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.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

In recent years, adaptive laboratory evolution (ALE) has emerged as a powerful tool for basic research in microbiology (e.g., molecular mechanisms of microbial evolution) and efforts on evolutionary engineering of microbial strains (e.g., accelerated evolution of industrial strains by bringing beneficial mutations). The ongoing rapid development of next-generation sequencing platforms has provided novel insights into growth kinetics and metabolism of microbes, and thus led to great advances of this technique. In this review, we summarize recent advances in the applications of long-term and short-term ALE techniques mainly for microbial strain engineering, and different modes of ALE are also introduced. Furthermore, we discuss the current limitations of ALE and potential solutions. We believe that the information reviewed here will make a significant contribution to further advancement of ALE.
High-Throughput Nucleotide Sequencing ; Laboratories ; Mutation

OBJECTIVE：To explore the mode of pharmaceutical care for oral medication of tumor patients with dysphagia by clinical pharmacists ，so as to promote clinical rational and safe drug use. METHODS ：Based on typical cases ，the problems existing in the oral medication of tumor patients with dysphagia were analyzed ，and the medication guidance and pharmaceutical care given by clinical pharmacists were expounded. RESULTS ：Clinical pharmacists found that tumor patients with dysphagia had some problems during oral medication ，such as improper administration position ，tube feeding of slow-controlled release preparations after opening the capsule ，limited administration route ，biting cytotoxic drugs ，unknown solubility of targeted drugs ，interaction of multiple drugs. In view of the above problems ，clinical pharmacists assisted physicians and nursing staff to provide pharmaceutical care to patients in combination with the patient ’s disease characteristics ，pharmacy，pharmacokinetics，pharmacodynamics，drug solubility，drug interaction and other factors ，such as skillfully using appropriate drug delivery location and mode ，using local drug delivery mode ，selecting appropriate dosage form based on pharmaceutical knowledge （the characteristics of new dosage form ）， guiding patients to use drugs correctly by being familiar with the characteristics of cytotoxic drugs and targeted drugs ，paying attention to potential drug interactions and guiding nurses to use drugs correctly. The situation of improper medication was improved. CONCLUSIONS ：Clinical pharmacists should participate in clinical therapy actively ，and make appropriate interventions with professional knowledge of pharmacy so as to promote the correct use of oral medication for tumor patients with dysphagia.

Electron Spin Resonance Spectroscopy ; Glycerol ; chemistry ; Mesylates ; chemistry ; Muramidase ; chemistry ; Protein Structure, Tertiary ; Proteins ; chemistry ; Spin Labels ; Temperature ; Viscosity

OBJECTIVETo study the anti-tumor effects of combined IL-12 and granalocyte-macrophage-colong scimulating factor (GM-CSF) gene therapy on murine hepatocellular carcinoma.

METHODSTwenty-four mice received subcutaneous inoculation of 1 x 10(6) BNL hepatoma cells were randomly divided into the following four groups with different cytokine encoding plasmids (6 mice for each group): (1)pXX-GM-CSF 12.5 microg and pXX-IL-12 12.5 microg; (2)pXX-IL-12 25 microg; (3)pXX-GM-CSF 25 microg; (4)pXX-Neo 25 microg. The plasmids were given through tail vein using a versatile hydrodynamics-based DNA delivery method on day 3 and day 6 after tumor challenge. The growth of tumor and cellular immune response were observed intensively. The changes in serum concentration of IL-12, GM-CSF, and IFN-gamma after plasmids injection were also observed.

RESULTSCo-delivery of IL-12 and GM-CSF could mount stronger anti-tumor effects, longer term enhanced IL-12 expression and lower level of IFN-gamma than did IL-12 alone.

CONCLUSIONSCombined IL-12 and GM-CSF can render a strong anti-tumor effect as well as a potential to lower the side effects.

Animals ; CD4-Positive T-Lymphocytes ; cytology ; CD8-Positive T-Lymphocytes ; cytology ; Cell Division ; genetics ; physiology ; Genetic Therapy ; methods ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; genetics ; physiology ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; genetics ; physiology ; Liver Neoplasms, Experimental ; genetics ; therapy ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Plasmids ; administration & dosage ; genetics ; Time Factors ; Tumor Cells, Cultured