Multimorbidity of cardiometabolic disease (CMD) and cancer is a growing but understudied global challenge in an aging world. Here, we perform multistate analysis in 429,555 UK Biobank participants to investigate transition patterns, identify multiomics signatures, and construct prediction models from baseline to single and multiple morbidities. During a median follow-up of 15 years, 105,903 participants develop single morbidity and 15,088 develop multimorbidity of CMD and cancer. Participants with multimorbidity have a 13%-33% higher mortality probability than those healthy or with single morbidity. In individuals living with multimorbidity, the development of CMD before cancer presents a higher mortality risk than the reverse order. Distinct and shared multiomics signatures are identified, with proteomics scores outperforming other omics in predicting disease trajectories (ΔC-statistic vs. base model: 0.03–0.14). This study reveals distinct transition patterns in CMD-cancer multimorbidity cluster and develops potentially useful prediction tools for supporting risk management if externally validated.

Molecular glues (MGs), a class of small-molecule degraders, exhibit drug-like properties that generally conform to Lipinski's rule of five, while uniquely mediating the stabilization or induction of protein-protein interactions. By altering the surface properties of either target proteins or E3 ligases, MGs promote the formation of a ternary complex comprising the MG, an E3 ligase, and a target protein. This interaction facilitates the polyubiquitination and subsequent degradation of the target protein via the ubiquitin-proteasome system. Owing to its distinctive mechanism of action and broad therapeutic potential, MG is offering novel approaches to disease treatment. This review summarizes recent advances in MGs targeting NIMA-related kinase 7 (NEK7), WEE1, CDK2, GSPT1 and VAV1, emphasizing the rational design, benefits, and potential limitations, highlighting rational design principles, advantages, and current limitations including challenges in achieving selectivity and rational design that provide critical insights for enhancing MG efficacy. These developments are crucial for advancing the application and optimization of molecular glues targeting NEK7, WEE1, CDK2, GSPT1 and VAV1.

Background: The acute blockage in coronary arteries further causes acute coronary syndrome (ACS). There are 2 main factors implicated in the activation and aggregation of platelets. However, this present study aimed to investigate the effect of salvianolic acid A (SAA) on the platelets in patients with ACS and explore its potential mechanism of action. Methods: The impact of SAA on platelets under different stimulation conditions was studied using flow cytometry and platelet aggregation detection techniques. Results: The results demonstrated that in 40 ACS patients, ex vivo treatment of platelets with SAA (0.1 mg/ml) significantly reduced aggregation and activation. Intriguingly, we found no significant difference between the 3 types of ACS patients in the antiplatelet effect of SAA. Moreover, the results indicated that C-reactive protein, alanine aminotransferase, C-reactive protein-to-albumin ratio, total cholesterol, and low-density lipoprotein levels were negatively correlated with the anti-platelet effect of SAA in ACS patients and that a history of smoking may reduce the anti-platelet effect of SAA in the same group. Conclusion: In summary, the above findings of this study highlight the therapeutic potential of SAA against platelets in patients with ACS, providing new insights into clinical treatment and experimental research.

Background: Diabetic kidney disease, a severe diabetes microvascular complication affecting 30%~40% of diabetic patients, raises end‐stage renal disease and mortality risks. This study is aimed at developing and validate a novel index combining obesity measures and metabolic parameters to screen renal impairment in newly diagnosed T2DM patients. Methods: A total of 387 and 259 newly diagnosed T2DM patients were recruited for model development and validation, respectively. Renal impairment was defined as eGFR < 60 mL/min/1.73 m ² and/or urinary albumin‐to‐creatinine ratio (UACR) ≥ 30 mg/g. Obesity‐ or metabolism‐related indicators were collected. Significantly independent indicators were selected via bidirectional stepwise regression in the modeling patients to develop a comprehensive index termed InMOI. In the validation patients, restricted cubic spline analysis examined the dose‐response relationship between InMOI and renal impairment, whereas ROC curves assessed the screening performance. Results: The triglyceride‐glucose index (TyG) combined with various obesity measures showed significant associations with renal impairment. The InMOI, derived from TyG‐BMI and TyG‐waist to hip ratio (TyG‐WHR), demonstrated a linear dose‐response relationship with the odds ratio for renal impairment. InMOI achieved an AUC of 0.78 for identifying renal impairment. Optimizing the index by replacing WHR with the visceral‐to‐subcutaneous fat area ratio measured by DEXA, the modified InMOI (m‐InMOI) showed a better performance (AUC = 0.81). Conclusion: This study underscores the value of metabolism‐obesity indices in early detection of diabetic renal damage and highlights the pathogenic role of visceral obesity and metabolic dysregulation in diabetic kidney disease. The InMOI provides a practical tool for large‐scale screening and early prevention of diabetic kidney disease.

The anti-atherosclerotic effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are well-documented, yet the underlying molecular mechanisms, particularly via cross-organ crosstalk, remain unclear. Here, a high-fat diet-induced atherosclerosis (AS) model in ApoE^–/– mice was constructed. Compared with controls, AS mice exhibited elevated serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, along with reduced high-density lipoprotein cholesterol levels, impaired hepatic and cardiac function, enlarged aortic plaque area, and pronounced hepatic steatosis and cardiac lipid deposition. DHA/EPA intervention reversed these biochemical and histopathological abnormalities, and conferred superior hepatoprotection than Atorvastatin. Transcriptomics identified 1453 and 1663 differentially expressed genes in liver and aorta of AS mice, respectively. DHA/EPA up-regulated genes related to hepatic cholesterol metabolism and bile acid synthesis, and aortic genes encoding ABC transporters and PPAR signaling components. Conversely, they suppressed hepatic IL-17 signaling and endothelial adhesion molecules. MicroRNA quantification showed significant modulation of aortic miR-33a, miR-146a-3p, miR-155 and miR-223-3p levels, implicating regulation of lipid metabolism and inflammation. Collectively, these data indicate that DHA and EPA exert synergistic anti-atherosclerotic effects via the aorta-liver axis, regulating lipid metabolism, inflammation and vascular remodeling via a miR-30a/146a-3p/223-3p mediated network. These findings provide experimental and mechanistic supports for nutritional intervention of AS.