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Drugs that treat chronic obstructive pulmonary disease by antagonizing the M3 muscarinic acetylcholine receptor (M3R) have had a significant effect on health, but can suffer from their lack of selectivity against the M2R subtype, which modulates heart rate. Beginning with the crystal structures of M2R and M3R, we exploited a single amino acid difference in their orthosteric binding pockets using molecular docking and structure-based design. The resulting M3R antagonists had up to 100-fold selectivity over M2R in affinity and over 1,000-fold selectivity in vivo. The crystal structure of the M3R-selective antagonist in complex with M3R corresponded closely to the docking-predicted geometry, providing a template for further optimization.

Aim Methods Results Conclusion The purpose of this retrospective patient chart review was to analyze the clinical data of 52 patients with benign parotid tumors who underwent modified buried vertical mattress sutures and to assess the postoperative complication rate and patient scarring.A total of 52 patients with benign parotid tumors underwent total parotidectomy and modified buried vertical mattress suture. Variables included general characteristics (age, gender, tumor diameter, and pathologic type), surgical indicators (suture time, wound healing time, operative time, hospital stay, bleeding volume, and drainage volume), complication rates, and Sunnybrook facial neurological function score, visual scar scale (VSS) score and patient and observer scar assessment scale (POSAS) score.Most tumors were less than 3 cm in diameter, with pleomorphic adenomas being the most common. Suture time was 14.83 ± 1.61 min, operative time was 58.90 ± 15.76 min and hospital stay were 5.12 ± 0.96 days. Postoperatively, salivary fistulae developed in one patient, Frey's syndrome in two patients, temporary facial paralysis in six patients and temporary numbness in the incision area in six patients. At 6 months postoperatively, 86.5% of patients had a Sunnybrook score of more than 80, and VSS scores and POSAS scores were between one and two.The postoperative complication rate was 30.8%, and the scarring in the facial incision area was mild and close to normal skin at 3 years postoperatively. [ABSTRACT FROM AUTHOR]

This study uses first-principles calculations to investigate the asymmetric Zr2CO/VSe2 heterostructure for hydrogen evolution reaction (HER) applications, focusing on its interlayer interactions, electronic structures, and HER performance across six stacking angles. Our findings demonstrate remarkable structural stability, characterized by interlayer distances of 2.1 Å to 2.7 Å and binding energies from −150.521 to −257.939 meV Å−2. Band structure analyses highlight the heterostructures' exceptional conductivity, essential for catalytic efficiency. Additionally, charge density difference calculations reveal significant charge transfer and redistribution at the interface, providing insights into the interlayer interactions and their influence on catalytic activity. Notably, the Gibbs free energy of hydrogen adsorption (ΔGH*) remains within ±0.1 eV across all configurations, indicating superior HER activity. Further analysis shows that the work function (Φ) serves as a critical electronic structure descriptor, influencing HER performance. The relationship between work function and ΔGH* across different interlayer distances underscores the predictive value of the work function for HER activity. These insights provide a theoretical foundation for developing advanced and effective non-noble metal HER catalysts, paving the way for innovations in sustainable energy technologies. [ABSTRACT FROM AUTHOR]

With the intensification of global climate change, there is an increasing emphasis on protecting natural resources. Mangrove forests, critical to tropical and subtropical intertidal ecosystems, have garnered considerable attention in recent years for their strong carbon sink capacity, rich species diversity, and abundant natural resources. This study utilizes the 2020 global mangrove vector data as a baseline to construct a reasonable buffer zone by calculating the increase in mangrove crown width. The Google Earth Engine (GEE) platform and its Sentinel-2 data from 2022 are employed to acquire synthetic images across all regions using the mosaic algorithm. Then, mangrove forests are extracted using the Otsu algorithm, and a map depicting the global spatial distribution of mangrove forests in 2022 is obtained. The average overall accuracy of the extracted mangrove forests in this study reaches 92.4%, and it is determined that the global mangrove forest area expanded by 4920.6 km2 between 2020 and 2022, This study provides crucial data support for the global monitoring of mangrove changes and holds significant importance for protecting and restoring mangrove ecosystems. [ABSTRACT FROM AUTHOR]

Anti‐inflammatory compounds, delivered as a payload to the gastrointestinal tract (GIT) by carriers, still cannot treat inflammatory bowel diseases without avoiding side effects. Here, we developed payload‐free protein nanoparticles (PNPs) that crossed GIT to retain in the colon and treat colitis by restoring intestinal barrier integrity by modulating gut microbiome and metabolome. Specifically, PNPs, orally administered to mice with acute colitis, reached the colon within three hours. Consequently, PNPs improve gut microbiota dysbiosis to reverse metabolism balance, suppressing the expression of tumor‐necrosis factor α and toll‐like receptor 4 that restores the intestinal barrier integrity. PNPs then ameliorated colon inflammation and attenuated gut microbiota dysbiosis by exerting probiotic effects on gut microbiota, treating colitis in a week more effectively than the clinically often used 5‐aminosalicylic acid without causing undesired side effects. Such PNPs represent safe, sustainable, and cost‐effective therapeutics for treating inflammatory and metabolic diseases by eliminating microbial and metabolomic imbalance. [ABSTRACT FROM AUTHOR]

Boron nitride nanosheets (BNNSs) have garnered significant attention across diverse fields; however, accomplishing on‐demand, large‐scale, and highly efficient preparation of BNNSs remains a challenge. Here, an on‐demand preparation (OdP) method combining high‐pressure homogenization and short‐time ultrasonication is presented; it enables a highly efficient and controllable preparation of BNNSs from bulk hexagonal boron nitride (h‐BN). The homogenization pressure and number of cycles are adjusted, and the production efficiency and yield of BNNSs reach 0.95 g g−1h−1 and 82.8%, respectively, which significantly exceed those attained by using existing methods. The universality of the OdP method is demonstrated on h‐BN raw materials of various bulk sizes from various producers. Furthermore, this method allows the preparation of BNNSs having specific sizes based on the final requirements. Both simulation and experimental results indicate that large BNNSs are particularly suitable for enhancing the thermal conductivity and electrical insulation properties of dielectric polymer nanocomposites. Interestingly, the small BNNS‐filled photonic nanocomposite films fabricated via the OdP method exhibit superior daytime radiative cooling properties. Additionally, the OdP method offers the benefits of low energy consumption and reduced greenhouse gas emissions and fossil energy use. These findings underscore the unique advantages of the OdP method over other techniques for a high‐efficiency and controllable preparation of large BNNSs. [ABSTRACT FROM AUTHOR]