Lactate is a key product of glycolysis. While historically dismissed as a metabolic waste, lactate has been recognized to play a crucial role as an energy source, a signaling molecule, and a key regulator in various biological processes. Notably, lactate can induce lactylation, a posttranslational modification in which lactate-derived lactoyl groups covalently bind to lysine residues of target proteins. Recent studies have demonstrated that lactylation plays a critical role in cellular metabolism, differentiation, proliferation, immune regulation, and tumor initiation and progression. Particularly, the mechanisms by which lactylation regulates cell differentiation have been a prominent focus of current research. In this review, we illustrate the significant role of lactate-induced lactylation in regulating the differentiation of embryonic stem cells, myoblasts, and osteoblasts, aiming to provide a novel perspective on lactate and lactylation, and to identify potential targets for clinical investigation of diseases associated with dysregulated cell differentiation.

Synapses are the fundamental units of the central nervous system (CNS), and their structural and functional integrity underpins brain activity. Synaptic loss and dysfunction are central to the pathogenesis of multiple neurological disorders. As a key receptor widely expressed in the CNS, metabotropic glutamate receptor 5 (mGluR5) plays a critical role in regulating synaptic structure and function. This review summarizes the structure and distribution of mGluR5, its role in regulating synaptic plasticity under physiological conditions, and how aberrant mGluR5 signaling drives synaptic deficits and disease progression under pathological conditions, aiming to provide a theoretical foundation for developing mGluR5-targeted therapies for neurological disorders.

Cervical cancer poses a serious threat to women's health, with an immunosuppressive tumor microenvironment being a major obstacle to effective immunotherapy. Recently, lactate, a cornerstone of tumor metabolic reprogramming, has garnered considerable interest for its role in fostering this immunosuppressive tumor microenvironment in cervical cancer. Lactate not only compromises immune cell function by establishing a metabolic barrier and sequestering critical nutrients such as glucose but also directly acidifies the microenvironment, thereby systematically inhibiting the anti-tumor activity of immune cells, including T cells. Concurrently, lactate regulates immune cell function through the activation of specific receptor mediated signaling pathways, such as G protein-coupled receptor 81, and further sculpts the immunosuppressive milieu via the epigenetic mechanism of lactylation modification. Moreover, lactate engages in a synergistic network with key signaling molecules, including programmed death-ligand 1 and transforming growth factor-beta, to collectively drive immune escape. This review aims to systematically elucidate the sources, metabolic features, and multidimensional immunosuppressive mechanisms of lactate in the cervical cancer immune microenvironment, providing a rationale for developing novel therapeutic strategies that target the lactate pathway.

Glucocorticoid-induced osteoporosis (GIOP) ranks as the leading cause of secondary osteoporosis, with a complex pathogenesis. Recent studies have revealed that osteocytes serve as the primary regulators of skeletal homeostasis and bone remodeling. Metabolic reprogramming refers to the process by which cells alter their metabolic patterns to meet their material and energy requirements, primarily involving the regulation of pathways such as carbohydrate metabolism, lipid metabolism, and amino acid metabolism. This review focuses on osteocyte bioenergetics, and elucidates the mechanisms by which glucocorticoid-driven metabolic reprogramming in osteocytes contributes to the onset and progress of GIOP. It aims to provide new insights into the mechanisms of GIOP and its clinical treatment from the perspective of energy metabolism.

Nucleolar stress is a cellular stress response caused by various internal and external stimuli that impair the structure and function of the nucleolus, and plays a key role in determining cell fate, such as apoptosis, senescence and autophagy. Autophagy is a conserved self-digestion process that degrades damaged components in cells in an orderly manner to maintain cell homeostasis. In recent years, accumulating evidence has demonstrated that a complex interaction exists between nucleolar stress and autophagy. Nucleolar stress can induce autophagy, and autophagy can in turn regulate nucleolar stress. This article reviews the complex relationship between nucleolar stress and autophagy, as well as their roles in disease pathogenesis, thereby providing a theoretical basis for targeting nucleolar stress- autophagy in the treatment of diseases and the development of new therapeutic strategies.

Vacuolar protein sorting 10 protein (VPS10P) domain receptors are a class of key neuronal sorting receptors that mediate the internalization and intracellular sorting of specific proteins in various cell types.This protein family consists of five type I transmembrane proteins: Sortilin,SorLA,SorCS1,SorCS2,and SorCS3.Recent studies have confirmed that this family plays significant regulatory roles in neuropsychiatric disorders, particularly depression. VPS10P domain receptors are intricately involved in the pathophysiological progression of depression through mechanisms such as regulating neuroplasticity and maintaining the homeostasis of neurotransmitter systems.Despite recent advancements,the interactions among VPS10P domain receptors and their specific mechanistic roles in depression warrant further investigation. This article focuses on VPS10P domain receptors,systematically elaborating on how each member influences the brain-derived neurotrophic factor (BDNF) signaling pathway,as well as their mechanistic contributions and current research status in the context of depression. By integrating existing knowledge and clarifying future research trajectories, this article aims to provide a robust theoretical foundation for breakthroughs in understanding the mechanisms of depression and the development of novel diagnostic and therapeutic targets.

Alzheimer's disease (AD) is a globally prevalent neurodegenerative disorder characterized by a chronic,progressive course and an increasing incidence.It gradually impairs patients' memory and cognitive functions, ultimately compromising their ability to perform basic activities of daily living. This review systematically summarizes the clinical diagnostic biomarkers of AD and analyzes the impact of exercise on key biomarkers,along with their underlying mechanisms. By integrating current literature and mechanistic evidence, we outline the core pathological mechanisms of AD and the corresponding biomarker systems, and conclude the regulatory effects of exercise on these biomarkers based on experimental evidence. Findings indicate that exercise ameliorates AD pathology through multiple mechanisms: by activating the PI3K/AKT pathway and enhancing microglial phagocytosis to reduce β-amyloid (Aβ) deposition; by inhibiting tau hyperphosphorylation; by activating the triggering receptor expressed on myeloid cells 2 (TREM2) pathway to suppress neuroinflammation; and by regulating oxidative stress through the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway, thereby restoring energy metabolism and maintaining cognitive function. In conclusion, exercise modulates core AD biomarkers and mitigates disease progression, representing an effective non-pharmacological approach for the prevention and treatment of AD. Future research may focus on standardizing biomarker detection and developing dynamic monitoring techniques to enable precise evaluation of exercise interventions and the formulation of personalized exercise prescriptions.

In recent years, the global prevalence of type 2 diabetes mellitus (T2DM) has continued to rise,significantly elevating the risk of multiple complications such as cardiovascular disease, and rendering it one of the most pressing contemporary public health concerns.The intestinal microecology, maintained by the intestinal microbiota, microbial metabolites, and the intestinal barrier, plays a crucial role in maintaining host health and modulating disease onset and progression. Resistant starch (RS) is a class of starch that resists digestion in the small intestine, reaches the large intestine intact,and undergoes fermentation by the intestinal microbiota. As an emerging functional food component for improving glucose and lipid metabolism,RS can increase the abundance of beneficial bacteria (including Lachnospiraceae, Akkermansia, Blautia, Firmicutes, Lactobacillus, and Bifidobacterium ) and the levels of beneficial metabolites (such as butyrate, propionate, and acetate) in T2DM mouse models, thereby effectively alleviating hyperglycemia-induced damage in these animals. The underlying mechanisms may involve the regulation of immune responses, oxidative stress, inflammatory responses, and glucose and lipid metabolism. This review aims to summarize research progress on how resistant starch ameliorates T2DM by modulating the intestinal microecology, thereby providing novel strategies and insights for the clinical diagnosis, treatment, and future investigation of T2DM.

Hypoxic training is a training method that enhances the body’s adaptation to hypoxia by combining high-altitude or simulated hypoxic environments with exercise stimulation in order to improve exercise performance and health. Its main physiological mechanism is to promote physiological adaptation by activating the hypoxia-inducible factors (HIFs) signaling pathway. This review summarizes the molecular structural characteristics of HIF isoforms (HIF-1α, HIF-2α, and HIF-3α) and their differential regulatory mechanisms in four hypoxic training modalities, aiming to provide a molecular-level theoretical basis for optimizing hypoxic training regimens.

YAP/TAZ are core transcriptional coactivators of the Hippo pathway and have recently been identified as key integrative hubs in renal mechanotransduction and cell fate determination. This article systematically reviews recent research progress on YAP/TAZ in kidney diseases, with a focus on their molecular mechanisms regulating cellular metabolism, proliferation, cell death (autophagy, apoptosis and ferroptosis), mechanical stress sensing, and inflammatory epigenetic reprogramming in renal fibrosis and renal cell carcinoma. Furthermore, we propose that developing drugs targeting the YAP/TAZ-TEAD interaction or highly specific mechanosensors, combined with emerging strategies such as PROTAC degradation technology and epigenetic editing, offers highly promising new directions for the treatment of kidney diseases.

As a crucial micro-organ of the skin, the hair follicle not only fulfills hair production functions but also participates in skin barrier maintenance, wound repair, and regional immune regulation. With the rising prevalence of hair loss disorders, hair follicle regeneration has become a cutting-edge focus in skin regenerative medicine. Traditional pharmacological interventions and surgical hair transplantation are constrained by issues such as inconsistent therapeutic effects, high costs, and potential complications, making large-scale clinical adoption challenging. In recent years,advances in understanding the hair follicle regulatory network, stem cell niche, and epithelial-mesenchymal interactions have gradually shifted hair follicle regeneration strategies from "structural replacement" toward "functional reconstruction", revealing broad application prospects. This review systematically elaborates on the histological characteristics and physiological functions of hair follicle, summarizes core molecular pathways in hair follicle regeneration and their pathophysiological relevance in conditions such as androgenetic alopecia and alopecia areata, and highlights innovative therapeutic strategies based on stem cell therapy, tissue engineering, and smart biomaterials. The aim is to provide a theoretical foundation and strategic reference for the accurate elucidation of hair loss mechanisms and their clinical translation.

The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, yet genetic and environmental factors alone cannot fully account for its pathogenesis. The role of the biological clock and its regulated circadian rhythms in metabolic diseases has garnered increasing attention. This article focuses on the circadian rhythm and glucose metabolism systems, elaborating on their multi-level regulatory structures and the key mechanisms underlying T2DM following their disruption. Central-peripheral clock desynchronization and metabolic rhythm disorders in the liver and pancreas are considered core drivers of insulin resistance and hyperglycemia, with environmental zeitgebers and gut microbiota exerting amplifying and sustaining effects. Research indicates that circadian disruption affects T2DM not through a single pathway, but via multi-level mechanisms, including dysregulation of central time signals, temporal misalignment of peripheral metabolic organs, and circadian remodeling of gut microbiota, ultimately leading to systemic dysregulation of the body's glucose metabolism network. From the perspective of systemic rhythm imbalance, this article provides an integrative review of the key mechanisms by which circadian disruption promotes the onset and development of T2DM, offering a theoretical basis and translational directions for early warning and intervention of T2DM from a circadian rhythm perspective.

The high mortality rate of digestive system tumors is closely associated with their unique metabolic reprogramming, yet the regulatory role of circular RNAs (circRNAs) in this process has not been systematically elucidated. This review aims to fill this knowledge gap by systematically constructing a multi-dimensional regulatory network of circRNA-mediated metabolic reprogramming in digestive system tumors. We elaborate on the precise regulatory functions of circRNAs in key metabolic pathways including glycolysis, glutamine metabolism, lipid metabolism, and mitochondrial function, through core mechanisms such as functioning as competing endogenous RNAs (ceRNAs), encoding functional micropeptides, and interacting with RNA-binding proteins. The review specifically analyzes the distinct regulatory networks of circRNAs in major digestive system tumors, including hepatocellular carcinoma, gastric cancer, esophageal cancer, and colorectal cancer, and discusses their translational potential as diagnostic biomarkers and therapeutic targets. These studies not only establish the theoretical role of circRNAs as key nodes in the metabolic reprogramming network but also lay a crucial foundation for their clinical translation: circRNAs demonstrate potential as highly stable liquid biopsy biomarkers and as novel targets for metabolism-oriented therapies. Although challenges remain in targeted delivery and standardized biomarker validation, future efforts such as the development of intelligent delivery systems and the advancement of multicenter clinical validation hold promise for targeting the circRNA-metabolism axis to provide innovative strategies for the precise diagnosis and treatment of digestive system tumors.