Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective:To investigate the clinical characteristics of children with Chikungunya fever.Methods:This retrospective cohort study analyzed clinical data of 91 children with Chikungunya fever at the Department of Pediatrics, Foshan women and Children Hospital between July 2025 and August 2025. The patients were divided into four groups based on onset-age: 0-<1 year, 1-<3 years, 3-<6 years, and 6-14 years. One-way ANOVA and chi-square tests were used to compare the clinical features of children with Chikungunya fever at different ages.Results:Among the 91 children with chikungunya fever, 55 were male and 36 were female, with an onset age of 6 (2, 11) years, age groups comprised 0-<1 year (10 cases), 1-<3 years (13 cases), 3-<6 years (17 cases) and 6-14 years (51 cases). Fever occurred in 87 cases (96%), with 50 cases (57%) had high fever. Skin rash was observed in 89 cases (98%), and 60 cases (67%) had a generalized rash. Joint pain was reported in 57 cases (63%), among which 35 cases (61%) had pain in two or more locations, with the knee involved in 21 cases (37%), the ankle in 15 cases (26%), and the wrist in 6 cases (11%).The knee was the most commonly affected joint 21 cases (37%), followed by the ankle 15 cases (26%) and wrist 6 cases (10%). Joint ultrasound was performed in 31 cases (34%), all showed joint effusion, including 8 cases (26%) without complaints of joint pain. The incidence of high fever was significantly lower in the 3-<6 years and 6-14 years groups compared to the 0-<1 year group (both P<0.05). The 6-14 years group also had a lower incidence of high fever than the 1-<3 years group ( P<0.05). The 1-<3 years group had longer duration of fever than the 3-<6 years and 6-14 years groups (both P<0.05). The incidence of joint pain was higher in the 3-<6 years and 6-14 years groups compared to the 1-<3 years group (both P<0.05), and higher in the 6-14 years group than in the 3-<6 years group ( P=0.007). Among all 91 children, 22 cases (24%) had abnormal liver function, 49 cases (54%) showed elevated lactate dehydrogenase (LDH), and 2 cases (2%) had elevated creatine kinase. The proportions of elevated aspartate aminotransferase (AST) and LDH were higher in the 0-<1 year and 1-<3 years groups compared to the 3-<6 years and 6-14 years groups (all P<0.05). Conclusions:The clinical characteristics of children with Chikungunya fever vary among children of different ages. Children in the 0-<3 years are more prone to high fever with longer duration and generalized maculopapular rash, while the children in the 6-14 years have have a higher proportion of joint pain, and joint ultrasound revealed effusion in all examined children. AST and LDH levels are elevated in the 0-<3 years groups.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P＜0.05 or P＜0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P＜0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P＜0.05 or P＜0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P＜0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P＜0.05 or P＜0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P＜0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P＜0.05 or P＜0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P＜0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.

Objective:To investigate the clinical characteristics of children with Chikungunya fever.Methods:This retrospective cohort study analyzed clinical data of 91 children with Chikungunya fever at the Department of Pediatrics, Foshan women and Children Hospital between July 2025 and August 2025. The patients were divided into four groups based on onset-age: 0-<1 year, 1-<3 years, 3-<6 years, and 6-14 years. One-way ANOVA and chi-square tests were used to compare the clinical features of children with Chikungunya fever at different ages.Results:Among the 91 children with chikungunya fever, 55 were male and 36 were female, with an onset age of 6 (2, 11) years, age groups comprised 0-<1 year (10 cases), 1-<3 years (13 cases), 3-<6 years (17 cases) and 6-14 years (51 cases). Fever occurred in 87 cases (96%), with 50 cases (57%) had high fever. Skin rash was observed in 89 cases (98%), and 60 cases (67%) had a generalized rash. Joint pain was reported in 57 cases (63%), among which 35 cases (61%) had pain in two or more locations, with the knee involved in 21 cases (37%), the ankle in 15 cases (26%), and the wrist in 6 cases (11%).The knee was the most commonly affected joint 21 cases (37%), followed by the ankle 15 cases (26%) and wrist 6 cases (10%). Joint ultrasound was performed in 31 cases (34%), all showed joint effusion, including 8 cases (26%) without complaints of joint pain. The incidence of high fever was significantly lower in the 3-<6 years and 6-14 years groups compared to the 0-<1 year group (both P<0.05). The 6-14 years group also had a lower incidence of high fever than the 1-<3 years group ( P<0.05). The 1-<3 years group had longer duration of fever than the 3-<6 years and 6-14 years groups (both P<0.05). The incidence of joint pain was higher in the 3-<6 years and 6-14 years groups compared to the 1-<3 years group (both P<0.05), and higher in the 6-14 years group than in the 3-<6 years group ( P=0.007). Among all 91 children, 22 cases (24%) had abnormal liver function, 49 cases (54%) showed elevated lactate dehydrogenase (LDH), and 2 cases (2%) had elevated creatine kinase. The proportions of elevated aspartate aminotransferase (AST) and LDH were higher in the 0-<1 year and 1-<3 years groups compared to the 3-<6 years and 6-14 years groups (all P<0.05). Conclusions:The clinical characteristics of children with Chikungunya fever vary among children of different ages. Children in the 0-<3 years are more prone to high fever with longer duration and generalized maculopapular rash, while the children in the 6-14 years have have a higher proportion of joint pain, and joint ultrasound revealed effusion in all examined children. AST and LDH levels are elevated in the 0-<3 years groups.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

Objective To explore the characteristics of blood vitamins A, B2, B6, B12, D, E, K1, K2 and folic acid and their correlation with severity in patients with metabolic-related fatty liver disease (MAFLD). Methods　From September to December 2022, a total of 473 cases of residents were recruited through community MAFLD screening activities and their health information was obtained through questionnaire survey and physical examination. The severity of hepatic steatosis was determined with FibroScan, and vitamin concentrations were determined with liquid chromatography-tandem mass spectrometry. Two independent samples' t-tests were used to assess the differences between the two groups, and univariate chi-square tests and multivariate logistic regression analysis were used to explore the related factors of MAFLD. Results　Of the 473 inhabitants, 195 (41.23%, 195/473) met the diagnostic criteria for MAFLD, including mild 43 (22.05%, 43/195) cases of fatty liver, 88 (45.13%, 88/195) cases of moderate fatty liver, and 64 (32.82%, 64/195) cases of severe fatty liver. Using healthy residents collected during the same period as controls, the overall mean of vitamins A, E, K1, and K2 in the MAFLD group was higher than that of the healthy group, with a statistical difference (P<0.05). Furthermore, the concentrations of vitamins A, E, K1 and K2 increased with the severity of fatty liver [R=0.149, P=0.004; R=0.245, P<0.001; R=0.110, P=0.032; R=0.129，P=0.012]. There were statistically significant differences (P<0.05) in the blood levels of vitamin A and E between patients with moderate or severe fatty liver and the healthy population. The blood vitamins K1 and K2 in severe fatty liver patients were also different from those of healthy people (P<0.05). However, there was no significance between folic acid, vitamin D, B2, B6, B12, and MAFLD (P>0.05). Through univariate chi-square analysis and multivariate logistic regression analysis, it was found that male [Wald=5.789, P=0.034，OR=1.598(1.037-2.463)] and vitamin E≥8.13 μg/mL[Wald=14.632，P<0.001，OR=2.378(1.522-3.674)] were risk factors for moderate and severe MAFLD. Conclusions The concentrations of vitamin A, E, and K in the blood are increased in patients with MAFLD compared to the healthy population, and they are positively correlated with the severity of MAFLD. ale gender and high levels of vitamin E may be related to moderate to severe MAFLD.

OBJECTIVE To investigate the role and mechanism of microRNA-125b (miR-125b) in downregulating ion channel-related protein expression in a cardiac hypertrophy model.METHODS① In vivo:Lentiviral vectors for miR-125b overexpression and knockdown were constructed,and male C57BL/6 mice were divided into the following groups:sham group (thoracotomy without virus injection),LV-miR-125b group (mmu-miR-125b mimic),LV-miR-125b-inhibitor group (mmu-miR-125b-inhibitor),and negative control group (LV-NC).The mice were raised under normal conditions for 4 weeks.The ultrastructural changes in myocardium tissue sections of LV-miR-125b mice were observed using trans-mission electron microscopy.The cardiac hypertrophy model in mice was established using thoracic aortic constriction (TAC).Echocardiography was performed to measure ejection fraction (EF) and frac-tional shortening (FS),and the ratio of heart weight to body weight (HW/BW),ratio of heart weight to tibia length (HW/TL),as well as the expression level of the myocardial hypertrophy marker β-myosin heavy chain (β-MHC) were calculated to evaluate the success of the TAC-induced hypertrophy model.Subse-quently,C57BL/6 mice were divided into four groups:Sham group,TAC model group,LV-miR-125b-inhibitor+TAC group,and LV-NC+TAC group.Protein expression levels of cardiac sodium channel (Nav1.5) and calcium channel (Cav1.2) were detected using Western blotting.RT-qPCR was performed to assess the levels of miR-125b and mRNA expression of myocardial hypertrophy markers,including atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and β-MHC.② In vitro:Primary cultured neonatal Kunming mouse cardiomyocytes were divided into four groups:cell control group (no treatment),miR-125b overexpression group,miR-125b-inhibitor group,and negative control group (NC).RT-qPCR was used to detect the levels of miR-125b,ANP,BNP,and β-MHC.Western blotting and immunofluorescence were performed to assess the expression levels of Nav1.5 and Cav1.2 in the cardiomyocytes.Luciferase reporter gene assay was used to evaluate the direct effect of miR-125b on the target proteins Nav1.5 and Cav1.2.RESULTS ① In vivo:Compared to the Sham group,the TAC model mice showed significantly increased the ratio of heart weight to body weight (HW/BW),the ratio of heart weight to tibia length (HW/TL),and expression levels of the myocardial hypertrophy marker β-MHC (P＜0.05),indicating the successful establishment of the TAC model.Furthermore,miR-125b expression was significantly elevated in the TAC model group (P＜0.01).In the LV-miR-125b group,compared to the LV-NC group,the expression levels of myocardial hypertrophy markers ANP,BNP,and β-MHC were significantly increased (P＜0.01),while the ejection fraction (EF) and fractional short-ening (FS) values of the mice were significantly reduced (P＜0.01).Additionally,Additionally,myocardium ultrastructure of LV-miR-125b group was damaged.Compared to the LV-NC+TAC group,the LV-miR-125b-inhibitor+TAC group showed a significant increase in ejection fraction (EF) and fractional shortening (FS) values (P＜0.05).Additionally,the levels of Nav1.5 and Cav1.2 in myocardium tissue were signifi-cantly elevated in the LV-miR-125b-inhibitor+TAC group compared to the LV-NC+TAC group (P＜0.05).② In vitro:Compared to the NC group,the miR-125b overexpression group showed a significant increase in miR-125b expression (P＜0.01),as well as elevated levels of ANP,BNP,and β-MHC (P＜0.01).However,miR-125b-inhibitor significantly reversed the increases in ANP,BNP,and β-MHC (P＜0.01).Western blotting and immunofluorescence results showed that,compared to the NC group,the miR-125b mimic group exhibited significantly decreased levels of Nav1.5 and Cav1.2 (P＜0.01),while miR-125b-inhibitor led to an increase in the levels of both Nav1.5 and Cav1.2.Luciferase assay results demon-strated that miR-125b directly binds to the ion channel proteins Nav1.5 and Cav1.2,encoded by the SCN5A and CACNA1C genes.CONCLUSION miR-125b promotes the development of cardiac hyper-trophy by inhibiting the voltage-gated ion channel proteins Nav1.5 and Cav1.2 Inhibition of miR-125b expression improves cardiac hypertrophy.