Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

Objective To investigate the biological functions of the ERG3 gene in Candida albicans and its potential value in antifungal therapy. Methods The ERG3 null mutant was constructed by the CRISPR/Cas9 technology. Gas chromatography-mass spectrometry, microbroth dilution method, hyphal induction and mouse systemic infection models were carried out to evaluate sterol metabolism, drug susceptibility, hyphal formation ability and pathogenicity in C. albicans. Results The disruption of the ERG3 gene led to disordered sterol metabolism in C. albicans with a significant increased level of episterol, 14α-methylfecosterol and ergosta-7,22-dienol. The ERG3 null mutant exhibited significantly reduced susceptibility to antifungal azole and polyene drugs, which suggested that ERG3 involve in regulating drug resistance. Although the disruption of ERG3 inhibited hyphal growth and biofilm formation, it did not significantly alter the pathogenicity of the strain in a mouse model of systemic fungal infection. Conclusion The ERG3 gene was a key regulator in the ergosterol synthesis pathway in C. albicans. Its deletion induced multi-drug resistance by reshaping sterol metabolism, while pathogenicity maintenance depended on compensatory mechanisms. This study provided critical insights for developing antifungal drugs targeting sterol metabolism and overcoming drug resistance.

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

This study investigates the material basis and mechanism of Arisaematis Rhizoma Preparatum in the treatment of chronic obstructive pulmonary disease(COPD) using animal experiments, component analysis, network pharmacology, and molecular docking. A mouse model of COPD was constructed by cigarette smoke and lipopolysaccharide(LPS). Blood gas analysis was performed to measure the pH and partial pressure of carbon dioxide(PCO_2) in the blood of the mice. Lung tissue sections were analyzed using HE staining, and the effects of Arisaematis Rhizoma Preparatum water extract on inflammatory factors(TNF-α, IL-6, and IL-1β) and the PI3K/AKT signaling pathway in the lung tissue of COPD model mice were studied by qPCR and Western blot. The composition of the Arisaematis Rhizoma Preparatum water extract was analyzed using UPLC Q-Exactive Orbitrap MS. The SwissTargetPrediction database was used to predict the targets of the chemical components in Arisaematis Rhizoma Preparatum. GeneCards, OMIM, TTD, PharmGKB and DrugBank disease databases were used to screen for COPD targets, and the potential targets of Arisaematis Rhizoma Preparatum in treating COPD were identified. A protein-protein interaction(PPI) network of intersection targets was constructed and analyzed using the STRING database and Cytoscape 3.9.0, and core genes were screened. GO functional analysis and KEGG pathway enrichment analysis were performed using R language, and molecular docking verification was conducted using AutoDock Vina software. The results of the animal experiments showed that Arisaematis Rhizoma Preparatum water extract improved pulmonary ventilation function in COPD model mice, reduced lung inflammatory cells, decreased alveolar cavities, and improved lung tissue condition. The levels of inflammatory factors TNF-α, IL-6 and IL-1β were decreased, and the phosphorylation levels of PI3K and AKT were inhibited. Fifty-two chemical components were identified from Arisaematis Rhizoma Preparatum, and 440 intersection targets related to COPD were found. Nine key components were screened, including hydroxyphenylethylamine, L-tyrosine, L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, methyl azelate, zingerone, 6-gingerol, linoleamide, and linoleoyl ethanolamine. Five core targets were identified, including AKT1, TNF, STAT3, ESR1, and IL1B. The PI3K/AKT pathway was identified as the key pathway for the treatment of COPD with Arisaematis Rhizoma Preparatum. Molecular docking results showed that 75% of the binding energies of key components and core targets were less than-5 kcal·mol~(-1), indicating good binding affinity. In conclusion, Arisaematis Rhizoma Preparatum may improve pulmonary ventilation function, enhance lung pathological morphology, and reduce pulmonary inflammation in COPD model mice by inhibiting the PI3K/AKT signaling pathway and downregulating TNF-α, IL-6, and IL-1β inflammatory factors. The material basis may be associated with L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, zingerone and 6-gingerol, and AKT1 and TNF may be the primary targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rhizome/chemistry* ; Humans ; Molecular Docking Simulation ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Signal Transduction/drug effects* ; Lung/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Interleukin-6/immunology*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal