Heart rate variability (HRV) refers to small variations in consecutive normal cardiac cycles and is an important indicator of autonomic regulation. Although the frequency domain indices of HRV, such as low frequency (LF), high frequency (HF) and LF/HF, have been widely used to assess the activity of the sympathetic and parasympathetic nervous systems and their mutual regulation, their validity as indicators of autonomic nervous system function has been questioned. This study analyses the different views on the significance of LF, HF and LF/HF and examines their validity and effectiveness as indicators of autonomic nervous system function. In this study, it is proposed that LF, while influenced by sympathetic nerve activity, is not recommended for use alone to reflect sympathetic nerve activity, as it is also affected by other factors such as vagal nerve activity. HF, primarily controlled by cardiac vagal nerves, accurately reflects parasympathetic nervous system activity. LF/HF can reflect the regulatory role of the autonomic nervous system to a certain extent, but due to the non-linear relationship and the influence of other factors, the index of LF/HF is not precise.

The intricate interactions among the nervous system, endocrine system, and immune system constitute a sophisticated network. Neuroimmunology is an emerging interdisciplinary field that delves into the structure and function of the neuro-endocrine-immune regulatory network at the molecular, cellular, tissue, organ, and whole-body levels. Neuroimmune interactions persist throughout the entire lifespan, the dysregulation of which can lead to the onset and development of multiple diseases. In recent years, significant breakthroughs have been made in China in the frontier of the neuro-endocrine-immune-metabolism interdisciplinary field, with a primary focus on the regulation of the central nervous system. On one hand, novel mechanisms concerning the neural control of peripheral system functions have been revealed. The "brainspleen" axis was identified for the first time, shedding light on how emotions modulate immunity via the central nervous system. Additionally, mechanisms through which neurotrophic factors secreted by neurons regulate the immune function of the spleen have been elucidated. Moreover, neurological mechanisms underlying the anti-inflammatory effects of acupuncture therapy in traditional Chinese medicine have been clarified, detailing how stimulation of the Zusanli acupoint regulates immune function through specific neural populations. On the other hand, breakthroughs have been achieved concerning how peripheral organs regulate neural function, including investigations into the role of the "gut-brain" axis in processes such as animal vomiting and lightcontrolled blood glucose metabolism. These accomplishments have strengthened China's research foundation, propelling further exploration in the neuro-endocrine-immune-metabolism interdisciplinary field. This article spotlights recent advances in basic research of neuroimmunology conducted by domestic scientists, summarizing significant achievements and key scientific issues in five aspects: "basic units of neuro-immune interactions", "systemic physiological neuro-endocrine- immune regulation", "neuro-immune interactions and diseases", "physiological and pathological functions of glymphatic system", and "technical approaches and methodologies in neuroimmune interaction research".

Lactic acid is a decomposed product of anaerobic oxidation of glucose. Recent studies have shown that lactic acid is an important energy substance, signaling molecule, and immunomodulatory molecule, playing a significant role in cellular physiological and pathological processes. In vivo, both histone and non-histone proteins can undergo lactylation modification, thereby participating in the regulation of gene transcription, induction of macrophage polarization, and other processes. The discovery of protein lactylation modification has provided new directions for research on tumors and inflammation. Given the increasing attention paid to lactylation in the study of disease pathogenesis, this article summarizes the research progress of histone and nonhistone lactylation modification, and expound the key roles of lactylation modification in inflammation, cancer, cardiovascular and cerebrovascular diseases, as well as neurodegenerative diseases.

Adipose tissue is an important metabolic and endocrine organ, distributed in the subcutaneous tissue and around internal organs. Based on its morphological and functional characteristics, adipose tissue can be divided into white, brown and beige adipose tissue, which plays a key role in regulating glucose and lipid metabolism, as well as insulin sensitivity, and affects energy homeostasis. Sympathetic and sensory nerve fibers are distributed in adipose tissue. By releasing norepinephrine (NE), sympathetic nerves can promote lipolysis in white adipocytes and thermogenesis in brown adipocytes. The sympathetic regulation of adipose tissue is modulated by different stromal cells and immune cells within adipose tissue. Simultaneously, sensory nerves transmit signals from adipose tissue to the central nervous system. Disorders of neural innervation in adipose tissue usually lead to a series of health problems, such as obesity, diabetes, cardiovascular diseases, and cerebrovascular diseases.

Short-chain fatty acids (SCFAs) are produced by the gut microbiota through the fermentation of dietary fibers, which include acetic acid, propionic acid, and butyric acid. These SCFAs regulate various physiological functions in the body, such as immune, metabolic, and neurological functions, and are considered key factors affecting host health. SCFAs contribute to promoting lactate metabolism, increasing glycogen storage, and improving intestinal barrier function, thereby enhancing exercise performance. However, different types of SCFAs exhibit variations in their mechanisms of action and effects. This review discusses how SCFAs synthesized by the gut microbiota influence exercise performance and the underlying mechanisms, providing new insights and directions for the use of SCFAs derived from the gut microbiota to improve exercise performance.

Mechanotransduction occurs when tissues or cells are stimulated by external mechanical forces, initiating a series of signaling processes, with mechanosensitive ion channels playing a pivotal role in this signaling cascade. Among these channels, Piezo1 has been widely studied. Piezo1 has been found in a variety of mammalian tissues and can affect multiple signaling pathways after mechanical stimulation, involving processes such as vasodilation, cell migration, and inflammatory response. To explore the potential therapeutic value of Piezo1 and improve the understanding of its function, this article reviews literature on Piezo1 and summarizes the latest research progress on Piezo1 in the cardiovascular system, locomotor system, nervous system, respiratory system, digestive system, and reproductive system.

Gut is an important organ for communication between the organism and the external environment. It collects nutrients and removes waste, contributing significantly to maintaining the body's homeostasis and physiological functions. The gut contains various cell types and neural signaling molecules. Previous studies have indicated that specific receptors on the intestinal cells are activated by food, allowing for the perception of taste and nutritional components and conveying this information directly or indirectly to the brain. Intestinal perception is ubiquitous in many organisms in nature and conserved among species. Therefore, investigations into intestinal perception have critical implications for understanding the evolution of species and the adaptive mechanisms of organisms in nature. This review aims to provide a brief overview of current research on the molecular and circuit mechanisms underlying the perception of various substances in the gastrointestinal tract, which provides a theoretical basis for future investigations into the roles of the gut-brain axis in the adaptive evolution of individual organisms and the evolution of facilitation in organism-environment symbiosis.

IL-15 is a key molecule in immune regulation and is secreted by myeloid cells. IL-15 plays an important role in the homeostasis and function of T cells, natural killer (NK) cells, and memory CD8+ T cells. Due to its characteristics of wide expression and strict secretion, IL-15 holds significant therapeutic potential in various immune-related diseases. After IL-15 specifically binds to IL-15 receptor, it activates a variety of signaling pathways such as JAK/STAT, Ras/Raf/MAPK and PI3K/AKT, inducing cell proliferation, differentiation and apoptosis, thus exerting biological effects such as anti-tumor and anti-infection effects. This article reviews the role and associated mechanisms of IL-15 in diseases such as tumors, autoimmune diseases, cardiovascular diseases, and neuropsychiatric diseases, and summarizes the small molecule agonists and antagonists with IL-15 as potential therapeutic targets, aiming to provide a scientific basis for further investigation of the pathogenesis and drug research of IL-15 in immune system diseases and neuropsychiatric diseases.

Chronic pain and depression are two common diseases that endanger human health. They often co-occur and mutually influence each other, greatly increasing the difficulty of treatment. The occurrence of chronic pain and depression involves common or interacting neural circuits and neurotransmitter systems. Neuroinflammation also plays an important role in the pathogenesis of chronic pain and depression. Dysfunction in related neural circuitry and neuroinflammation are important mechanisms underlying the comorbidity between chronic pain and depression. Chronic stress is a critical cause of inducing depression and chronic pain. Previous studies have shown that dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the pathological basis for chronic stress-induced depression and comorbid pain. Chronic stress may promote neuroinflammatory response and dysfunction of neural circuits through HPA axis dysfunction, leading to the comorbidity of chronic pain and depression. This review discusses the pathogenesis of chronic stress-induced pain comorbid with depression, and elaborates on the pathogenesis of chronic stress-induced comorbidity of chronic pain and depression from the aspects of the HPA axis function, neuroinflammation, brain structure and neural circuits involved.

Programmed death protein-1 (PD-1) and its ligand, PD-L1, are critical immune checkpoints in tumors whose interaction negatively regulates the activation and proliferation of effector T cells, playing a crucial role in tumor cells evading immune surveillance. Blocking the binding of PD-1 to PD-L1 can relieve the inhibition of T cells by tumor cells or antigen-presenting cells, restoring their recognition and cytotoxicity against tumor cells. However, the expression of PD-L1 is intricately regulated and varies among different types of tumors, primarily occurring at genetic, transcriptional, and post-transcriptional levels. In this article, we review the regulatory processes involved in PD-L1 expression and its roles in tumor immunotherapy, which are of great significance in oncotherapy, as the focus of future research lies in achieving precise immunotherapy targeting tumors with distinct characteristics, guided by the regulatory mechanisms.

The visceromotor reflex is an important component of autonomic nervous system regulation, controlling the autonomous movements of many visceral organs, including the gastrointestinal tract, bladder, and cardiovascular system. The reflex movements of these organs are controlled by both the sympathetic and parasympathetic nervous systems to maintain their normal functions. In different states, the sympathetic/parasympathetic nervous systems are regulated accordingly to adapt to different physiological and environmental demands. When there are problems with the regulation of the autonomic reflex loop that governs the viscera, it may lead to various related diseases, seriously affecting physical and mental health. Therefore, a comprehensive understanding of the structure, function, and regulation of the visceromotor reflexes is of great significance for scientific research and clinical treatment.

Bone remodeling is an important process for maintaining bone homeostasis, and it is commonly believed that bone remodeling is mainly regulated by endocrine hormones. In recent years, there has been increasing evidence suggesting that the central nervous system is directly involved in regulating bone homeostasis through efferent nerves. Although it has been demonstrated that there are clear neural connections between the brain and skeletal tissues, the role of these neural connections in the brain's regulation of bone homeostasis is not well understood. In this paper, we will present recent advances in the field of brain regulation of bone metabolism, focusing on the neural connections between bone and brain, the regulation of bone homeostasis by the central nervous system and neural circuit, the regulation of bone homeostasis by the autonomic nervous system and sensory nervous system, respectively.

Stress can be found almost anywhere. Perceiving stress and regulating bodily functions to respond to danger constitute crucial mechanisms on which individuals rely for their survival. However, excessive or chronic stress can lead to the development of anxiety, posing a threat to individuals’ health. In recent years, many studies have indicated that stress and anxiety can promote the initiation and progression of cancer. These effects are primarily operated through the activation of the sympathetic nervous system, resulting in the release of relevant hormones or peripheral neurotransmitters. This process triggers the promotion of cell proliferation, survival, and angiogenesis by activating the relevant receptors on both tumor cells and the microenvironment. Consequently, it accelerates cancer progression. Simultaneously, it compromises the body 's immune response, enabling tumor cells to evade immune surveillance. Nonetheless, the precise mechanisms underlying how the neural circuits associated with stress perception and anxiety response are interconnected with tumors and influence the occurrence and development of tumors through the sympathetic nervous system remain unclear. This article surveys a comprehensive overview and summary of the connections between anxiety-related neural systems and the sympathetic nervous system, as well as the pathways through which the sympathetic nervous system affects tumors, laying the theoretical foundation for future cancer treatments.

Ischemic stroke is a leading cause of death and disability worldwide, with a complex pathogenesis and limited therapeutic options. In recent years, nano-drug delivery systems (NDDS) have shown great potential in the treatment of brain diseases. Nanocarriers can transport drugs across the blood-brain barrier and target diseased cells through the modification of targeting ligands. This article reviews the pathogenesis of ischemic stroke and the limitations of current therapeutic approaches, focusing on the progress of nano-drug delivery systems in the treatment of ischemic stroke. The challenges and future directions in this field are proposed, aiming to advance the development of nanomedicine delivery systems for the treatment of ischemic stroke.

With the rapid development of tumor chemotherapy, the overall survival of tumor patients has been continuously prolonged. However, the cardiovascular toxic side effects caused by chemotherapy seriously limit the effectiveness of tumor treatment, and have become a high-risk factor affecting the quality of life and survival rate of patients. Among them, chemotherapy-related vascular endothelial injury can disrupt vascular homeostasis, which serves as the pathological basis of cardiovascular toxic side effects such as acute vascular events (vasospasm, acute myocardial infarction, stroke, etc.), atherosclerosis, hypertension, and aneurysms. Exploring the mechanisms and protective strategies of chemotherapy-related vascular endothelial injury is of great clinical significance. This review aims to summarize the latest progress in the mechanisms of chemotherapy-associated vascular endothelial injury and related protective strategies.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, the pathogenesis of which remains unclear. Recent studies have shown that the gut microbiota can affect the host’ s cognition and behavior by affecting central nervous system function, making it a potential therapeutic target for neurodegenerative diseases. Dysbiosis of the gut microbiota and disruption of the intestinal physiological barrier can induce peripheral inflammatory responses, which, through mediating the release of physiologically active substances such as neurotransmitters and microbiota secretions, can affect neurogenesis and neuronal signaling, resulting in inflammatory reactions in the central nervous system, synergistically promoting the neurodegenerative progression of AD pathology. Therefore, investigations into the possible mechanisms by which dysbiosis of the gut microbiota affects the pathology of AD may provide new perspectives for the prevention and alleviation of AD, offering new strategies for promoting healthy aging.

Exosomes are a subtype of extracellular vesicles derived from endosomes and released by membrane fusion and exocytosis. Exosome-mediated intercellular communication plays a critical role in multiple physiological and pathological processes. Due to their low immunogenicity and ability to mediate long-distance transport of bioactive substances, exosomes are considered ideal biological carriers for drugs. Engineered exosomes can improve the targeting of drug delivery, making research on exosome-based drug delivery exceedingly promising. However, some studies have indicated that exosomes can facilitate pathological processes in diseased organisms. For instance, exosomes secreted by tumor cells can "mislead" immune cells or establish a favorable microenvironment, thus promoting tumor proliferation and migration. In neurodegenerative diseases, exosomes exacerbate the disease by promoting inflammatory responses and the spread of pathogenic proteins. This article reviews the development and pathological propagation of neurodegenerative diseases mediated by exosomes carrying toxic pathogenic proteins , offering new insights into the occurrence and development of neurodegenerative diseases, as well as cautions and recommendations for exosome engineering and clinical applications.

Alzheimer's disease is a chronic neurodegenerative disease for which there is currently no effective pharmacological treatment. Exercise is considered to be an effective and harmless non-pharmacological intervention. There are various forms of exercise, which have varying effects on the improvement of Alzheimer's disease. Based on the diversity of exercise modalities, this article reviews the effects of aerobic exercise, resistance exercise, high-intensity interval training, and multimodal exercise on Alzheimer's disease, analyzes the differences and connections between these modalities, and explores the related mechanisms of different exercise modalities in improving Alzheimer's disease. Although the mechanisms by which different exercise modalities improve Alzheimer's disease vary, they all alleviate disease progression through the mediation of brain-derived neurotrophic factors. This article may provide a theoretical basis for determining the best exercise modality for patients with Alzheimer's disease.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80%~85% of all lung cancer cases. The early diagnosis of NSCLC presents challenges due to limited diagnostic methods and lack of effective biomarkers. Furthermore, surgical intervention in the advanced stages of NSCLC is difficult, and the recurrence rate is high. MicroRNA (miRNA) and long non-coding RNA (lncRNA) are two crucial types of gene expression regulatory molecules that are widely involved in various biological activities and closely associated with multiple diseases. Quantities of miRNAs and lncRNAs exhibit significant differential expression in NSCLC and play crucial regulatory roles in the occurrence and development of tumors, thereby holding potential as biomarkers for NSCLC. This article reviews the research progress on the regulatory roles of miRNAs and lncRNAs in the occurrence and development of NSCLC.

Aquaporins (AQPs) are a family of water channels predominantly expressed on cell membranes. They are widely distributed throughout the human body and play crucial roles in multiple biological processes, such as homeostasis maintenance. Additionally, AQPs are actively involved in the pathophysiological processes of neurological disorders. They are closely associated with fluid movement, cerebrospinal fluid circulation, energy metabolism, signal transduction, neurogenesis, neural regeneration, and the development and stabilization of the blood-brain barrier within the central nervous system (CNS), contributing to the onset and progression of various CNS diseases, including cerebral edema, Alzheimer's disease, neuromyelitis optica, intracranial hypertension, and Parkinson's disease. So far, multiple types of AQPs have been identified in the CNS, with research attention mainly devoted to AQP1, AQP4, and AQP9. The study of AQPs is instrumental in deepening our understanding of CNS and providing potential therapeutic targets for associated diseases. This article demonstrates the physiological distribution of AQPs in the CNS, their regulatory mechanisms, physiological functions, and their associations with CNS diseases, offering novel insights for relevant neuroscientific research.