19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective:To analyze the clinical phenotype and gene mutation of a genetic coagulation factor Ⅻ(FⅫ)deficiency pedigree and explore the molecular pathogenesis.Methods:The activated partial thromboplastin time(APTT)and FⅫ activity(FⅫ:C)were detected by clotting method.The FⅫ antigen(FⅫ:Ag)was tested with ELISA.All exons and flanks of F12 gene were determined by Sanger sequencing.ClustalX-2.1-win,PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site,forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.Results:The APTT of the proband prolonged to 71.3 s.The FⅫ:C and FⅫ;Ag were decreased to 5％and 6％,respectively.There were two heterozygous missense mutations c.580G＞T and c.1681G＞A detected in exon 7 and exon 14 of F12 gene,resultingin p.Gly175Cys and p.Gly542Ser,severally.Proband's father carried the p.Gly175Cys heterozygous mutation,while mother,brother and daughter had the p.Gly542Ser heterozygous mutation.Software analysis showed that both Gly175 and Gly542 were conserved,the two mutations were harmful and when mutations had occurred,the corresponding sites affected the protein local structure.Conclusion:The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FⅫ deficiency pedigree.The p.Gly175Cys mutation has been detected for the first time in the world.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.

Background: Platform work offers flexibility and autonomy to workers, but there are concerns about the impacts of excessive labor control exercised by digital platforms using algorithmic management. This study assessed the level of labor control exerted by digital platforms and explored its associations with psychosocial work conditions and workers' mental well-being. Methods: A total of 487 location-based platform workers in Taiwan, encompassing ride-hailing, delivery, and house chore services, participated in this questionnaire survey. A 5-item scale was created to assess platform-mediated labor control. Psychosocial work conditions, including demands, job control, work rewards, and mental well-being, including burnout and self-rated mental health status, were assessed using validated instruments. Cronbach's α and principal component analysis were employed to assess the validity of the labor control scale. Logistic regression analysis and path analysis were conducted to investigate the relationship between labor control and workers' mental health. Results: Exploratory factor analyses confirmed the structural validity and the internal consistency of the scale. Logistic regression models revealed that higher levels of labor control were associated with an increased risk of burnout and poorer mental health. Path analyses further indicated that higher labor control through digital platforms raised mental health risks by increasing job demands. Conclusion Algorithmic management is associated with increased stress among platform workers as they try to meet the platform's performance metrics.

Background: Platform work offers flexibility and autonomy to workers, but there are concerns about the impacts of excessive labor control exercised by digital platforms using algorithmic management. This study assessed the level of labor control exerted by digital platforms and explored its associations with psychosocial work conditions and workers' mental well-being. Methods: A total of 487 location-based platform workers in Taiwan, encompassing ride-hailing, delivery, and house chore services, participated in this questionnaire survey. A 5-item scale was created to assess platform-mediated labor control. Psychosocial work conditions, including demands, job control, work rewards, and mental well-being, including burnout and self-rated mental health status, were assessed using validated instruments. Cronbach's α and principal component analysis were employed to assess the validity of the labor control scale. Logistic regression analysis and path analysis were conducted to investigate the relationship between labor control and workers' mental health. Results: Exploratory factor analyses confirmed the structural validity and the internal consistency of the scale. Logistic regression models revealed that higher levels of labor control were associated with an increased risk of burnout and poorer mental health. Path analyses further indicated that higher labor control through digital platforms raised mental health risks by increasing job demands. Conclusion Algorithmic management is associated with increased stress among platform workers as they try to meet the platform's performance metrics.

Background: Platform work offers flexibility and autonomy to workers, but there are concerns about the impacts of excessive labor control exercised by digital platforms using algorithmic management. This study assessed the level of labor control exerted by digital platforms and explored its associations with psychosocial work conditions and workers' mental well-being. Methods: A total of 487 location-based platform workers in Taiwan, encompassing ride-hailing, delivery, and house chore services, participated in this questionnaire survey. A 5-item scale was created to assess platform-mediated labor control. Psychosocial work conditions, including demands, job control, work rewards, and mental well-being, including burnout and self-rated mental health status, were assessed using validated instruments. Cronbach's α and principal component analysis were employed to assess the validity of the labor control scale. Logistic regression analysis and path analysis were conducted to investigate the relationship between labor control and workers' mental health. Results: Exploratory factor analyses confirmed the structural validity and the internal consistency of the scale. Logistic regression models revealed that higher levels of labor control were associated with an increased risk of burnout and poorer mental health. Path analyses further indicated that higher labor control through digital platforms raised mental health risks by increasing job demands. Conclusion Algorithmic management is associated with increased stress among platform workers as they try to meet the platform's performance metrics.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.