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 study the clinical characteristics and risk factors of cow's milk protein allergy(CMPA)in infants less than 3 months old in Guangxi District.Methods From July 1 ,2012,to December 30,2014,infants less than 3 months old suspected of CMPA visiting the pediatric outpatient depart-ment of Maternal and Children Hospital of Guangxi Zhuang Autonomous Region were recruited,which included initial diagnosis and being transported from peripheral hospitals.Observation scale was formulated, attending physician screened patients and their senior made a definite diagnosis.All the infants underwent diagnostic algorithms and were followed up constantly.Results A total of 137 cases were divided into aller-gy group(n =51 )and control group(n =86).Two groups shared some common symptoms such as diarrhea, constipation,bloody stool,stomachache,gastroesophageal reflux(GER),indigestion,anorexia,feeding diffi-culties.Between the allergy group and control group the parameters such as feeding patterns (including breast feeding,mix feeding,formula feeding),improper deeding of food supplement,long-term use of antibiotics in neonatal period and parental atopy showed no significant differences(P ﹥0.05).The parameters in neonatal period including GER [20 cases (39.2%)vs.7 cases (8.1 %)],intake of cow's milk formula [51 cases (100%)vs.71 cases (82.6%)],feeding intolerance (including GER)[17 cases (33.3%)vs.1 1 cases (12.8%)],gut infection[8 cases(15.7%)vs.4 cases(4.7%)],transfusion of blood or/and bloody prod-ucts[12 cases(23.5%)vs.1 1 cases(12.8%)]showed statistically significant differences between the aller-gy group and control group(χ2 =19.538,P =0.000;χ2 =9.989,P =0.002;χ2 =8.308,P =0.004;χ2 =4.691 ,P =0.030;χ2 =5.198,P =0.023 ).Conclusion Symptoms of CMPA in infants no more than 3 months old involve mainly digestive system such as diarrhea,bloody stool,GER.Intake of cow milk formula in neonatal period play an important role in triggering CMPA.