Since the discovery of the mechanosensitive Piezo1 channel in 2010, there has been a significant amount of research conducted to explore its regulatory role in the physiology and pathology of various organ systems. Recently, a growing body of compelling evidence has emerged linking the activity of the mechanosensitive Piezo1 channel to health and disease of the central nervous system. However, the exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes the current research on the mechanosensitive Piezo1 channel and its implications for central nervous system mechanobiology, retrospects the results demonstrating the regulatory role of the mechanosensitive Piezo1 channel on various cell types within the central nervous system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, and brain endothelial cells. Furthermore, the review discusses the current understanding of the involvement of the Piezo1 channel in central nervous system disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, and glioma.

The metabolic network’s primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body’s metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

Lactate, as a pivotal metabolite generated by the body, has attracted considerable attention in numerous biological disciplines in recent years. In addition to its role in supplying energy, lactate also functions as a signaling molecule, with the capacity to mediate a diverse array of physiological effects. Within the central nervous system, lactate is involved in the regulation of critical physiological processes, including neurogenesis, synaptic plasticity, mitochondrial biogenesis, neuroinflammation, and cerebral angiogenesis. Furthermore, lactate has been implicated in the pathogenesis of several central nervous system diseases, such as Alzheimer’s disease, stroke, and spinal cord injury, among others. Physical exercise is recognized as a significant neuroprotective strategy; however, further research is required to elucidate the underlying biological mechanisms. In essence, the role of lactate as a metabolic-epigenetic core is gradually becoming a subject of increasing academic interest. The regulatory function of lactate is thought to involve its production (via lactate dehydrogenase), shuttle (via monocarboxylate transporters), sensing (via G protein-coupled receptor 81), and lactylation modifications, among others. This review synthesizes current evidence to elucidate the multifaceted roles of lactate in central nervous system physiology and pathology under exercise regulation, with a view to bridging the gap between molecular mechanisms and therapeutic potential, thereby paving the way for novel strategies in central nervous system disease intervention.

Lactate has evolved from a metabolic byproduct to a central regulator of skeletal homeostasis and disorders, integrating metabolic flux with epigenetic reprogramming. Within the skeletal system, it modulates the processes of osteogenesis, osteoclastogenesis, chondrogenesis, and matrix synthesis by regulating the physiological activities of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, chondrocytes, and intervertebral disc cells, thereby maintaining skeletal homeostasis. Dysregulated lactate signaling is increasingly recognized as a pivotal pathological mechanism in degenerative, inflammatory, and neoplastic skeletal disorders. The presence of pathogenic lactate flux has been shown to drive disease-specific mechanisms, including, in osteoporosis, it disrupts osteoblast-osteoclast coupling; in osteoarthritis, it amplifies chondrocyte inflammation and matrix degradation; in rheumatoid arthritis, excess lactate enhances fibroblast invasiveness; in intervertebral disc degeneration, lactate accumulation induces acidosis and cell death; and in malignancies, lactate simultaneously nourishes osteoclasts and suppresses anti-tumor immunity. Currently, emerging preclinical evidence indicates that therapeutic strategies targeting lactate metabolism, transport, receptor signaling, and lactylation show promise. However, challenges such as cell-type-specific effects, metabolic compensation, and systemic off-target risks persist. This review comprehensively examines the regulatory role and mechanisms of lactate in skeletal homeostasis and evaluates the therapeutic potential of lactate-based interventions for skeletal disorders. The advancement of lactate-based interventions is contingent on the development of bone-specific delivery systems and personalized approaches informed by metabolic-epigenetic profiles, offering promising new avenues for treating skeletal disorders.

Physical inactivity among adults is a major contributor to the escalating global burden of neurodegenerative diseases and mental disorders. The “Weekend Warrior” (WW) pattern—characterized by condensing the recommended volume of physical activity (PA) into one or two days—has emerged as a potential strategy for time-constrained adults. However, a systematic synthesis comparing the potential association of the WW pattern on neuropsychological outcomes (e.g., neurodegenerative diseases, mental health conditions and cognitive function) with those of inactive (IA) and regular exercise (RE) patterns remains limited. This systematic review aimed to assess the associations of the WW pattern with neurodegenerative diseases (e.g., dementia, Parkinson’s disease), mental health conditions (e.g., depression, anxiety, psychological distress), and cognitive function (CF), and to compare these neuropsychological outcomes with those associated with IA and RE patterns. A systematic search of PubMed, Web of Science, ScienceDirect, and Chinese databases (CNKI, Wanfang) was conducted for observational studies published from inception to October 2025. Thirteen studies (5 cohort and 8 cross-sectional studies) involving adults were included. The assessment of methodological quality was conducted using the Agency for Healthcare Research and Quality (AHRQ) methodology and the Newcastle–Ottawa Scale (NOS). The majority of included studies indicated that the WW pattern was inversely associated with the risks of neurodegenerative diseases and mental health conditions and enhanced CF, exhibiting associations of a similar magnitude to those of RE. Furthermore, the synthesis highlighted prevailing gaps in the extant literature, particularly regarding the lack of randomized controlled trials, insufficient control for confounding variables such as social context, and the limited investigation into the neurobiological mechanisms underlying these associations. This systematic review emphasizes the WW pattern as a viable and time-efficient strategy that promotes positive neuropsychological outcomes, exhibiting associations of a similar magnitude to those observed with RE. The findings substantiate the flexibility inherent in PA guidelines, underscoring that adhering to recommended PA volumes is highly beneficial, even when accumulated within a condensed timeframe. Future research should prioritize randomized controlled trials and investigations into neurobiological mechanisms to further validate causal relationships and elucidate the underlying mechanisms driving these associations.