Wee1-like protein kinase 2 (WEE2) is an oocyte-specific kinase that regulates meiotic arrest and fertilization. Its largely restricted expression in female germ cells and absence in somatic tissues make it a highly selective target for reproductive health interventions. Despite its central role in human fertility, no clinically approved WEE2 modulator is available. In this study, we employed an integrated in silico approach that combines structure-based virtual screening, molecular dynamics (MD) simulations, and MM-PBSA free-energy calculations to identify repurposed drug candidates with potential WEE2 inhibitory activity. Screening of ~3800 DrugBank compounds against the WEE2 catalytic domain yielded ten high-affinity hits, from which Midostaurin and Nilotinib emerged as the most mechanistically relevant based on kinase-targeting properties and pharmacological profiles. Docking analyses revealed strong binding affinities (−11.5 and −11.3 kcal/mol) and interaction fingerprints highly similar to the reference inhibitor MK1775, including key contacts with hinge-region residues Val220, Tyr291, and Cys292. All-atom MD simulations for 300 ns demonstrated that both compounds induce stable protein–ligand complexes with minimal conformational drift, decreased residual flexibility, preserved compactness, and stable intramolecular hydrogen-bond networks. Principal component and free-energy landscape analyses further indicate restricted conformational sampling of WEE2 upon ligand binding, supporting ligand-induced stabilization of the catalytic domain. MM-PBSA calculations confirmed favorable binding free energies for Midostaurin (−18.78 ± 2.23 kJ/mol) and Nilotinib (−17.47 ± 2.95 kJ/mol), exceeding that of MK1775. To increase the translational prioritization of candidate hits, we place our structure-based pipeline in the context of modern machine learning (ML) and deep learning (DL)-enabled virtual screening workflows. ML/DL rescoring and graph-based molecular property predictors can rapidly re-rank docking hits and estimate absorption, distribution, metabolism, excretion, and toxicity (ADMET) liabilities before in vitro evaluation.

Diffuse large B-cell lymphoma (DLBCL), the most prevalent aggressive non-Hodgkin lymphoma, exhibits substantial molecular heterogeneity and arises from germinal center or post-germinal center B cells through recurrent genetic and epigenetic dysregulation of critical signaling pathways. Aberrations involving BCL6, MYC, MYD88, and components of B cell receptor and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B) signaling play central roles in lymphomagenesis, treatment resistance, and clinical outcomes. Gene expression profiling has defined major molecular subgroups in DLBCL, including germinal center B cell–like and activated B cell–like tumors, that show distinct pathogenesis and prognosis. High-risk entities, such as double- and triple-hit lymphomas, remain therapeutically challenging despite advances in immunochemotherapy. Recent progress in molecular diagnostics and targeted therapies, including immune checkpoint inhibition, Bruton tyrosine kinase inhibitors, B-cell lymphoma 2 (BCL2) antagonists, and Chimeric antigen receptor-T cells, has expanded precision-based treatment strategies. This review summarizes advances in understanding the molecular mechanisms of DLBCL and emphasizes emerging therapeutic approaches informed by genomic and microenvironmental discoveries.

Al Qurayyat salt is a traditional salt product that has been historically used in northern Saudi Arabia for food preservation, seasoning, and domestic uses. The city of Al Qurayyat is famous for its salt and is known as the city of salt in Saudi Arabia due to the abundance of salt deposits in areas such as Etra and Kaf. Despite its daily use by locals, there is no scientific information available regarding its chemical composition, heavy metals and safety. In this preliminary study, we aimed to analyze the physicochemical properties and metal contents of Al Qurayyat salt (ETR) and compare it to a commercially known salt (SAS). ETR chemical analysis showed a purity of 98.179%, moisture content of 0.68%, insoluble matter of 0.25%, and sulphate concentration of 7400 mg/kg. As expected, Iodine was not detected in the ETR sample, suggesting that the salt is non-iodized. Mineral analysis showed the presence of calcium (27 mg/kg), magnesium (32 mg/kg), potassium (10 mg/kg), copper (0.21 mg/kg), mercury (0.03 mg/kg), lead (0.13 mg/kg), and arsenic (0.01 mg/kg), while cadmium and iron were not detected or below the limit of detection. Heavy metal concentrations was below commonly accepted safety limits for edible salts. These findings provide the first reported physicochemical characterization of Al Qurayyat salt and establish baseline data for future investigations regarding its mineral composition, potential health uses, safety, nutritional significance, and potential industrial or culinary applications.

Objectives: Disulfidptosis is a recently defined form of regulated cell death driven by aberrant disulfide bonding in actin cytoskeleton proteins during glucose starvation and high cystine import. To our knowledge, its relevance in mantle cell lymphoma (MCL), a clinically heterogeneous B-cell malignancy, has not been examined. Methods: Using publicly available microarray data (GSE93291; 123 MCL patients with overall survival, Affymetrix GPL570), we characterized 13 canonical disulfidptosis-related genes (DRGs). A six-gene LASSO-Cox score was constructed, evaluated by Kaplan–Meier analysis and time-dependent ROC, internally validated by bootstrap optimism correction, and tested for independence from a proliferation score in a multivariable model. Results: Seven DRGs were individually prognostic; notably, SLC7A11 , the cystine transporter central to disulfidptosis, was not (hazard ratio [HR] = 1.14; p=0.36), whereas cytoskeletal genes carried the signal. The six-gene score ( SLC3A2 , MYH9 , MYH10 , FLNB , MYL6 , DSTN ) separated two groups with markedly different survival (HR=4.28; 95 % CI=2.38–7.70; log-rank p=1.8 × 10 ⁻⁷ ). Discrimination held after bootstrap correction (apparent C-index, 0.76; corrected, 0.72). The score was uncorrelated with proliferation (r=0.14) and remained prognostic after adjustment (likelihood-ratio p=3.9 × 10 ⁻¹² ). Conclusions: To our knowledge, this is the first description of disulfidptosis-related gene expression in MCL, suggesting the prognostic signal is cytoskeletal rather than transporter-driven and distinct from proliferation. As no independent public MCL cohort with survival was available, external validation could not be performed and remains an essential next step.