Evaluating a river's ecological health: A multidimensional approach.

Evaluating the health of river surface water is essential, as rivers support significant biological resources and serve as vital drinking water sources. While the Water Quality Index (WQI) is commonly employed to evaluate surface water quality, it fails to consider biodiversity and does not fully capture the ecological health of rivers. Here we show a comprehensive assessment of the ecological health of surface water in the lower Yangtze River (LYR), integrating chemical and biological metrics.

Occurrence and risk assessment of azole fungicides during the urban water cycle: A year-long study along the Yangtze River, China.

Azole fungicides (AFs) play an important role in the prevention and treatment of fungal diseases in agricultural crops. However, limited studies are addressing the fate and ecological risk of AFs in the urban water cycle at a large watershed scale. To address this gap, we investigated the spatiotemporal distribution and ecological risk of twenty AFs in the lower reaches of the Yangtze River across four seasons.

Testosterone Deficiency Promotes Hypercholesteremia and Attenuates Cholesterol Liver Uptake via AR/PCSK9/LDLR Pathways.

Background: Testosterone deficiency is reportedly correlated with an elevation of cholesterol in plasma, but the mechanism remains unclear. Our objective was to investigate the effects of testosterone deficiency on cholesterol metabolism and the corresponding molecular changes in vivo and in vitro.

Methods: SD rats were randomized into three groups: sham-operated (SHAM), subtotal orchiectomized (SO), and orchiectomized (ORX) and fed for 8 weeks.

Design and structural optimization of novel 2H-benzo[h]chromene derivatives that target AcrB and reverse bacterial multidrug resistance.

Drug efflux pumps have emerged as a new drug targets for the treatment of bacterial infections in view of its critical role in promoting multidrug resistance. Herein, novel chromanone and 2H-benzo[h]chromene derivatives were designed by means of integrated molecular design and structure-based pharmacophore modeling in an attempt to identify improved efflux pump inhibitors that target Escherichia coli AcrB. The compounds were tested for their efflux inhibitory activity, ability to inhibit efflux, and the effect on bacterial outer and inner membranes.

Design and synthesis of novel 4-substituted quinazoline-2-carboxamide derivatives targeting AcrB to reverse the bacterial multidrug resistance.

Novel 4-substituted quinazoline-2-carboxamide derivatives targeting AcrB were designed, synthesized and evaluated for their biological activity as AcrB inhibitors. In particular, the ability of the compounds to potentiate the activity of antibiotics, to inhibit Nile Red efflux and to target AcrB was investigated. In this study, 19 compounds were identified to reduce the MIC values of at least one tested antibacterial by 2- to 16-fold at a lower concentration.

Lower eGFR is associated with increased probability of liver fibrosis in Chinese diabetic patients.

Background: Kidney dysfunction is linked to nonalcoholic fatty liver disease (NAFLD) progression including fibrosis, steatosis, or inflammation. We aimed to explore whether lower levels of estimated glomerular filtration rate (eGFR) was associated with increased probability of liver fibrosis.

Methods: Two thousand six hundred eighty-nine subjects enrolled from Shanghai, China, were included in this study.

Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance.

A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux.

Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators.

Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S.

Recent Advances in the Discovery of Novel Peptide Inhibitors Targeting 26S Proteasome.

Background: The 26S proteasome is a proteolytic complex of multimeric protease, which operates at the executive end of the Ubiquitin-Proteasome System (UPS) and degrades the polyubiquitylated proteins.

Methods: After a brief introduction of 26S proteasome and Ubiquitin-Proteasome System (UPS), this review focuses on the structure and function of the 26S proteasome in intracellular protein level regulation. Then, physiological regulation mechanisms and processes are elaborated.