Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.

Zhejiang University School of Medicine's affiliated Sir Run Run Shaw Hospital has responded to innovative rehabilitation healthcare policy by implementing enhanced recovery after surgery(ERAS)wards based on healing concepts during the development of new wards in its multi-campus integration.By integrating 5G communication technology with the hospital's various information systems and leveraging the hospital's locational advantages,the hospital has upgraded its software and hardware configurations,promoting a multidisciplinary collaborative bedside management model in the context of new technologies.In terms of overall environment construction,the hospital uses best healing theories in physical design,organizational conditions,and interpersonal relationships to facilitate and support patients'healing experiences,effectively improving medical and nursing services.