1.The Role and Regulatory Mechanisms of FOXO1 in Hepatic Lipid Deposition
Meng JIA ; Fang-Hui LI ; Shi-Zhan YAN ; Ai-Ju LI ; Yi-Le WANG ; Pin-Shi NI ; Jia-Han HE ; Yin-Lu LI
Progress in Biochemistry and Biophysics 2026;53(4):905-919
Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.
2.Renal fibrosis: research progress on mechanisms and therapeutic strategies
Cheng-Xiao YIN ; Jia-Rui FAN ; Xiao-Gang DU
Kidney Research and Clinical Practice 2026;45(1):22-35
Renal fibrosis (RF) is a prevalent clinical symptom of numerous chronic kidney illnesses and a significant pathological alteration in end-stage renal disease resulting from various mechanisms, such as abnormally activated signaling pathways, microRNAs, aging, autophagy disorders, and fibrotic ecological niches, all of which contribute to RF development. Inhibiting, blocking, or delaying the aforementioned mechanisms may yield novel approaches for treating RF. This article explores advancements in the comprehension of the mechanisms and therapeutic approaches for RF.
3.Population composition and seasonal distribution of mosquitoes in Laoshan District, Qingdao City
Zi-long TANG ; Na YU ; Yang YU ; Fan YIN ; Bing-hui LI ; Hong-yu WANG ; Ke-jia HUANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):114-120
Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P < 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P< 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.
4.Research advances in the disease burden of viral hepatitis in China
Jian LI ; Fuzhen WANG ; Zhongdan CHEN ; Jinlei QI ; Ailing WANG ; Fanghui ZHAO ; Yuanyuan KONG ; Jing SUN ; Jiaqi KANG ; Zundong YIN ; Zhongfu LIU ; Jidong JIA ; Yu WANG
Journal of Clinical Hepatology 2025;41(2):221-227
Over the past three decades, China has made significant progress in the prevention and control of viral hepatitis, and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level; however, there is still a heavy disease burden of chronic viral hepatitis in China, which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China, analyzes existing problems and challenges, and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China, in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.
5.Treatment of Parkinson's Disease with Traditional Chinese Medicine by Regulating BDNF/TrkB Signaling Pathway: A Review
Lulu JIA ; Ying LI ; Jiale YIN ; Nan JIA ; Xiaoxi LIU ; Li LING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):315-322
Parkinson's disease(PD) is the second most common neurodegenerative disease in the world, which seriously affects the lives of patients. With the acceleration of aging process, the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However, the pathogenesis of PD is still unclear. According to reports, the brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrkB) signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra, which is closely related to neurophysiological processes such as neurogenesis, synaptic plasticity, neuroinflammation, and oxidative stress. It plays an important role in the occurrence and development of PD. At present, the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms, but with the increase of dose, the adverse reactions are significantly enhanced. Traditional Chinese medicine(TCM) has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food, economy, minor adverse reactions and multi-target action. Therefore, this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas, extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad, so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.
6.Association between mobile phone addiction and high myopia among college students
Jian YIN ; Zeshi LIU ; Yan LI ; Yangyang GONG ; Naichuan CHEN ; Yuqi ZHAO ; Jia SONG ; Yanping ZHANG
International Eye Science 2025;25(2):301-305
AIM:To analyze the association between mobile phone addiction and high myopia among college students.METHODS:We conducted a cross-sectional questionnaire survey in December 2022 on all students of a university in Shaanxi Province, and the questionnaire included socio-demographic characteristics, mobile phone addiction, high myopia, and lifestyle. Binary Logistic regression model was used to analyze the association between mobile phone addiction and high myopia among college students.RESULTS:A total of 19 952 college students were included. The prevalence of high myopia was 7.31%. The rate of mobile phone addiction was 25.68%, and the mobile phone addiction score was 37.59±13.38. The incidence of high myopia among college students with mobile phone addiction was higher than non-mobile phone addiction(P<0.001). After adjusting for socio-demographic characteristics and lifestyle, the risk of high myopia among college students with mobile phone addiction was 1.274 times(95%CI:1.131-1.434)higher than non-mobile phone addiction. For each point increase of total mobile phone addiction score, withdrawal symptoms score, salience score, social comfort score, and mood changes score, the risk of high myopia among college students increased by 0.9%(95%CI:1.005-1.013), 2.0%(95%CI:1.010-1.030), 2.6%(95%CI:1.010-1.043), 4.8%(95%CI:1.030-1.066), and 3.3%(95%CI:1.014-1.052), respectively.CONCLUSION:Mobile phone addiction is significantly associated with the increased risk of high myopia among college students, and early intervention of mobile phone use may reduce the risk of high myopia among college students.
7.Epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection in community populations in Xuhui District, Shanghai
Huiting WANG ; Yanfei GUO ; Chen CHEN ; Junhong YUE ; Qingqing JIA ; Fei WU ; Yanlu YIN ; Jiajie ZANG ; Fan WU
Shanghai Journal of Preventive Medicine 2025;37(10):803-812
ObjectiveTo analyze the epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection by conducting follow-up investigations among community residents who experienced their first SARS-CoV-2 infection between March and June 2022, so as to provide a scientific basis for predicting future epidemic trends and adjusting prevention and control strategies. MethodsA cohort study was conducted in Xuhui District, Shanghai. A total of 1 208 individuals with a documented primary SARS-CoV-2 infection between March and June 2022 were enrolled and followed-up longitudinally. Data were collected using structured questionnaire surveys to assess the reinfection rate, incidence density, and clinical manifestations of SARS-CoV-2 reinfection. A logistic regression model was used to analyze the influencing factors of SARS-CoV-2 reinfection. ResultsA total of 497 SARS-CoV-2 reinfection cases were observed among the 1 208 research subjects, with a reinfection rate of 41.14% and an incidence density of 0.63 cases per 1 000 person-days. The cumulative reinfection rates at 6, 9, 12, 15, and 18 months following the initial infection were 0.08%, 15.31%, 19.04%, 33.53%, and 38.25%, respectively. Compared with the primary infection, reinfection was more likely to be symptomatic, with a greater severity of fever, dry cough, sore throat, and runny nose. Being female, younger age, and symptom duration ≥7 days during the primary infection were identified as influencing factors for SARS-CoV-2 reinfection, while a higher socioeconomic status can reduce the risk of SARS-CoV-2 reinfection. ConclusionSARS-CoV-2 reinfection is relatively common and often symptomatic. Age, gender, income level, and the duration of symptoms during the primary infection are identified as infuencing factors for SARS-CoV-2 reinfection. Continuous monitoring of reinfection in the population is recommended, along with the development of effective strategies to mitigate the impact of reinfection.
8.Effects of dorsal raphe 5-hydroxytryptamine neurons on sleep quality and anxiety-like behavior in PCPA insomnia model rats
Quntao Li ; Tongyu Du ; Lei Jia ; Jiangwen Yin ; Yan Li
Acta Universitatis Medicinalis Anhui 2025;60(4):697-706
Objective :
To investigate the selective activation of 5-hydroxytryptamine neurons in the dorsal raphe nucleus(DRN5-HT) of rats with insomnia induced by p-chlorophenylalanine(PCPA) using chemical genetics techniques, and to explore whether it has a regulatory effect on comorbidities of insomnia and anxiety.
Methods :
32 male SD rats were randomly divided into control group, PCPA model group(PCPA group), chemical activation group(hM3Dq+CNO group), and chemical control group(hM3Dq+Saline group). The anxiety level of experimental rats was evaluated through open field experiments and elevated cross maze experiments.In vivoelectroencephalography(EEG) was used to record propofol induced sleep and cortical EEG changes, and immunofluorescence staining was used to observe changes in c-Fos positive protein expression in 5-HT neurons.
Results :
The behavioral results showed that compared with the chemical control group, the anxiety level of the chemical activation group was significantly lower(P<0.05), and sleep duration was significantly prolonged(P<0.05). The expression level of c-Fos positive protein in DRN5-HT neurons in the chemical activation group was higher(P<0.05). The EEG results showed that the percentage of δ-band power between the chemical activation group and the chemical control group was higher(P<0.05), the power percentage in the α-band was relatively low(P<0.05).
Conclusion
Chemical activation of 5-HT neurons in the DRN region can improve anxiety levels and increase sleep duration in PCPA induced insomnia rats.
9.Bioinformatics analysis and experimental validation of BPS and BPF on signaling pathways of male reproductive system damage
Yu SHI ; Jingzhi LI ; Hongqiang CHEN ; Shimeng ZHOU ; Na WANG ; Jia CAO ; Li YIN ; Wenbin LIU
Journal of Jilin University(Medicine Edition) 2025;51(2):460-470
Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1%DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P<0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P<0.05),while the viabilities of TM3 cells in other groups had no significant changes(P>0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P<0.05),the expression levels of PI3K protein were decreased(P<0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P<0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P<0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P<0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P<0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P<0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P<0.05),and the expression levels of IFT80 mRNA(P<0.01)and Bax protein(P<0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P<0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P<0.05),while the expression level of RNF130 mRNA was increased(P<0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P<0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.
10.Itaconic acid improves vascular endothelial dysfunction in diabetic mice by inhibiting endothelial cell apoptosis
Jia TANG ; Yuehui YIN ; Yunlin CHEN ; Jian YANG ; Fuwei ZHANG ; Luning WANG
Journal of Chongqing Medical University 2025;50(9):1195-1201
Objective:To investigate the protective effect and mechanism of 4-octyl itaconate(4-OI)on vascular endothelial function in diabetic mice,since endothelial dysfunction is the key and initial factor for vascular complications in diabetes.Methods:The db/db mice were used to establish a mouse model of diabetes,and high glucose(HG)-induced human umbilical vein endothelial cells(HUVECs)were used to establish a cell model of diabetes.After 4-OI treatment,HE staining,Masson staining,and reticular fiber staining were used to observe pathological changes of the thoracic aorta in the control group,the model group,and the intervention group;Western blot was used to measure the expression of α-smooth muscle actin(α-SMA),a marker for endothelial fibrosis;immuno-fluorescence assay was used to measure the expression levels of Bcl-2-associated X protein(BAX)and B-cell lymphoma-2(Bcl-2)in the thoracic aorta of mice in the control group,the model group,and the intervention group;immunoblotting was used to observe the effect of 4-OI intervention on the expression of BAX,Bcl-2,and the proteins associated with the cytochrome C(CytC)/cysteinyl aspartate specific proteinase(caspase)pathway in HG-induced HUVECs.Results:The results showed that 4-OI could significantly improve vascular endothelial dysfunction in db/db diabetic mice.Compared with the model group,the intervention group had a significant increase in the expression of Bcl-2(0.73±0.07 vs.0.52±0.04,F=49.380,P=0.009)and a significant reduction in the expression of BAX(1.41±0.14 vs.1.89±0.12,F=37.270,P=0.008)after 4-OI treatment.In the cell model of HUVECs induced by HG,compared with the high glucose group,the intervention group had a sig-nificant increase in the expression of Bcl-2(1.22±0.04 vs.0.81±0.09,F=75.410,P<0.001)and a significant reduction in the expres-sion of BAX(0.83±0.04 vs.1.12±0.04,F=268.100,P<0.001)after 4-OI treatment,as well as significant reductions in the expres-sion of CytC(0.61±0.03 vs.1.01±0.03,F=234.000,P<0.001),caspase-9(0.62±0.03 vs.1.04±0.04,F=164.300,P<0.001),and caspase-3(0.92±0.06 vs.1.74±0.04,F=424.100,P<0.001).Conclusion:In conclusion,4-OI inhibits vascular endothelial cell apoptosis in diabetic mice by affecting the expression of the CytC/Caspase pathway factors,thereby improving vascular endothelial dys-function in diabetes.


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