Hemophilia

A novel framework for the discovery of MAPK-activated protein kinase 2 (MAPKAPK2) inhibitors using a multi-feature deep learning ensemble.

MAPKAPK2 is a promising therapeutic target in numerous diseases. However, many MAPKAPK2 inhibitors are plagued by low solubility and permeability, and none have advanced through clinical trials. New computational methods utilizing deep learning can speed up inhibitor identification. This study aims to develop and validate a novel framework for MAPKAPK2 inhibitor discovery utilizing an ensemble of ...

Combating New Delhi metallo-beta-lactamase-1 (NDM-1): an integrated review of inhibitor development and next-generation therapeutic platforms.

New Delhi metallo-β-lactamase-1 (NDM-1), which has emerged globally, exhibits resistance to almost all β-lactam antibiotics, including carbapenems, posing a major challenge to modern antibiotic therapy. Deep sequencing has revealed the evolution of several new NDM variants (some of the variants are more thermostable than NDM-1) due to mutations that increase their zinc-binding and catalytic effici...

Integrating machine learning and deep learning with multiple molecular fingerprints for topoisomerase I inhibitor screening and lead identification.

Topoisomerase I (TOP1) is a crucial anticancer target, but the development of traditional TOP1 inhibitors suffers from long research cycles, high cost...

Revealing Airflow-Particle Dynamics in Dry Powder Inhalers.

Dry powder inhalers (DPIs) are essential for pulmonary drug delivery, yet how adhesive formulation powders are converted into well-dispersed aerosols ...

From dysbiosis to precision oncology: translational role of the microbiome in gastrointestinal cancer.

Gastrointestinal (GI) cancers, including colorectal, gastric, pancreatic, hepatocellular, and esophageal malignancies, remain a leading cause of cance...

Integrating Target Prediction and Transcriptomic Analysis Identifies the AKR1C2-KRT8 Axis in Rotenone-Induced Dopaminergic Neuron Injury.

Parkinson's disease (PD) is a complex neurodegenerative disorder in which environmental toxins play a critical etiological role. Rotenone, a classical...

Pharmacological personalization of JAK inhibitors in rheumatoid arthritis: A multi-omics and AI-based scoping review and evidence-gap map.

INTRODUCTION: Personalization of Janus kinase inhibitor (JAKi) therapy in rheumatoid arthritis (RA) remains an unresolved clinical task. Multi-omics/m...

Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) progression is driven by the pathogenic transformation of stromal fibroblast-like synoviocytes (FLSs). Using artificial inte...

[Advances and prospects of hemostatic strategies in hepatic surgery].

The liver is characterized by abundant blood supply and intricate anatomical architecture,rendering intraoperative and postoperative hemorrhage a prim...

Dockformer: A Transformer-Based Molecular Docking Paradigm for Large-Scale Virtual Screening.

Molecular docking is a critical step in drug development, enabling the virtual screening of compound libraries to identify potential ligands for speci...

Machine learning-driven drug repurposing and computational validation for Nipah virus.

The recurring Nipah virus outbreaks and the lack of effective antiviral therapies, emphasize the urgent need for effective therapeutic interventions. ...

Identification of novel serotonin transporter (SERT) inhibitors via large-scale machine learning-based virtual screening and molecular dynamics simulations.

The serotonin transporter (SERT) plays a pivotal role in inflammatory responses and is a central therapeutic target for depression. Consequently, iden...

De Novo Molecular Design and Bioactivity Prediction of Novel Hexahydroquinolines as Plasmodium falciparum Calcium-Dependent Protein Kinase 4 (CDPK4) Inhibitors.

Plasmodium falciparum Calcium-Dependent Protein Kinase 4 (PfCDPK4) is a validated target for malaria transmission-blocking interventions, as its inhib...

Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.

BACKGROUND: Lung neuroendocrine tumours (NETs, also known as carcinoids) are rapidly rising in incidence worldwide but have unknown aetiology and limi...

Biomarkers in facioscapulohumeral muscular dystrophy.

PURPOSE OF REVIEW: Facioscapulohumeral muscular dystrophy is one of the most frequent myopathies. Its clinical presentation and genetic background are...

Integrative single-cell and machine-learning analysis identifies LGALS1 as a macrophage-associated diagnostic and prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by marked heterogeneity and an immunosuppressive microenvironment in which tumor-associate...

AI-augmented discovery of autophagy regulators through mechanistic interpretation of multiomics data.

Yu Xue: [email protected] Large-scale multiomics profiling has delineated dynamic molecular landscapes during autophagy, yet translating these complex...

Machine learning of sunitinib resistance genes reveals that SP5 regulates angiogenesis and sunitinib resistance in RCC via the VEGFA/AKT axis.

BACKGROUND: Sunitinib resistance remains a major clinical challenge in renal cell carcinoma, and the underlying molecular mechanisms are incompletely ...

Machine Learning-Based Screening of Optimal miRNA Targets Enabled by a Cytosolic Delivery Carrier for Augmenting Cancer Therapy.

Nucleic acid therapeutics offer promise for precision cancer treatment, but are limited by inaccurate target selection and inefficient delivery. This ...

Targeting FAR1 to inhibit intestinal macrophage ferroptosis: repurposing irinotecan as a novel sepsis therapy.

Intestinal barrier breakdown is a key driver of sepsis-related multiple organ dysfunction; however, the metabolic mechanisms underlying this process r...