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 investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

Objective To explore the determination of nicotine in cigarettes by fluorescein and fluorimetry-basic possession of bonuses system.Methods Nicotine could interfere with fluorescence energy transfer between fluorimetry-basic possession of bonuses.A new way of energy transfer was established to determinate nicotine according to the fluorescence increment of fluorimetry.Results The linear range was 0.2-7.0 mg/L for the concentration of nicotine.The correlative coefficient was 0.9992.The detection limit was 0.18 mg/L.The recovery rates were 99.0 %-105 %,and RSDs were 1.1 %-4.8 % respectively.Conclusion This method is simple,fast,accurate and sensitive.It can be used to determinate nicotine in cigarettes.

Objective:To investigate the application valve of bFGF to improve the viability of subdermal vascular network flap.Methods:Four white healthy pigs were used,each pig had 6 SVNF on back,16cm?4cm,totally 24 flaps were divided randomly into 2 groups:The bFGF groups and the control groups.On postoperative day 6,we observed the appearance of the flaps.The survival area of each flap was measured and the flap was harvested for histological analysis and the density of angiogenesis was also examined.Results:On postoperative day 6,the survival rates of the bFGF group and the control group were (81.2?1.7)% and (66.2?1.8)% respectively,the angiogenesis density of the middle and the distal segment in the bFGF group was (16.7?6.0)/mm2,(29.7?5.5)/mm2,(14.9?6.0)/mm2 respectively,while (16.6?4.0)/mm2,(21.4?5.2)/mm2,(3.5?5.1)/mm2 respectively in the control group.The bFGF group was superior to the control group in the appearance and histological analysis of the flaps.Conclusion:The results suggest that the injection of bFGF locally can promote the survival rate by accelerating the blood circulation of the SVNF’ bottom and edge,shorten the division time of SVNF and broaden the ratio of length and width.

Objective To compare curative effects between posterior approach microendoscopic discectomy (MED) and traditional open discectomyin the treatment of lumbar spinal stenosis (LSS). Methods A total of 70 cases of lumbar spinal stenosis from October 2000 to December 2002 were divided into two groups: the MED Group ( n =30) and the Open Group ( n =40). Curative outcomes were compared between the two groups. Results The rate of excellent or good results was 93.3% in the MED Group (28/30) and 90.0% in the Open Group (36/40), without statistically significant difference ( ? 2 =0.819, P =0.664). The operation time was significantly shorter in the MED Group than in the Open Group ( t =2.295, P =0.025). The intraoperative blood loss was significantly less in the MED Group than in the Open Group ( t =-42.344, P =0.000). The time to normal activities in the MED Group was significantly shorter than that in the Open Group ( t =-30.123, P =0.000). Conclusions Curative effects of MED are identical with those of traditional surgery in the treatment of lumbar spinal stenosis, but shorter operation time, less blood loss and quicker postoperative recovery are achieved in MED.