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:Mycoplasma genitalium (Mg) is an opportunity pathogenic microorganism mainly transmitted through sexual contact. In recent years, scholars have paid more attention to Mg infection and pathogenicity. This study was aimed to understand the condition of Mg in the genitourinary tract of different populations in China and provide evidence for further study of its pathogenic characteristics. Methods:Cross-section studies of Mg infection in the Chinese community were searched by China National Knowledge Infrastructure (CNKI), Wanfang digital database, SinoMed, Pubmed, and Web of Science from database construction to March 10 th, 2020. Studies were sifted and screened independently by two evaluators based on inclusion and exclusion criteria, and Meta-analysis was conducted with R 1.1.463. If I 2≤50%, the fixed-effect model should be adopted, if I 2>50%, the random effect model should be adopted, and through subgroup analysis, the source of heterogeneity should be found out as far as possible. Results:A total of 47 research articles were included in this article, all of which were medium and high-quality articles. There was no obvious publication bias, and the results were more reliable. The research contained 19 provinces and Hong Kong Special administrative region, including 519 healthy people, 10 504 patients from clinics or hospitals of sexual transmitted disease (STD), 3 200 on Gynecology and 1 624 on Urology, 1 082 patients with men who have sex with men(MSM), 1 842 patients with Female sex worker(FSW), and 3 691 patients with HIV/AIDS. The infection rate of Mg in the genitourinary tract of the healthy population was 0.94% (95% CI: 0.07%-2.78%), the infection rate of Mg was 11.58% (95% CI: 8.57%-14.97%), 15.22% (95% CI: 7.99%-24.27%), 7.32% (95% CI: 4.24%-11.16%) among patients from clinics or hospitals of STD, gynecology and urology respectively. The infection rate of MSM was 9.70% (95% CI: 3.06%-19.52%),the infection rate of FSW was 13.49% (95% CI: 11.97%-15.08%). The infection rate of Mg among HIV infected patients was 20.46% (95% CI: 13.67%-28.22%). Conclusions:The infection rate of Mg in a healthy population was low. Mg infection rate in the genitourinary tract of other groups was still higher, which is worthy of further attention.