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Biomedical subjects

Yueyue Wang

Publications and source records attributed to Yueyue Wang.

2 recordsLinked to original sources

Effects of intensive blood pressure control on cardio-kidney outcomes by KDIGO risk categories: a Post Hoc analysis of ACCORD-BP and SPRINT trials.

The effects of intensive systolic blood pressure (SBP) control on cardiovascular (CV) and kidney outcomes across different Kidney Disease Improving Global Outcomes (KDIGO) risk categories remain unclear. We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) and the SPRINT-eligible Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial. Participants were categorized into low, moderate, and high/very-high KDIGO risk groups. The primary outcomes were composite adverse CV events (defined as nonfatal myocardial infarction (MI), nonfatal stroke, fatal or hospitalized heart failure (HF), and CV mortality) and composite adverse kidney events (defined as a sustained decline in eGFR of &#x2265;&#xa0;40% and end-stage kidney disease (ESKD)). We found that intensive BP control reduced the risk of composite CV events (HR 0.68; 95% CI 0.59-0.78), with attenuated benefits in higher KDIGO risk categories (P for interaction = 0.055). This interaction was mainly driven by nonfatal MI and fatal or hospitalized HF (both P for interaction < 0.05). Intensive BP control increased the risk of composite kidney events (HR 1.88; 95% CI 1.52-2.33), mainly in low- and moderate-risk groups rather than in high/very-high risk groups (P for interaction = 0.04). Similar patterns were observed for sustained eGFR decline (P for interaction = 0.03), but not for ESKD (HR 1.05; 95% CI 0.74-1.48; P for interaction = 0.71). The KDIGO risk classification modified the effects of intensive BP control. Balancing CV benefits against potential kidney impacts in patients with different KDIGO risks during intensive BP treatment is recommended. Trial Registration: ClinicalTrials.gov Identifiers: NCT01206062 (SPRINT) and NCT00000620 (ACCORD).

Cardiovascular outcome

Identification of a Nonribosomal Peptide Analog With Activity Against Multiple Gram-Positive Bacteria via a Synthetic Bioinformatic Natural Product Discovery Approach.

Nonribosomal peptide (NRP) antibiotics exhibit potent biological activities and are broadly used in clinical therapy. Because most microorganisms are difficult to culture and many antibiotic biosynthetic genes are silent, traditional activity tracking approaches face major limitations in the discovery of novel NRPs. Here, based on a synthetic bioinformatic natural product (syn-BNP) discovery approach that integrates bioinformatics and chemical synthesis, a novel nonribosomal peptide synthetase (NRPS) gene cluster from the genome of Rhodococcus erythropolis D-1 was mined. A putative NRP scaffold synthesized by the NRPS encoded by this cluster was predicted. Through chemical synthesis and four rounds of structure-activity relationship (SAR) studies, 37 NRP analogs were ultimately generated. Among these analogs, ZURJC28 shows activity against multiple Gram-positive bacteria, including two drug-resistant strains. Mechanistic studies and metabolomics analyses revealed that ZURJC28 exerts membrane-disruptive activity associated with interaction with phosphatidylglycerol (PG)-enriched Gram-positive membranes, leading to membrane damage and widespread metabolic dysregulation. ZURJC28 also shows low cytotoxicity and low hemolytic activity, suggesting its preliminary in vitro safety profile.

Gram-Positive Bacteria