Publications by authors named "Liu Zhenming"

Artificial intelligence (AI) has emerged as a transformative force in healthcare, with applications spanning diagnostics to drug development. However, its integration into drug regulation remains nascent, with varying degrees of adoption and implementation across different regulatory bodies worldwide. This review aims to provide a comprehensive overview of the current state of AI in drug regulation, encapsulating AI-related policies, initiatives, and its practical application in regulatory agencies globally.

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Src homology-2-containing protein tyrosine phosphatase (PTP) 2 (SHP2) is a pivotal PTP that modulates key cellular processes including proliferation, differentiation, and migration. Its overexpression is implicated in the pathogenesis of various malignancies, highlighting the need for effective SHP2 inhibitors. Herein, we report the design and synthesis of a novel series of thiazolo[5,4-]pyridine and imidazo[1,2-]pyrimidine derivatives as SHP2 allosteric inhibitors identified through active fragment splicing.

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Lung squamous cell carcinoma (LUSC), a highly aggressive subtype of lung cancer, presents significant therapeutic challenges due to its complex molecular underpinnings. Recently, NSD3 has been identified as a key driver in the pathogenesis of LUSC, providing a new direction for targeted interventions. Herein, we report the rational design, synthesis, and comprehensive biological evaluation of a series of NSD3 inhibitors, culminating in the identification of compound A8, which demonstrates potent inhibitory activity against NSD3 and LUSC cell proliferation, with an IC of 0.

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Polo-like kinase 1 (PLK1) plays pivotal roles in cell division and cancer pathogenesis, making it a highly coveted therapeutic target for anticancer strategies. This article reports a series of PLK1 inhibitors developed using a structure-based strategy, culminating in the discovery of compound , a novel isoform-specific PLK1 inhibitor with excellent kinome selectivity. , this compound exhibited superior anticancer potency across a broad spectrum of cell lines, particularly against K562, achieving a remarkable IC value of 0.

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Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive subtype of metabolic dysfunction-associated steatotic liver disease (MASLD), has limited pharmacological treatment options. Therefore, we aimed to identify novel therapeutic targets.

Methods: The Gene Expression Omnibus (GEO) database and human liver tissues obtained from patients with MASH were used to identify differentially expressed genes in MASH.

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Unlabelled: Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral intervention.

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Bisphenol A (BPA) is a well-known endocrine-disrupting pollutant that poses significant environmental challenges globally. However, the toxicity of nitro-BPA (NBPA), the primary transformation product of BPA, remains poorly understood. This study employs a multi-omics approach, integrating in silico and bioinformatics analyses, to investigate and compare the male reproductive toxicity of BPA and NBPA in male zebrafish exposed to environmentally relevant concentrations.

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Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients.

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Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that severely diminishes the quality of life for millions. The NLRP3 inflammasome, a critical mediator of inflammation, has emerged as a promising therapeutic target for AD. In this study, we report the development and optimization of a novel series of sulfonylurea-based NLRP3 inhibitors, with a focus on compound MC1 for the treatment of AD.

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Gain-of-function (GOF) mutations of the sodium-activated potassium channel K1.1 (Slack, Slo2.2, or K4.

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This article describes prototype temperature compensated piezoelectric MEMS oscillators operating in the wide temperature range from C to C for real-time clock (RTC) applications. The AlN-on-Si resonator is centrally anchored at one point and designed for low power operation with a wide frequency tuning range of 5000 ppm. The oscillators exhibit a stable sinusoidal output at about 497-kHz frequency for time keeping applications with an integrated phase jitter (IPJ) being better than the best commercially available MEMS RTC oscillators for supplementary use in portable devices for clocking audio circuits.

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Gout as a common inflammatory arthritis seriously affects the quality of life of a large number of people. Targeting NLRP3 inflammasome has been certified as a promising therapeutic strategy for gout. This study, a series of new imidazolidinone derivatives were validated as NLRP3 inhibitors by scaffold hopping from the reported NLRP3 inhibitor CSC-6.

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Article Synopsis
  • The NLRP3 inflammasome is crucial in various hard-to-treat diseases, making it a key target for new therapies.
  • A new orally effective NLRP3 inhibitor called SN3-1 was developed using advanced deep-learning techniques, which improved the identification of potential drug candidates.
  • SN3-1 has shown strong safety and effectiveness in preclinical tests, marking it as a promising option for future NLRP3 inhibitor development.
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Hepatitis B Virus (HBV) remains a critical global health issue, with substantial morbidity and mortality. Current therapies, including interferons and nucleoside analogs, often fail to achieve complete cure or functional eradication. This review explores recent advances in anti-HBV agents, focusing on their innovative mechanisms of action.

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Plants frequently encounter adverse conditions and stress during their lives. Abscisic acid (ABA) plays a crucial role in response to salt stress, and dynamic regulation of ABA levels is essential for plant growth and stress resistance. In this study, we identified a transcription factor, OsSGL (Oryza sativa Stress tolerance and Grain Length), which acts as a negative regulator in salt stress, controlling ABA synthesis.

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The brominated azo dye (BAD) Disperse Blue (DB79) is a widespread environmental pollutant. The long-term toxicological effects of DB79 and the mechanisms thereof must be understood to allow assessment of the risks of DB79 pollution. A dual-omics approach employing in silico analysis, bioinformatics, and in vitro bioassays was used to investigate the transgenerational (F-F) toxicity of DB79 in zebrafish at environmentally relevant concentrations and identify molecular initiating events and key events associated with DB79-induced fertility disorders.

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Ferroptosis is a unique type of non-apoptotic form of cell death characterized by increased lipid hydroperoxide levels. It has relevance for a number of pathological conditions including multiple organ injuries and degenerative diseases. GPX4 plays an important role in ferroptosis by repairing lipid hydroperoxides.

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Development of resistance to therapy-induced cell death is a major hurdle in the effective treatment of advanced solid tumors. Erastin and RSL3 were originally found to induce synthetic lethality by induction of a novel form of cell death termed ferroptosis. Emerging evidence suggests that ferroptosis inducers enhance chemosensitivity of classic therapeutic agents by triggering ferroptotic cell death.

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The pandemic and tremendous impact of severe acute respiratory syndrome coronavirus 2 alert us, despite great achievements in prevention and control of infectious diseases, we still lack universal and powerful antiviral strategies to rapidly respond to the potential threat of serious infectious disease. Various highly contagious and pathogenic viruses, as well as other unknown viruses may appear or reappear in human society at any time, causing a catastrophic epidemic. Developing broad-spectrum antiviral drugs with high security and efficiency is of great significance for timely meeting public health emergency and protecting the lives and health of the people.

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Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression.

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Farnesoid X receptor (FXR) is a bile acids receptor and plays a crucial role in regulating bile acids, lipids, and glucose metabolism. Previous research suggests that inhibiting FXR activation can be beneficial in reducing cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, offering potential treatment options for metabolic syndrome with lipid disorders. Herein, we report p-acetylaminobenzene sulfonate derivatives as a novel scaffold of FXR antagonists by multistage screening.

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Article Synopsis
  • Chemical reactions are essential for organic chemistry and drug design, with data-driven approaches revolutionizing the optimization and discovery of novel reactions using AI.
  • Effective machine learning in this field requires developing strong representations and features from large reaction datasets to improve reaction performance.
  • This review explores various reaction featurization methods, discusses the strengths and weaknesses of different representation techniques like SMILES and molecular graphs, and proposes new ideas for chemical reaction pretraining.
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: Drug-likeness of a compound is an overall assessment of its potential to succeed in clinical trials, and is essential for economizing research expenditures by filtering compounds with unfavorable properties and poor development potential. To this end, a robust drug-likeness prediction method is indispensable. Various approaches, including discriminative rules, statistical models, and machine learning models, have been developed to predict drug-likeness based on physiochemical properties and structural features.

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