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Importantly, the combination therapy of Meropenem and metal complexes significantly suppressed the development of higher-level resistance in bacteria producing NDM-1, also effectively reduced the bacterial burden in liver and spleen of mice infected by carbapenem-resistant Enterobacteriaceae producing NDM-1. These findings will offer potential lead compounds for the further development of clinically useful inhibitors targeting MβLs.CRISPR-Cas12a, a type-V CRISPR-Cas endonuclease, is an effective genome editing platform. To improve the gene editing efficiency of Cas12a, we rationally designed small molecule enhancers through a combined computational approach. First, we used extensive molecular dynamics (MD) simulations to explore the conformational landscape of Cas12a from Acidaminococcus (AsCas12a), revealing distinct conformational states that could be targeted by small molecules to modulate its genome editing function. We then identified 57 compounds that showed different binding behavior and stabilizing effects on these distinct conformational states using molecular docking. After experimental testing 6 of these 57 compounds, compound 1, quinazoline-2,4(1H,3H)-dione, was found particularly promising in enhancing the AsCas12a-mediated genome editing efficiency in human cells. Compound 1 was shown to act like a molecular "glue" at the interface between AsCas12a and crRNA near the 5'-handle region, thus specifically stabilizing the enzyme-crRNA complex. These results provide a new paradigm for future design of small molecules to modulate the genome editing of the CRISPR-Cas systems.All-inorganic lead halide perovskite solar cells (PSCs) have drawn widespread interest because of its excellent thermal stability compared to its organic-inorganic hybrid counterpart. Poor phase stability caused by moisture, however, has thus far limited their commercial application. https://www.selleckchem.com/products/ag-221-enasidenib.html Herein, by modifying the interface between the hole-transport layer (HTL) and the perovskite light absorption layer, and by optimizing the HTL for better energy alignment, we controlled the growth of perovskite, reduced carrier recombination, facilitated carrier injection and transport, and improved the PSC's power conversion efficiency (PCE) and moisture stability. When testing using a positive bias scan, we obtained a significant improvement in PCE, 9.49%, which is the champion efficiency of CsPbIBr2-based inverted PSC at present. The stability measurement shows that the passivated CsPbIBr2-based inverted PSCs can retain 86% of its initial efficiency after 1000 h preserved in ambient air with 65% relative humidity. This study paves a new way for enhancing the moisture stability and power conversion efficiency of CsPbIBr2-based PSCs.The ubiquity of microplastics in aquatic and terrestrial environments and related ecological impacts have gained global attention. Microplastics have been detected in table salt, drinking water, and air, posing inevitable human exposure risk. However, rigorous analytical methods for detection and characterization of microplastics remain scarce. Knowledge about the potential adverse effects on human health via dietary and respiratory exposures is also limited. To address these issues, we reviewed 46 publications concerning abundances, potential sources, and analytical methods of microplastics in table salt, drinking water, and air. We also summarized probable translocation and accumulation pathways of microplastics within human body. Human body burdens of microplastics through table salt, drinking water, and inhalation were estimated to be (0-7.3)×104, (0-4.7)×103, and (0-3.0)×107 items per person per year, respectively. The intake of microplastics via inhalation, especially via indoor air, was much higher than those via other exposure routes. Moreover, microplastics in the air impose threats to both respiratory and digestive systems through breathing and ingestion. Given the lifetime inevitable exposure to microplastics, we urgently call for a better understanding of the potential hazards of microplastics to human health.Bacteriophage endolysin is one of the potential alternatives of conventional antibiotics, but the intrinsic limitations of the bacterial expression system may undermine the comprehensive application of this therapeutic protein. To circumvent such limitations, we adopted a yeast surface display system as a novel expression platform for endolysin. Endolysin LysSA11 from staphylococcal phage SA11 was expressed and surface-displayed in Saccharomyces cerevisiae to exhibit sufficient antimicrobial activity against Staphylococcus aureus. Without any protein isolation or purification procedures, we showed that direct treatment of LysSA11-displaying yeast cells could accomplish a 5-log reduction of viable Staphylococcus aureus within 3 h. Furthermore, the surface-displayed LysSA11 exhibited superior stability over the soluble form of purified LysSA11 during 14 days of storage in a refrigerated environment. We suggest that the yeast surface display system is an efficient, stable, and straightforward platform for the production and antibacterial applications of endolysin.Quantifying greenhouse gas (GHG) emissions and setting GHG emissions budgets for anthropogenic systems are influenced by several value and modeling choices. This study, for the first time, quantified the influence of choice of GHG accounting approach, GHG metric, time horizon, climate threshold, global emissions budget calculation method, and effort-sharing approach, taking New Zealand (NZ) as a case study. First, NZ's production- and consumption-based emissions were quantified using multiregional input-output analysis and applying different GHG metrics (global warming and temperature potentials) and time horizons (20 and 100 years). Second, global emissions budgets for 1.5 °C, 2 °C, and 1 W m-2 climate thresholds were estimated. Budget shares were then assigned to NZ using two effort-sharing approaches (grandfathering and economic value), and emissions were benchmarked against the assigned shares. Finally, the analysis was undertaken at the NZ sector level. The results showed that, for each GHG accounting approach, NZ's total emissions exceeded their budget shares, irrespective of the choices; the largest source of uncertainty was the choice of global emissions budget calculation method, followed by GHG metric, climate threshold, effort-sharing approach, and reference year for the grandfathering approach.

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