Physiology (Bethesda, Md.)最新文献_第3页

Ancient DNA and Human Physiology. 古代DNA和人类生理学。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-06 DOI: 10.1152/physiol.00047.2025

Misheelt Bayarsaikhan, Michael James Boyle, Phoebe V Demers, Edward W Habeck, Joanna H Romeyer-Dherbey, Shahar Silverman, Diyendo Massilani

{"title":"Ancient DNA and Human Physiology.","authors":"Misheelt Bayarsaikhan, Michael James Boyle, Phoebe V Demers, Edward W Habeck, Joanna H Romeyer-Dherbey, Shahar Silverman, Diyendo Massilani","doi":"10.1152/physiol.00047.2025","DOIUrl":"10.1152/physiol.00047.2025","url":null,"abstract":"Ancient DNA (aDNA) enables the reconstruction of chronologically sampled genomes from ancient humans, animals, plants, pathogens, and microorganisms, as well as environmental DNA, providing a record of biological changes through time. Improvements in short and degraded DNA extraction methods and low-cost sequencing now enable the generation of broad, cross-regional datasets that expand evolutionary analyses from past population demography to biological mechanisms. By tracking temporal shifts of allele frequencies, integrating functional genomics resources (e.g., gene expression, chromatin structure variation), modeling population demography to separate selection from genetic drift, and aligning genetic changes with archaeological, cultural, and climatic data, aDNA has the potential to link sequence variation to physiological function within their temporal and environmental contexts. In this review, we summarize illustrative case studies from aDNA research spanning complex traits, dietary adaptations, and responses to pathogens and other environmental changes, showing how human biology has evolved under multiple selective pressures through time. These dated signals help triage experimental work and expose mechanisms that are rare or absent in living cohorts. Although some challenges remain, such as geographic and temporal sampling disparities, limitations in data resolution and variant detection, and genotype-phenotype uncertainties, rapid methodological progress and stronger ethical frameworks are expanding what can be inferred, making aDNA a promising tool for refining physiological pathways, their timing, and their drivers.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367950","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

Sex Differences and Oxidative Stress in Cardiovascular Disease. 心血管疾病中的性别差异和氧化应激。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-11-01 Epub Date: 2026-03-24 DOI: 10.1152/physiol.00039.2025

Delphine O Okoye, Elizabeth Aboagye, Sol Swenson, Sarah Ngugi, Kelly Shay, Benard O Ogola

{"title":"Sex Differences and Oxidative Stress in Cardiovascular Disease.","authors":"Delphine O Okoye, Elizabeth Aboagye, Sol Swenson, Sarah Ngugi, Kelly Shay, Benard O Ogola","doi":"10.1152/physiol.00039.2025","DOIUrl":"10.1152/physiol.00039.2025","url":null,"abstract":"Cardiovascular disease (CVD) accounts for over $300 billion in direct health care costs and is expected to rise over time, worsening the economic burden. To close the gap in CVD outcomes between men and women, sex-specific study designs and druggable targets are essential. Sex differences driven by sex hormones are well established in CVD, particularly the cardioprotective effects of testosterone in men and estradiol in women; however, the role of sex chromosomes, particularly X-linked genes, is not yet fully understood. Sexual dimorphism in CVD shows that women are protected compared to men, which diminishes with age. The low awareness and understanding of CVD risk in women contribute to delays in treatment. Oxidative stress is a key player in CVD. In this review, we briefly introduce reactive oxygen species (ROS) and sex chromosomes. Next, we examine X-linked escapee genes, which provide a unique perspective on sex differences in biology. Thereafter, we discuss the role of oxidative stress in CVD and risk factors, including hypertension and atherosclerosis, and identify knowledge gaps and potential research opportunities to address CVD disparity among women. In closing, we highlight the clinical trial outcomes in CVD and antioxidant treatments.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505882","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

Central Command During Exercise: Hierarchical Integration of Feedforward and Feedback Cardiovascular Control. 运动中的中央指挥：前馈与反馈心血管控制的层次整合。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-10-28 DOI: 10.1152/physiol.90017.2026

Marcela S Araújo, Masaki Mizuno, Bruno M Silva, Lauro C Vianna

{"title":"Central Command During Exercise: Hierarchical Integration of Feedforward and Feedback Cardiovascular Control.","authors":"Marcela S Araújo, Masaki Mizuno, Bruno M Silva, Lauro C Vianna","doi":"10.1152/physiol.90017.2026","DOIUrl":"https://doi.org/10.1152/physiol.90017.2026","url":null,"abstract":"Cardiovascular regulation during exercise has traditionally been explained by the interaction between central command, a feedforward neural mechanism originating in higher brain centers, and peripheral cardiovascular reflexes, particularly the exercise pressor reflex and arterial baroreflex. Although central command is widely recognized as initiating autonomic adjustments in proportion to perceived effort, accumulating evidence indicates that its role extends well beyond the generation of parallel autonomic drive. In this review, we synthesize experimental findings spanning spinal and brainstem neurophysiology to integrative studies in intact animals and humans, showing that descending signals associated with central command may access the neural circuitry involved in processing peripheral cardiovascular information and regulating autonomic output. Neurophysiological studies identify multiple sites of interaction, including inhibitory gating of group III/IV muscle afferent transmission within the spinal dorsal horn and modulation of barosensory processing within the nucleus of the solitary tract. At the integrative level, studies of the arterial baroreflex, exercise pressor reflex, and trigeminally mediated diving reflex further demonstrate that central command can selectively regulate reflex expression and modify interactions among competing autonomic inputs rather than summating with them. Together, these observations support a conceptual evolution of central command from a feedforward initiator to a hierarchical autonomic organizing system (CHAOS) that dynamically integrates central command with peripheral cardiovascular feedback according to behavioral context. This CHAOS framework provides a unifying physiological interpretation for findings traditionally considered within individual reflex systems and offers a broader perspective on cardiovascular regulation during exercise and other conditions imposing competing autonomic demands.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149291784","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

Cardiac α1A-Adrenergic Receptors: Adaptive Physiology to Therapeutic Targeting. 心脏α 1a -肾上腺素能受体：治疗靶向的适应性生理学。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-10-23 DOI: 10.1152/physiol.00029.2026

Raghu Sundaresan Nagalingam, Britney G Alcira, Dhiren Akkina, Logan G Kirkland, Brian C Jensen

引用次数: 0

From Benefit to Harm: Context-Dependent Responses to Dietary Interventions. 从有益到有害：饮食干预的情境依赖反应。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-10-20 DOI: 10.1152/physiol.00026.2026

Lingyan Zhou, Zihan Guo, Jiahui Xiao, Wei Du, Yingzhe Ding, Feixiang Bao, Xingguo Liu

{"title":"From Benefit to Harm: Context-Dependent Responses to Dietary Interventions.","authors":"Lingyan Zhou, Zihan Guo, Jiahui Xiao, Wei Du, Yingzhe Ding, Feixiang Bao, Xingguo Liu","doi":"10.1152/physiol.00026.2026","DOIUrl":"https://doi.org/10.1152/physiol.00026.2026","url":null,"abstract":"Diet is a major determinant of human health and disease, and dietary interventions have emerged as promising adjunctive strategies to preserve neuronal function, improve metabolic control, suppress tumor growth, and delay aging. However, accumulating evidence indicates that their effects are critically dependent on the underlying metabolic, genetic, and pathological context. Beyond conventional adverse effects of excessive dietary restriction, such as nutrient deficiencies, muscle loss, and impaired immunity, recent studies have revealed novel context-dependent adverse effects with new mechanisms. Our study demonstrated that glucose restriction (GR) selectively induces degeneration of neurons with mitochondrial DNA (mtDNA) depletion by disrupting calcium homeostasis at mitochondria-endoplasmic reticulum contact sites (MERCS), revealing that the vulnerability to GR is critically determined by the pre-existing mitochondrial state. Another study showed that extreme GR promotes lung tumor metastasis by reshaping the pulmonary premetastatic immune microenvironment through tumor-derived exosomal tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), challenging the conventional view that GR is uniformly anti-tumorigenic. Together, these findings highlight that the same dietary intervention can produce divergent or even opposing outcomes depending on biological context. Here, we review major dietary interventions, including calorie restriction (CR), fasting diet, ketogenic diet (KD), and GR,and extend a context-dependent framework in which their effects are shaped by mitochondrial integrity, hormonal milieu, tissue-specific metabolism, oncogenic alterations, and immune status. This review underscores the importance of patient stratification and biomarker-guided optimization for the safe and effective application of dietary interventions.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281078","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

Physiopathology of PMOS from a Neuroendocrine Perspective. 从神经内分泌角度看PMOS的生理病理。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-09-29 DOI: 10.1152/physiol.00034.2026

Ludovica Cotellessa, Silvia Bongiovanni, Paolo Giacobini

{"title":"Physiopathology of PMOS from a Neuroendocrine Perspective.","authors":"Ludovica Cotellessa, Silvia Bongiovanni, Paolo Giacobini","doi":"10.1152/physiol.00034.2026","DOIUrl":"https://doi.org/10.1152/physiol.00034.2026","url":null,"abstract":"Polyendocrine metabolic ovarian syndrome (PMOS) is the most common reproductive and cardiometabolic disorder in women of reproductive age. Once viewed as primarily an ovarian disease, it is now recognized as a neuroendocrine-metabolic disorder driven by dysregulation of the hypothalamic-pituitary-gonadal axis. A central feature of the syndrome is increased gonadotropin releasing hormone (GnRH) pulsatility, which drives excess luteinizing hormone (LH) secretion, disrupts the LH/follicle stimulating hormone (FSH) balance, and promotes ovarian androgen excess and anovulation. Hypothalamic Kisspeptin neurons, the principal regulators of GnRH pulse generation, show altered activity and impaired steroid feedback sensitivity. Anti-Müllerian hormone (AMH) has emerged as an ovary-to-brain signal that directly stimulates GnRH neurons and remodels the neuroendocrine interface, amplifying LH secretion and perpetuating reproductive dysfunction. Developmental programming, through interactions among genetic, environmental, and epigenetic factors, may durably alter the organization and function of hypothalamic circuits, predisposing to neuroendocrine dysfunction later in life. In parallel, metabolic dysfunction, including insulin resistance and adipose tissue dysfunction, can interact bidirectionally with reproductive and neuroendocrine pathways, reinforcing hyperandrogenism and perturbing both reproductive and energy homeostasis. This review summarizes current knowledge of the neuroendocrine mechanisms underlying PMOS and discusses emerging targeted therapies that may offer disease-modifying approaches for this prevalent and heterogeneous disorder.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083740","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

Cellular and molecular mechanisms of muscle spindle development and function. 肌纺锤体发育和功能的细胞和分子机制。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-09-02 DOI: 10.1152/physiol.00017.2026

Cyrrus M Espino, Theanne N Griffith

{"title":"Cellular and molecular mechanisms of muscle spindle development and function.","authors":"Cyrrus M Espino, Theanne N Griffith","doi":"10.1152/physiol.00017.2026","DOIUrl":"10.1152/physiol.00017.2026","url":null,"abstract":"An organism's external environment is dynamic and ever-changing. Survival depends on an animal's ability to engage with its surroundings through adaptive and purpose driven movement. Organisms that rely on such movement are endowed with an internal sensory system, known as proprioception, which enables the precise detection and awareness of the body and its limbs in space. The principal receptors that give rise to this system are known as \"proprioceptors\", a unique population of peripheral sensory neurons embedded within skeletal muscle and tendons, referred to as muscle spindles and Golgi tendon organs, respectively. Over the years, advancements in cellular, molecular, and electrophysiological techniques have provided fundamental insight into the signaling pathways that regulate proprioceptor development. These same approaches have also facilitated the discovery of the ionic and neuromodulator mechanisms that regulate proprioceptor activity. In more recent years, emerging evidence suggests that proprioceptive feedback may engage in non-cell autonomous regulation of other physiological systems, potentially expanding their role beyond detectors of movement and force. In this review, we will examine the cellular and molecular mechanisms that govern the development and function of muscle spindle afferents. Furthermore, we will highlight their emerging influence on neurological and musculoskeletal disease.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883393","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

Physiology in Perspective. 透视生理学。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-09-01 Epub Date: 2026-07-23 DOI: 10.1152/physiol.00036.2026

Amanda Heidt

引用次数: 0

Understanding the Diseased Atria. 了解患病心房。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-09-01 Epub Date: 2025-12-29 DOI: 10.1152/physiol.00040.2025

Dan Tong

引用次数: 0

Microglial Neurotransmitter Receptors in Health and Disease. 健康和疾病中的小胶质神经递质受体。

IF 10.3

Physiology (Bethesda, Md.) Pub Date : 2026-09-01 Epub Date: 2026-03-06 DOI: 10.1152/physiol.00030.2025

Qianqian Bi, Guo Cheng, Ningting Chen, Xin Zhou, Quan Zhou, Xiaoli Liu, Xiao Z Shen, Peng Shi

{"title":"Microglial Neurotransmitter Receptors in Health and Disease.","authors":"Qianqian Bi, Guo Cheng, Ningting Chen, Xin Zhou, Quan Zhou, Xiaoli Liu, Xiao Z Shen, Peng Shi","doi":"10.1152/physiol.00030.2025","DOIUrl":"10.1152/physiol.00030.2025","url":null,"abstract":"Microglia are the major resident immune cells in the central nervous system (CNS). They emerge at very early stages of brain development and subsequently expand and persist through self-renewal within the CNS. As a result, microglial behaviors are profoundly shaped by the CNS microenvironment, enabling them to meet the unique demands of neural tissue and to cope with CNS stresses. Neurotransmitters are the primary chemical messages that are conveyed between neurons; however, glia cells, including microglia, are now known to express a wide array of neurotransmitter receptors as well. This positions neurotransmitters as a fundamental mode of communication among most CNS cells. Despite this, the significance of neurotransmitter signaling in microglia biology and function remains elusive. Research studies have begun to unravel the repertoire of neurotransmitter receptors expressed by microglia, the signaling pathways they engage, and the consequences for brain physiology and pathology. These advances have raised new questions and marked the beginning of a new era in neuron-microglia research. In this review, we summarize the latest discoveries concerning neurotransmitter receptors in microglial biology and CNS diseases, and we also discuss future perspectives, including potential clinical applications.","PeriodicalId":520753,"journal":{"name":"Physiology (Bethesda, Md.)","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367980","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