Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

In recent years,academic misconduct has shown an alarming escalation trend.Particularly in the artificial intelligence environment,these improper behaviors have become more covert and complex,increasingly difficult to distinguish and identify.This study establishes a three-dimensional academic misconduct prevention system through enhancing stakeholder awareness,standardizing research integrity policies,and implementing advanced"dynamic adversarial"artificial intelligence generated content(AIGC)detection technologies(e.g.,tracing with blockchain and neural network fingerprinting,deep learning algorithms,multimodal and cross-lingual detection).By integrating cognition,institution,and technology dimensions,the framework constructs a"value-driven-institutional-safeguarded-technology-empowered"synergistic governance model.Within dynamic environments,these three elements interact through synergistic effects and positive feedback loops to form governance synergy,providing innovative solutions for academic integrity construction.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

In recent years,academic misconduct has shown an alarming escalation trend.Particularly in the artificial intelligence environment,these improper behaviors have become more covert and complex,increasingly difficult to distinguish and identify.This study establishes a three-dimensional academic misconduct prevention system through enhancing stakeholder awareness,standardizing research integrity policies,and implementing advanced"dynamic adversarial"artificial intelligence generated content(AIGC)detection technologies(e.g.,tracing with blockchain and neural network fingerprinting,deep learning algorithms,multimodal and cross-lingual detection).By integrating cognition,institution,and technology dimensions,the framework constructs a"value-driven-institutional-safeguarded-technology-empowered"synergistic governance model.Within dynamic environments,these three elements interact through synergistic effects and positive feedback loops to form governance synergy,providing innovative solutions for academic integrity construction.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective:To assess the prevalence of exercise addiction among college students and explore its relationship with negative emotion and exercise frequency.Methods:A total of 837 college students were enrolled from January 1, 2022 to December 31, 2022. The cross-sectional survey was administered using the exercise dependence scale revised(EDS-R) and the depression, anxiety, and stress scale 21 items (DASS-21). Data analysis was conducted with SPSS 26.0 software, including partial correlation analysis and hierarchical regression.Results:Among college students, the students in the group with risk and symptoms of exercise addiction accounted for 4.9%(EDS-R score (110.32±11.51), DASS-21-depression score 21.00(10.50, 25.00), DASS-21-anxiety score 21.00(11.50, 24.00), DASS-21-stress score 42.00(22.00, 47.50)). The students in the group without risk but with symptoms accounted for 42.53%(EDS-R score (60.02±12.91), DASS-21-depression score 8.00(1.00, 14.00), DASS-21-anxiety score 8.00(3.00, 14.00), DASS-21-stress score 15.00(4.00, 28.00)), and the students in the group without risk and symptoms accounted for 52.57%(EDS-R score (31.57±7.51), DASS-21-depression score 8.00(5.00, 12.00), DASS-21-anxiety score 7.00(3.00, 10.00), DASS-21-stress score 15.00(6.00, 21.00)). Exercise addiction scores were positively correlated with stress ( r=0.303, P<0.001), anxiety ( r=0.327, P<0.001), and depression ( r=0.259, P<0.001). The results of the hierarchical regression analysis also showed that the main risk variables were anxiety (△ R2=0.175, F=60.954) and exercise frequency (△ R2=0.044, F=21.401). Additionally, male college students had a higher risk of exercise addiction than female( P<0.01), but there was no gender difference in negative emotions( P>0.05). Conclusion:The college students were susceptible to developing an exercise addiction, especially among individuals with high exercise frequency and anxiety symptoms.It provides robust behavioral evidence in support of early detection and treatment of high-risk exercise addiction groups.

【Objective】 To analyze the characteristics and influencing factors of blood transfusion in patients undergoing hepatectomy with hydatid hepatica, so as to provide perioperative blood security of these patients. 【Methods】 A retrospective analysis was performed on 40 hydatid hepatica patients who underwent hepatectomy from June 2011 to June 2021, and they were divided into the transfusion group (n=15) and the non-transfusion group (n=25). The difference in basic information, operative information, blood routine, coagulation function, biochemical parameters and thromboelastogram between the two groups were compared, and the characteristics of perioperative blood transfusion were analyzed. 【Results】 Fifteen(37.5%, 15/40) patients undergoing hepatectomy received blood transfusion, among which 2(5%, 5/40), 10(25%, 10/40) and 11(27.5%, 11/40) received preoperative, intraoperative and postoperative transfusion, respectively. The average transfusion of suspended red blood cells, plasma and cryoprecipitate were 4.77 U, 1 355 mL and 11.9 U respectively, without any adverse reactions of blood transfusion occurred. The operative time, intraoperative blood loss, the number of patients with tumor diameter ≥10 cm/ diameter <10 cm, the number of patients with cholecystectomy, postoperative PT, postoperative APTT and average hospital stay in the transfusion group were higher than those in the non-transfusion group(P<0.05), and the postoperative FIB was lower than those in the non-transfusion group(P<0.05). The blood test results showed that the WBC, AST, ALT and INR 24h after operation were significantly higher than those before operation (P<0.05), while RBC, Hb, ALP, FIB and Angle were significantly lower than those before operation(P<0.05). There were statistically significant differences in WBC, RBC, Hb, ALT, ALP and INR between preoperative and postoperative 3~5 days(P<0.05). The differences of WBC, AST, ALT and FIB 3~5 days after surgery were statistically significant compared with 24 hours after surgery(P<0.05). 【Conclusion】 The size of hepatic hydatid mass, cholecystectomy, intraoperative blood loss, operative time, postoperative PT, postoperative APTT and postoperative FIB were important factors affecting perioperative blood transfusion after hepatectomy, and the main transfusion components were plasma and cryoprecipitate.

The coexistence of multiple symptoms of acquired immunodeficiency syndrome (AIDS) has caused serious distress to patients. Symptom management based on the premise of grasping the general situation of symptoms becomes the responsibility of the nursing staff. However, the development and use of symptom assessment tools for AIDS populations at China and abroad have not been effectively sorted out and clarified. This article summarizes and analyzes this situation in related fields, aiming to provide reference and basis for future research.