Nontargeted Metabolomics Revealed Novel Association Between Serum Metabolites and Incident Acute Coronary Syndrome: A Mendelian Randomization Study

Background This study was performed to identify metabolites associated with incident acute coronary syndrome (ACS) and explore causality of the associations. Methods and Results We performed nontargeted metabolomics in a nested case‐control study in the Dongfeng‐Tongji cohort, including 500 incident ACS cases and 500 age‐ and sex‐matched controls. Three metabolites, including a novel one (aspartylphenylalanine), and 1,5‐anhydro‐d‐glucitol (1,5‐AG) and tetracosanoic acid, were identified as associated with ACS risk, among which aspartylphenylalanine is a degradation product of the gut‐brain peptide cholecystokinin‐8 rather than angiotensin by the angiotensin‐converting enzyme (odds ratio [OR] per SD increase [95% CI], 1.29 [1.13–1.48]; false discovery rate–adjusted P=0.025), 1,5‐AG is a marker of short‐term glycemic excursions (OR per SD increase [95% CI], 0.75 [0.64–to 0.87]; false discovery rate–adjusted P=0.025), and tetracosanoic acid is a very‐long‐chain saturated fatty acid (OR per SD increase [95% CI], 1.26 [1.10–1.45]; false discovery rate–adjusted P=0.091). Similar associations of 1,5‐AG (OR per SD increase [95% CI], 0.77 [0.61–0.97]) and tetracosanoic acid (OR per SD increase [95% CI], 1.32 [1.06–1.67]) with coronary artery disease risk were observed in a subsample from an independent cohort (152 and 96 incident cases, respectively). Associations of aspartylphenylalanine and tetracosanoic acid were independent of traditional cardiovascular risk factors (P‐trend=0.015 and 0.034, respectively). Furthermore, the association of aspartylphenylalanine was mediated by 13.92% from hypertension and 27.39% from dyslipidemia (P<0.05), supported by its causal links with hypertension (P<0.05) and hypertriglyceridemia (P=0.077) in Mendelian randomization analysis. The association of 1,5‐AG with ACS risk was 37.99% mediated from fasting glucose, and genetically predicted 1,5‐AG level was negatively associated with ACS risk (OR per SD increase [95% CI], 0.57 [0.33–0.96], P=0.036), yet the association was nonsignificant when further adjusting for fasting glucose. Conclusions These findings highlighted novel angiotensin‐independent involvement of the angiotensin‐converting enzyme in ACS cause, and the importance of glycemic excursions and very‐long‐chain saturated fatty acid metabolism

Strain Modulation for Light‐Stable n–i–p Perovskite/Silicon Tandem Solar Cells

Perovskite/silicon tandem solar cells are promising to penetrate photovoltaicmarket. However, the wide-bandgap perovskite absorbers used in top-celloften suffer severe phase segregation under illumination, which restricts theoperation lifetime of tandem solar cells. Here, a strain modulation strategyto fabricate light-stable perovskite/silicon tandem solar cells is reported. Byemploying adenosine triphosphate, the residual tensile strain in the wide-bandgapperovskite absorber is successfully converted to compressive strain,which mitigates light-induced ion migration and phase segregation. Basedon the wide-bandgap perovskite with compressive strain, single-junctionsolar cells with the n–i–p layout yield a power conversion efficiency (PCE) of20.53% with the smallest voltage deficits of 440 mV. These cells also maintain83.60% of initial PCE after 2500 h operation at the maximum power point.Finally, these top cells are integrated with silicon bottom cells in a monolithictandem device, which achieves a PCE of 26.95% and improved light stabilityat open-circuit