characteristics and the adoption of protective behaviors. This review presents the pathophysiological mechanisms responsible for the epidemiological association between heat exposure and a greater risk of heat illnesses (e.g., heat exhaustion, heatstroke), adverse cardiovascular events, and acute kidney injury or failure. These mechanisms are framed within the larger context that defines heat-related health risks, and we provide examples and perspectives of how physiologists are uniquely positioned to contribute to risk reduction and adaptation efforts to protect humans against the adverse health impacts of heat, while maintaining optimum well-being and performance.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Cells to Selves and Back: Human Neurodiversity at Single-Cell Resolution. 从细胞到自我再回来：单细胞分辨率下的人类神经多样性。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-06-18 DOI: 10.1152/physiol.00010.2025
Manuel Lessi, Nicolò Caporale, Giuseppe Testa
{"title":"From Cells to Selves and Back: Human Neurodiversity at Single-Cell Resolution.","authors":"Manuel Lessi, Nicolò Caporale, Giuseppe Testa","doi":"10.1152/physiol.00010.2025","DOIUrl":"10.1152/physiol.00010.2025","url":null,"abstract":"<p><p>Human brain development is characterized by a complex cellular and molecular landscape, which varies both within and between individuals. Here, we explore the transformative impact of single-cell omics technologies on our understanding of human neurodiversity and neurocomplexity. We trace historical progressions of cellular and molecular biology, highlighting the cell as a pivotal \"place holder\" for biological inquiry, as a basis to better understand the current revolution of single-cell profiling, enabling the study of individual genomes and environmental interactions at unprecedented resolution. Starting from the challenges of defining cell types and states within neurodevelopment, we emphasize the significance of moving beyond categorical distinctions to understand the molecular basis of interindividual neurodiversity, including genetics, environment, and developmental stochasticity. We introduce the concept of \"in vitro epidemiology,\" leveraging neural organoids and multiplexing approaches to model population-scale cohorts in vitro and thus enabling the dissection of gene-environment interactions at single-cell resolution. We further discuss technical advancements and computational methodologies that are driving the field forward, including the efforts to create comprehensive cell atlases of the human brain and the emerging challenges in data integration and analysis. Finally, we anticipate future perspectives for single-cell studies and neural organoids in advancing our understanding of neurobiology and cell-based strategies for drug discovery and personalized treatment.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain Capillary Ion Channels: Physiology and Channelopathies. 脑毛细血管离子通道：生理学和通道病变。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-08-01 DOI: 10.1152/physiol.00015.2025
Osama F Harraz, Ahmed M Hashad
{"title":"Brain Capillary Ion Channels: Physiology and Channelopathies.","authors":"Osama F Harraz, Ahmed M Hashad","doi":"10.1152/physiol.00015.2025","DOIUrl":"10.1152/physiol.00015.2025","url":null,"abstract":"<p><p>The brain relies on an intricate vascular network to deliver oxygen and nutrients through functional hyperemia, a process critical for matching blood flow to neuronal activity. This review explores the roles of ion channels in brain capillary endothelial cells and pericytes, focusing on their contributions to neurovascular coupling. Key endothelial ion channels, including Kir2.1, K<sub>ATP</sub>, transient receptor potential (TRP) vanilloid 4 (TRPV4), TRP ankyrin 1 (TRPA1), and Piezo1, regulate membrane potential and calcium dynamics, facilitating rapid electrical and chemical signaling that modulates blood flow. Pericytes, categorized as ensheathing and thin strand, express ion channels such as K<sub>ATP</sub>, voltage-gated calcium channels, canonical TRP channels (TRPCs), and TMEM16A, which govern contractility and orchestrate blood flow responses. Additionally, we discuss channelopathies in conditions like Alzheimer's disease, cerebral small vessel diseases, hypertension, and ischemic stroke, where ion channel dysfunction impairs brain blood flow regulation. Emerging evidence underscores the therapeutic potential of targeting capillary ion channels to restore neurovascular function in these disorders.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases. 生长激素和IGF-1在大脑和神经精神疾病中的作用。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-07-07 DOI: 10.1152/physiol.00009.2025
Manuel H Aguiar-Oliveira, Margaret C S Boguszewski, Diego L Rovaris, Jose Donato
{"title":"Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases.","authors":"Manuel H Aguiar-Oliveira, Margaret C S Boguszewski, Diego L Rovaris, Jose Donato","doi":"10.1152/physiol.00009.2025","DOIUrl":"10.1152/physiol.00009.2025","url":null,"abstract":"<p><p>Growth hormone (GH) is secreted by the anterior pituitary gland under the control of hypothalamic neuroendocrine neurons that express somatostatin or growth hormone-releasing hormone (GHRH). Ghrelin, originating primarily in the stomach, is also an important GH secretagogue. GH stimulates the hepatic secretion of insulin-like growth factor-1 (IGF-1) and the expression of IGF-1 in extrahepatic tissues, including the brain. Many regions of the brain express receptors for GH, IGF-1, and ghrelin. In recent decades, evidence from both human and animal studies has indicated that GH, IGF-1, and ghrelin regulate numerous brain functions. Alterations in the secretion or sensitivity to these hormones may represent risk factors for developing neurodegenerative diseases (e.g., Alzheimer's and Parkinson's) and neuropsychiatric conditions (such as depression, anxiety, posttraumatic stress disorder, schizophrenia, and bipolar disorder). Additionally, classical neurodevelopmental disorders such as autism spectrum and attention-deficit hyperactivity disorders may also be influenced by somatotropic hormones. This review aims to summarize and discuss the emerging role of GH and IGF-1 in influencing brain function and the predisposition to brain diseases and neuropsychiatric disorders.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
What Do We Know of Human Fuel Use during Aerobic Exercise, and How Do We Know It? 我们对有氧运动中人体的燃料消耗了解多少？我们是如何知道的？
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-08-05 DOI: 10.1152/physiol.00002.2025
Jessie Axsom, Zolt Arany
{"title":"What Do We Know of Human Fuel Use during Aerobic Exercise, and How Do We Know It?","authors":"Jessie Axsom, Zolt Arany","doi":"10.1152/physiol.00002.2025","DOIUrl":"10.1152/physiol.00002.2025","url":null,"abstract":"<p><p>Aerobic exercise is arguably the most metabolically demanding challenge imposed on the human body. The metabolic adaptations to exercise are complex, involving most tissues and differing substantially depending on the type, severity, and duration of exercise as well as the extent of prior training. Studies of these metabolic responses have been ongoing for decades, including the active National Institutes of Health (NIH)-supported consortium MotrPAC. Most studies have been carried out in model organisms, generally rodents or dogs. However, the metabolism of these model organisms substantially differs from humans. We therefore review here what is known specifically of human metabolism during exercise. For the sake of brevity, we focus on aerobic exercise without extensive prior training. We review methods used to reach conclusions, highlight the many remaining unknowns, and discuss questions requiring future experimental attention.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adipose Progenitor Cells in Thermogenesis and Metabolic Regulation. 脂肪祖细胞在产热和代谢调节中的作用。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2026-01-01 Epub Date: 2025-08-01 DOI: 10.1152/physiol.00006.2025
Cigdem Sahin, Yu-Hua Tseng
{"title":"Adipose Progenitor Cells in Thermogenesis and Metabolic Regulation.","authors":"Cigdem Sahin, Yu-Hua Tseng","doi":"10.1152/physiol.00006.2025","DOIUrl":"10.1152/physiol.00006.2025","url":null,"abstract":"<p><p>Thermogenic adipose tissues, including brown and beige, exhibit remarkable cellular and metabolic adaptations to environmental and physiological cues, contributing to improved metabolic health. Among these adaptations, adipose progenitor cells (APCs), a heterogeneous cell population comprising distinct subsets, play a crucial role in generating thermogenic adipocytes and promoting healthy adipose tissue remodeling and metabolic homeostasis. Therefore, targeting APCs offers a potential therapeutic approach for regulating adipose plasticity and remodeling to address metabolic dysregulation. The precise identity of APCs and the roles of specific APC subtypes in metabolic regulation and diseases remain to be elucidated. Here, we summarize recent findings on the lineage of APCs that give rise to thermogenic adipocytes and how environmental conditions regulate their proliferation and differentiation. Finally, we discuss the potential of targeting APCs as an alternative therapeutic strategy to combat metabolic diseases.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12385725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes. 1型糖尿病ß细胞功能障碍的分子和炎症病因。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2025-11-01 Epub Date: 2025-05-27 DOI: 10.1152/physiol.00008.2025
Cameron R Rostron, Carmella Evans-Molina
{"title":"Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.","authors":"Cameron R Rostron, Carmella Evans-Molina","doi":"10.1152/physiol.00008.2025","DOIUrl":"10.1152/physiol.00008.2025","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune-mediated destruction of pancreatic β-cells; however, recent findings indicate that intrinsic stress pathways within β-cells may contribute to the initiation or perpetuation of autoimmunity. Here, we discuss the molecular and inflammatory etiologies of β-cell dysfunction in T1D, with a focus on cytokine signaling, endoplasmic reticulum stress, mitochondrial dysfunction, and senescence.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structures and Molecular Mechanisms of Insect Odorant and Gustatory Receptors. 昆虫嗅觉和味觉受体的结构和分子机制。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2025-11-01 Epub Date: 2025-07-10 DOI: 10.1152/physiol.00011.2025
Xiangnan Zhang, Demin Ma, Jiangqin Wang, Nannan Su, Jiangtao Guo
{"title":"Structures and Molecular Mechanisms of Insect Odorant and Gustatory Receptors.","authors":"Xiangnan Zhang, Demin Ma, Jiangqin Wang, Nannan Su, Jiangtao Guo","doi":"10.1152/physiol.00011.2025","DOIUrl":"10.1152/physiol.00011.2025","url":null,"abstract":"<p><p>Insects rely on chemoreceptors in sensory neurons to detect and discriminate various chemicals in constantly changing environments. Among the chemoreceptors, odorant receptors (ORs) and gustatory receptors (GRs) play essential roles in sensing different odorant and tastant molecules, thereby regulating insects' physiology and behaviors such as feeding, mating, and alarming. ORs and GRs are evolutionarily related seven-transmembrane helical proteins that constitute a large family of tetrameric ion channels. In recent years, great progress has been made in the structures and molecular mechanisms of insect ORs and GRs. In this review, we summarize the available structures of insect ORs and GRs, analyze their diverse ligand recognition modes, and examine their conserved ligand activation mechanisms. These structural analyses will not only enhance our understanding of the molecular basis of insect ORs and GRs but also provide critical insights for the future discovery of repellents and attractants.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physiology in Perspective. 生理学透视- 2025年9月。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2025-11-01 Epub Date: 2025-09-12 DOI: 10.1152/physiol.00031.2025
Nikki Forrester
{"title":"Physiology in Perspective.","authors":"Nikki Forrester","doi":"10.1152/physiol.00031.2025","DOIUrl":"10.1152/physiol.00031.2025","url":null,"abstract":"","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"486"},"PeriodicalIF":10.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Immunopathophysiology of Organ Fibrosis: from Mechanisms to Immunotherapies. 器官纤维化的免疫病理生理学：从机制到免疫治疗。
IF 10.3
Physiology (Bethesda, Md.) Pub Date : 2025-11-01 Epub Date: 2025-05-27 DOI: 10.1152/physiol.00063.2024
Jingyi He, Irina Ferapontova, Jing Chen, Masamichi Ito, Takayuki Isagawa, Norihiko Takeda, Christian Stockmann
{"title":"The Immunopathophysiology of Organ Fibrosis: from Mechanisms to Immunotherapies.","authors":"Jingyi He, Irina Ferapontova, Jing Chen, Masamichi Ito, Takayuki Isagawa, Norihiko Takeda, Christian Stockmann","doi":"10.1152/physiol.00063.2024","DOIUrl":"10.1152/physiol.00063.2024","url":null,"abstract":"<p><p>Fibrosis is the ultimate outcome of various chronic diseases that affect multiple organs, including the liver, lungs, heart, and kidneys. This pathological process is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts in response to chronic injury, as part of a degenerative process of dysregulated tissue repair. Although numerous pathways have been implicated in the development of fibrosis, the precise mechanisms that drive and exacerbate organ fibrosis remain inconclusive. Consequently, there are currently very limited treatments for organ fibrosis. In recent years, immune cells have been identified as critical mediators of the fibrotic cascade, capable of inducing tissue damage or promoting repair. Harnessing immune cells and immunotherapeutic approaches to intervene in the fibrotic process is a promising avenue toward new treatment options. In this review, we explore the pathophysiology of fibrosis in various organs, with a specific focus on the role of immune cells in both the development and regression of fibrosis as well as the latest preclinical findings in relation to immunotherapeutic treatment approaches. Understanding the role of immune responses in fibrotic diseases will aid in the development of immunotherapeutic strategies that target key profibrotic cytokines and immune cells, with the aim of preventing fibrosis or promoting its regression.</p>","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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