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".

Endoplasmic reticulum (ER) is a crucial organelle involved in protein synthesis, folding, lipid metabolism, Ca2+ storage and the transport of nascent peptide chains. Disturbing ER homeostasis under stress can lead to endoplasmic reticulum stress (ERS), which maintains ER homeostasis and restores cell function by activating the unfolded protein response. Autophagy is generally considered a cellular survival mechanism, which can be initiated under stress conditions like starvation to remove damaged organelles, protein aggregates or provide energy for the cells. Studies have shown that ERS regulates autophagy, which induces cell survival or intervenes in the development of diseases under different circumstances. Therefore, this article reviews recent progress on the role and molecular mechanisms of ERS in autophagy regulation.

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.

Hypothyroidism is a common condition resulting from a deficiency in the thyroid hormone. While it can typically be effectively corrected with hormone replacement therapy, it may become fatal if left untreated. The thyroid hormone plays a crucial role in human growth, development, and functions of multiple organs. Clinical manifestations of hypothyroidism vary according to factors such as age and sex. Experimental animal models of hypothyroidism are widely used in preclinical studies of the pathophysiological mechanisms of hypothyroidism, as well as in the evaluation of treatment and prevention effects. Currently, effective models of hypothyroidism include surgical, dietary, pharmacological, genetic, radiological, and immunological methods. Each model has its own advantages and disadvantages based on different principles and can be selected according to the experimental purpose. In this article, we review recent studies on the animal models of hypothyroidism, discussing the modeling methods, as well as the advantages and disadvantages of each model, with the aim of selecting the optimal model for experiments.

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.

RNA splicing, a critical process in eukaryotic gene expression, plays a fundamental role in the regulation of gene expression by removing introns from precursor mRNA and joining exons. This process is primarily mediated by the spliceosome complex, while the assembly and activation of the spliceosome predominantly rely on splicing factors, facilitating the two-step transesterification. The splicing factor 3B subunit 1 (SF3B1) occupies a crucial position within the U2 RNP that constitutes the spliceosome complex. Alternations in the phosphorylation level of SF3B1 affect the cellular splicing process, subsequently influencing normal cell function, as well as the proliferation and migration of tumor cells. This article summarizes the research to date on SF3B1 within the context of phosphoproteomics, with particular emphasis on the role of SF3B1 in splicing and the impact of phosphorylation modifications on SF3B1.

Depression is a common and serious psychiatric disorder, the pathogenesis of which remains incompletely elucidated. Currently, there are several hypotheses about the pathogenesis of depression, and the latest evidence suggests that neuroinflammation is closely associated with the onset and development of depression. With the advancement of neuroscientific technology, the role of astrocytes in depression has been receiving increasing attention. Studies have shown that depression is associated with astrocyte-mediated neuroinflammation, in which microglia, the NF-κB signaling pathway, and NLRP inflammasomes are involved, providing potential targets for the treatment of depression. In this article, we review the research progress on astrocyte-mediated neuroinflammation associated with depression.

Osteoarthritis is a chronic degenerative joint disease that occurs mostly in the elderly and is one of the most common bone metabolic diseases, in which cells involved in the metabolic abnormalities mainly include chondrocytes. As an important cause of the abnormal metabolism of chondrocytes, mitochondrial dysfunction is closely associated with the occurrence and development of osteoarthritis. Mitophagy, the selective mitochondrial autophagy for damaged or dysfunctional mitochondria, plays an important role in the maintenance of mitochondrial quality control and mitochondria homeostasis. Accumulating evidence suggests that mitophagy plays a vital regulatory role in osteoarthritis, indicating that regulating the level of mitophagy may be a new strategy for its prevention and treatment. Therefore, we review the potential mechanism underlying the involvement of mitophagy in osteoarthritis, aiming to provide a theoretical basis for research related to mitophagy as a target for osteoarthritis treatment.

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.

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.

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.

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.

Claudin-10, a member of the claudin family of tight junction transmembrane proteins, is expressed in epithelial cells of multiple organs and tissues, with two isoforms, claudin-10a and claudin-10b. It plays a critical role in maintaining the selective permeability of cell membrane and regulating ion transport through the paracellular pathway. In recent years, claudin-10 has been reported to be associated with the development and progression of a variety of diseases. Diseases characterized by impaired function of multiple organs due to mutations in the claudin-10 gene are collectively referred to as HELIX syndrome, which generally results in clinical manifestations such as anhidrosis, renal disease, hypokalemia, xerostomia, and severe enamel wear. In this review, the research progress on claudin-10 will be presented, including its molecular structure, expression and distribution, as well as the relationship between claudin-10 function and diseases.

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.

Programmed cell death plays a critical role in maintaining organism growth and development, homeostasis and physiological functions of organs. Ferroptosis suppressor protein 1 (FSP1) is capable of regulating not only apoptosis but also ferroptosis, mainly dependent on its intracellular distribution, yet associated mechanisms still unclear. This review summarizes the role and regulatory mechanism of FSP1 in two types of programmed cell death, by which new strategies can be provided for the diagnosis and treatment of tumors, neurodegenerative diseases and other diseases related to programmed cell death via precisely regulating the expression and distribution of FSP1 in cells.

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.