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.

Chikungunya fever is an infectious disease caused by the Chikungunya virus(CHIKV),an arbovirus.In recent years,large-scale outbreaks of Chikungunya fever have occurred in many parts of the world,posing a serious challenge to public health.Perinatal infection of CHIKV and its impact on neonates have attracted growing attention.This article aims to introduce the mechanisms and the influencing factors of mother-to-child transmission of CHIKV and to explore its impact on the nervous system in neonates.According to reported findings,CHIKV can cross the placental barrier,causing infection in the fetus,and can cross the blood-brain barrier,leading to various neurological diseases in neonates,such as microcephaly and encephalitis.In addition,factors influencing mother-to-child transmission include the maternal viral load and the stage of pregnancy at the time of infection.Through a review of current scholarly works,this article provides ideas and a theoretical basis for the prevention and control of mother-to-child transmission of CHIKV and for research into the mechanisms underlying CHIKV-induced brain injury in neonates.

Objective:To explore the association between sibling violence experience and emotional and behavioral problems.Methods:A Multistage stratified cluster sampling was used in Hunan province, 1735 participants from multiple-child family were recruited to survey the prevalence of sibling violence and the occurrence of emotional and behavioral problems with the Strength and Difficulties Questionnaires (SDQ).Results:According to SDQ total score, the rate of abnormal emotion and behavior in children and adolescents involved in sibling violence was higher than that in students who were not experienced sibling violence [45.6％ (236/518) vs.26.8％ (326/1217) ], the rate in bully-victim was higher than that in pure-victim and pure-bully [52.8％ (132/250) vs.37.9％ (74/195) vs.41.1％ (30/73) ].The rates in children and adolescents who were bullied and perpetrated more than 4 sub-types of sibling violence were 63.4％ (53/93) and 76.9％ (60/78).Conclusion:There is an association between sibling violence experience and emotional and behavioral problems among children and adolescents in rural areas.

OBJECTIVE: To investigate the inhibition effects of Tianshen Yizhi Recipe (TSYZR), a compound traditional Chinese herbal medicine, on decreased expression of nicotinic acetylcholine receptor (nAChR) and the neurotoxicity as well as lipid peroxidation induced by beta-amyloid peptide (Abeta) in human SH-SY5Y neuroblastoma cells. METHODS: The SH-SY5Y cells were treated by a certain concentration of TSYZR, and then exposed to Abeta(25-35). Methyl thiazolyl tetrazolium reduction assay was carried out to understand the influences of the drugs on cellular viability. Expressions of nAChR subunits (alpha3 and alpha7) at protein and mRNA levels were detected by Western-blotting and reverse transcription polymerase chain reaction, respectively. Lipid peroxidation was measured by thiobarbituric acid to observe the capacity of antioxidant of the drugs. RESULTS: TSYZR at a safe concentration could increase alpha7 protein in the cells, inhibit decreased expressions of alpha3 and alpha7 nAChR subunit proteins, prevent lower expression of alpha7 mRNA in SH-SY5Y cells induced by Abeta, reduce the neurotoxicity and lipid peroxidation resulting from Abeta, but had no significant effect on the lower expression of alpha3 mRNA. CONCLUSIONS: TSYZR can up-regulate the expression of alpha7 nAChR subunit protein and prevent decreased expressions of nAChRs and neurotoxicity as well as lipid peroxidation induced by Abeta. This drug may play an important therapeutic role in treatment of Alzheimer disease.