Shenyang Pharmaceutical University

The safety and efficacy of aspirin combined with ticagrelor or clopidogrel remain unclear in ST-segment elevation myocardial infarction (STEMI) patients with Diabetes mellitus (DM) and poor glycemic control. This study aims to assess the efficacy and safety of ticagrelor versus clopidogrel-based dual antiplatelet therapy in STEMI patients with DM and poor glycemic control undergoing pPCI. We evaluated 2732 STEMI patients with DM and poor glycemic control who underwent primary percutaneous coronary intervention (pPCI) and were registered in the "Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS)" program between November 2014 and December 2019. Using propensity score matching (PSM) and cox proportional hazards regression, we compared the in-hospital risk of major adverse cardiovascular events (MACCE), TIMI bleeding events, and net adverse clinical events (NACE) between patients receiving aspirin combined with either ticagrelor or clopidogrel. After PSM, the risk of in-hospital MACCE (HR = 0.545, 95% CI: 0.321-0.926, p = 0.025), Cardiac death (HR = 0.380, 95% CI: 0.149-0.971, p = 0.043) and NACE (HR = 0.728, 95% CI: 0.560-0.947, p = 0.018) was significantly lower in the ticagrelor group compared with the clopidogrel group (p < 0.05), while no significant difference was observed in the incidence of TIMI-bleeding events between the two groups (p > 0.05). Among STEMI patients with DM and poor glycemic control undergoing pPCI, ticagrelor use was associated with a low rate of MACCE, without an excessive risk of bleeding. The information of clinical trial registration for CCC-ACS project can be found at http://clinicaltrials.gov/study/NCT02306616.

The immunosuppressive tumor microenvironment and poor drug targeting remain major obstacles in bladder cancer (BC) therapy. To address this, a combination strategy integrating chemotherapy and immunotherapy was employed by co-delivering epirubicin (EPI) and the immune modulator imiquimod (IMQ) using a folate-modified nanocarrier. A hydroxyethyl starch-based epirubicin prodrug modified with folic acid (FA-HES-EPI) was first synthesized to improve tumor selectivity. FA-HES-EPI/IMQ micelles were then fabricated via nanoprecipitation by encapsulating IMQ into the hydrophobic core, aiming to achieve synergistic therapeutic efficacy. Folate modification conferred tumor-targeting capability to the micelles and promoted efficient cellular uptake via folate receptor-mediated endocytosis. The acid-sensitive hydrazone bond enabled controlled release of both EPI and IMQ in the acidic tumor microenvironment, thereby enhancing their combined chemo-immunotherapeutic effects. In an orthotopic BC model, FA-HES-EPI/IMQ micelles significantly enhanced drug accumulation at the tumor site, repolarized M2-type tumor-associated macrophages (TAMs) toward the M1 phenotype, remodeled the tumor stroma, and achieved a tumor inhibition rate of 96.7%, markedly surpassing that of FA-HES-EPI micelles (86.6%) and free EPI (62.3%), with negligible systemic toxicity. This pH-responsive co-delivery system represents a promising approach to improve both efficacy and safety in bladder cancer treatment.

Plutella xylostella larvae constitute the most destructive pest of cruciferous crops globally and have caused huge economic losses. However, chemical pesticides for their control are toxic to the ecological environment and there is pest resistance against them. Searching for compounds with insecticidal activity that are environmentally friendly has become imperative. Crude extracts of Streptomyces huasconensis NA10 showed significant insecticidal activities against P. xylostella larvae, and genomic mining was used to predict that this bacterial strain could produce potentially undescribed insecticidal compounds. To discover new natural biopesticides, three new compounds, azaspiromycin, pentalenolactone J and neopentalenolactone G, along with one known compound, pentalenolactone O, were isolated from marine-derived S. huasconensis NA10, guided by insecticidal activity screening. Their structures were identified through comprehensive spectroscopic data analysis and quantum chemical calculations. Remarkably, azaspiromycin contains a unique spiro-tetrahydropyran-γ-lactam bicyclic skeleton, previously unreported in natural products. Furthermore, plausible biosynthetic pathways of four compounds were deduced. In the insecticidal activity assay, these compounds showed moderate-to-strong insecticidal effects [median lethal dose (LD50) = 5.1-25.5 μm]. Among them, azaspiromycin and pentalenolactone O demonstrated significant insecticidal effects (LD50 = 8.3 and 5.1 μm), comparable to the positive control abamectin (LD50 = 4.2 μm). The result of acute toxicity further indicated that these compounds were safe for a nontarget organism (silkworm). This is the first report on the insecticidal efficacy of azaspiromycin and pentalenolactone derivatives against P. xylostella larvae. This study demonstrates the potential of azaspiromycin and pentalenolactone derivatives as novel biopesticides for effective P. xylostella control. © 2026 Society of Chemical Industry.