Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Objective:To explore the relationship between the latent classes of online emotion regulation among college students and the distribution difference of different types on variables such as gender,grade,ages of surfing the net and so on.Methods:Totally 421 college students were assessed with Online Emotion Regulation Questionnaire (OERQ).Latent class analysis was used to identify online emotion regulation classes,and then analyzed the distribution of latent classes among different genders,grades and ages of surfing the net.Results:Two latent classes of online emotion regulation were identified,including online emotion inhibiting/ignoring class (37.6％) and online emotion venting class (62.4％).The prevalence of online emotion venting class among girls (56.6％ vs.3.8％),sophomores (36.3％ vs.11.9％),juniors (23.4％ vs.3.1％),those with more than 36 months of surfing the net (31.6％ vs.18.8％) were significantly higher than the other of the respective kind.Whereas,the rate of inhibiting/ignoring class among boys (32％ vs.7.6％),freshmen (20％ vs.5％) were significantly higher.Conclusion:It suggests that online emotion regulation could be divided into two different latent classes and prevalence of each class is significantly different in different genders,grades,and ages of surfing the net.

Human cytochrome P450 (CYP) has a pivotal role on metabolism of xenobiotics and endogenous substances in clinical practice. Since the CYP from human tissue is very complex, and the human tissue itself is not easy to obtain, investigators begin to use all kinds of expression system to heterogeneously express the CYP. The single CYP expressed was then used for drug metabolism and drug-drug interaction research, to improve the efficiency of high-throughput drug screening greatly. Besides, since the polymorphism of drug-metabolizing enzymes makes efficacy variance for some drugs in different population, the heterogeneous expression and drug metabolizing research of certain CYP mutants will be helpful to guide the optimization of therapeutic regimen and conduct the personalized medication.
Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Design ; Drug Evaluation, Preclinical ; Gene Expression ; Humans

OBJECTIVETo investigate the optimal conditions of tri-expression of CYP3A4, POR and cyt b5 in Sf 9 cells.

METHODSThe Sf 9 cells expressing CYP3A4, POR and cyt b5 were cultured in shaker flasks. The optimized conditions, including the temperature and rotation speed, the culture volume, the amount of surfactant and the culture time were studied. The expressed products in microsomes were used to metabolize the testosterone and their metabolic activity was determined.

RESULTSWhen the temperature and rotation speed of the shaker were 27 degree and 90 r/min, the cell density and culture volume were 5X105 cells/ml and 80-120 ml per 250 ml shaker flasks, respectively. When Pluronic F-68 was 0.1% and the culture time was 72 h, the condition was most suitable for culture of Sf 9 cells and expression of targeted proteins. When the ratio of the volume of three added viruses was 1:1:1, the expression condition was optimal, under which the Km, Vmax, and CLint for testosterone metabolism were 119.6 μmol/L,0.52 μmol/(min*g protein) and 4.34 ml/(min*g protein), respectively.

CONCLUSIONThe conditions of tri-expressing of CYP3A4, POR and cyt b5 have been optimized in the study and the product CYP3A4 is obtained with higher metabolic activity.

Animals ; Cytochrome P-450 CYP3A ; biosynthesis ; Cytochromes b5 ; biosynthesis ; Humans ; Insecta ; NADPH-Ferrihemoprotein Reductase ; biosynthesis ; Sf9 Cells