The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway is a cornerstone of host innate immunity, playing a central role in detecting cytosolic double-stranded DNA of both endogenous and exogenous origins. Upon activation, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which binds and activates STING to trigger downstream immune responses, including the production of type I interferons and proinflammatory cytokines. Emerging studies highlight the cGAS-STING pathway as a promising therapeutic target for preventing and treating diverse pathologies, with particularly transformative potential in anticancer therapies. In this review, we dissect the key findings, functions, and associated components of the cGAS-STING pathway. In addition, we emphasize the factors that upregulate or downregulate the pathway, as well as the role of the cGAS-STING pathway in health and disease. By integrating mechanistic insights with clinical perspectives, this review aims to bridge fundamental discoveries with therapeutic applications of cGAS-STING biology.
Humans ; Nucleotidyltransferases/metabolism* ; Membrane Proteins/metabolism* ; Animals ; Immunity, Innate/physiology* ; Signal Transduction/physiology* ; Neoplasms/metabolism*

The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

OBJECTIVES: Depression is a common negative emotion that can significantly impact physical and mental health. Due to their occupational characteristics, medical staff are more susceptible to depression compared to the general population. This study aims to explore the influence of future-oriented coping on depression among medical staff and the mediating roles of psychological resilience and perceived stress, providing theoretical guidance for depression intervention strategies in this group. METHODS: A cross-sectional survey was conducted among medical staff at a tertiary hospital using convenience sampling. Data were collected via the "Wenjuanxing" platform. A total of 754 questionnaires were distributed; after excluding invalid responses (e.g., duplicate IPs or insufficient completion time), 655 valid questionnaires were retained (valid response rate: 86.87%). Instruments included a demographic questionnaire, the Future-Oriented Coping Scale, the Connor-Davidson Resilience Scale, the Perceived Stress Scale, and the Self-Rating Depression Scale. All scales demonstrated high internal consistency (Cronbach's α>0.88) and validity. SPSS 27.0 was used for descriptive analysis, and PROCESS macro (Model 6) was used to test the chain mediation model. Harman's one-factor test was applied to control for common method bias. RESULTS: Descriptive analyses showed that future-oriented coping was positively correlated with psychological resilience and negatively correlated with perceived stress and depression. Mediation analysis revealed that future-oriented coping significantly predicted lower depression levels among medical staff (β=-0.283, P<0.001). Psychological resilience partially mediated the relationship (effect size=-0.329, accounting for 34.13% of the total effect), as did perceived stress (effect size=-0.099, 10.27%). A significant chain mediation path was identified: "future-oriented coping → psychological resilience → perceived stress → depression" (effect size=-0.253, 26.24%). The total indirect effect accounted for 70.64% of the overall effect, highlighting the substantial role of the mediating pathways. CONCLUSIONS Future-oriented coping can reduce depressive symptoms in medical staff, with psychological resilience and perceived stress serving as key mediators in a chain structure. These findings suggest that enhancing future-oriented coping strategies and psychological resilience may improve stress adaptation and reduce depression levels in this population.
Humans ; Adaptation, Psychological ; Resilience, Psychological ; Cross-Sectional Studies ; Depression/psychology* ; Surveys and Questionnaires ; Stress, Psychological/psychology* ; Male ; Female ; Adult ; Middle Aged ; Medical Staff/psychology* ; Occupational Stress/psychology*

OBJECTIVES: Anxiety is a common negative emotion. Under current social circumstances, university young teachers face multiple stressors and are more prone to anxiety, seriously threatening their physical and mental health. This study aims to investigate the impact of job insecurity on anxiety of university young teachers, while exploring the mediating roles of perceived stress and insomnia on this relationship. METHODS: Using convenience sampling, young teachers from a general university in a Chinese province were surveyed online. Scores of the Job Insecurity Scale, Perceived Stress Scale, Athens Insomnia Scale-Short Form, and Generalized Anxiety Disorder Scale were collected. A chain mediation analysis was conducted using the PROCESS macro. RESULTS: A total of 798 subjects were finally included. The detection rate of anxiety among university young teachers was 36.47%. Mediation analysis showed that job insecurity not only had a direct effect on anxiety, but also indirectly affected anxiety via perceived stress (46.42% of the total effect) and insomnia (7.45%), as well as through the chain-mediating path of perceived stress→ insomnia (13.18%; all P<0.05). CONCLUSIONS Job insecurity is a significant predictor of anxiety in young university faculty. Perceived stress and insomnia serve as sequential mediators in this relationship. Targeted interventions addressing job insecurity, stress perception, and sleep disturbances, alongside efforts to improve mental health literacy and the working environment, may help promote the overall well-being of university young teachers.
Humans ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Universities ; Female ; Anxiety/psychology* ; Male ; Stress, Psychological/psychology* ; Adult ; Faculty/psychology* ; Surveys and Questionnaires ; China/epidemiology* ; Occupational Stress ; Job Security

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People