Qiuxia Li

OBJECTIVES: The human beta(1)-adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that beta(1)-adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension. METHODS: beta(1)-Adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay for 223 patients with essential hypertension. Sixty-one patients with certain beta(1)-adrenergic receptor diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19 for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected from those 61 for measurement of the antihypertensive effect of metoprolol. Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and blood pressure were measured weekly for the duration of metoprolol therapy. RESULTS: The descent of systolic blood pressure after metoprolol administration was significantly different among genotype groups (10.4% +/- 4.0%, 2.8% +/- 4.7%, and 1.1% +/- 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively; P < .001). We also found a similar difference in changes of diastolic blood pressure (6.1% +/- 4.3%, 2.2% +/- 4.2%, and 0.9% +/- 4.0%, respectively; P < .001) and mean arterial pressure (8.1% +/- 3.5%, 2.5% +/- 3.0%, and 1.0% +/- 2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients. Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect of metoprolol. Systolic blood pressure decreased significantly in Ser49 homozygous patients compared with Ser49Gly patients (8.4% +/- 3.2% versus 5.3% +/- 5.2%, P = .047). There was a highly significant relationship between diplotype and blood pressure during treatment. Systolic blood pressure significantly decreased in 49Ser389Arg/49Ser389Arg (12.0% +/- 3.8%, P < .001) and 49Ser389Arg/49Gly389Arg (8.4% +/- 5.5%, P < .001) patients, with the decrease in the former being more pronounced (P = .023). We also found a significant decrease in diastolic blood pressure (6.5% +/- 4.7% versus 5.7% +/- 3.2%, respectively; both P < .001) and mean arterial pressure (8.8% +/- 3.2% versus 6.9% +/- 3.7%, respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients (all P > .05). CONCLUSIONS: beta(1)-Adrenergic receptor polymorphism was associated with different blood pressure responses to metoprolol therapy in patients with essential hypertension. 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy; 49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol antihypertensive therapy.

Finding highly efficient electrocatalysts for the CO2 electroreduction reactions (CO2RR) that have high selectivity and appreciable current density to meet commercial application standards remains a challenge. Because their reduction potentials are similar to that of the associated competitive hydrogen evolution reaction and the CO2 activation kinetics are sluggish. Although single-atom catalysts (SACs) with high atom efficiency are one class of promising candidates for the CO2RR to produce CO, single-atom active sites supported on microporous carbons are not fully exposed to substrates and thus lead to low current density. Carbon aerogels with interconnected channels and macropores can facilitate mass transport. But few reports describe utilizing them as supports to anchor SACs for efficient electrocatalysis. Herein, N-doped carbon aerogels supporting Ni single atomic catalyst sites (denoted as Ni-NCA-X, X ​= ​10, 20) were fabricated by pyrolyzing Ni/Zn bimetallic zeolitic imidazolate framework (Ni/Zn-ZIF-8)/carboxymethylcellulose composite gels. Owing to abundant hierarchical micro-, meso-, and macropores and high CO2 adsorption, the Ni single active sites in the optimal Ni-NCA-10 were readily accessible for the electrolyte and CO2 molecules and thus achieved an industrial-level CO partial current density of 226 ​mA ​cm−2, a high CO Faradaic efficiency of 95.6% at −1.0 ​V vs. the reversible hydrogen electrode, and a large turnover frequency of 271810 h−1 in a flow-cell reactor at −1.0 ​V. Such excellent CO2RR performance makes Ni-NCA-10 a rare state-of-the-art electrocatalyst for CO2-to-CO conversion. This work provides an effective strategy for designing highly efficient electrocatalysts toward the CO2RR to achieve industrial current density via anchoring single-atom sites on carbon aerogels.

Gut microbiota promotes atherosclerosis, and vascular endothelial dysfunction, signalled by impaired endothelium-dependent vasorelaxation, is an early marker of atherosclerosis. Here we show that vascular microRNA-204 (miR-204) expression is remotely regulated by the microbiome, and impairs endothelial function by targeting the Sirtuin1 lysine deacetylase (Sirt1). MiR-204 is downregulated, while Sirt1 is upregulated, in aortas of germ-free mice. Suppression of gut microbiome with broad-spectrum antibiotics decreases miR-204, increases Sirt1 and bioavailable vascular nitric oxide, and improves endothelium-dependent vasorelaxation in mouse aortas. Antibiotics curtail aortic miR-204 upregulation, and rescue decline of aortic Sirt1 and endothelium-dependent vasorelaxation, triggered by high-fat diet feeding. Improvement of endothelium-dependent vasorelaxation by antibiotics is lost in mice lacking endothelial Sirt1. Systemic antagonism of miR-204 rescues impaired endothelium-dependent vasorelaxation and vascular Sirt1, and decreases vascular inflammation induced by high-fat diet. These findings reveal a gut microbe-vascular microRNA-Sirtuin1 nexus that leads to endothelial dysfunction.