In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delic...
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In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with < 10 nM potency. In addition, the bicyclic compounds 9B exhibited improved FASSIF solubility over the tetracyclic compound MK-8876. This strategic approach demonstrated that, even within limited reaction scope, multi-step parallel libraries could provide access to more complex chemical space. This expedient access facilitates diverse, purpose-driven optimization of SAR and physicochemical properties.
Fluoroquinolones (FQs) present in water environments pose threats to aquatic organisms. The concentration of FQs adsorbed onto sediments is generally higher than that in water. here, we studied the toxicities of two F...
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Fluoroquinolones (FQs) present in water environments pose threats to aquatic organisms. The concentration of FQs adsorbed onto sediments is generally higher than that in water. here, we studied the toxicities of two FQ antibiotics, norfloxacin (NOR) and ofloxacin (OFL), on the snail Bellamya aeruginosa, an adaptable benthic animal. For this, we performed acute toxicity experiments on young snails and sub-chronic exposure experiments on adult snails by exposure to the FQs for 1-28 days. The 96 h median effective concentrations showed that NOR toxicity was higher than OFL toxicity, although both NOR and OFL were low-toxicity substances (EC50 > 100 mg L-1). Four concentrations were used in the sub-chronic exposure experiments. Results of the measurement of bioconcentration factors (BCF) showed that OFL accumulation was higher than NOR accumulation in snail tissues. During the depuration period (28-49 days), at low concentrations (2 and 20 mu g L-1), both FQs required at least 7 days to reach the maximum residue limit (50 mu g kg(-1)). Conversely, at high concentrations (200 and 2000 mu g L-1), 14 days (NOR) and 21 days (OFL) were required. Our results could facilitate management of the environmental risks of antibiotics and conservation of aquatic animals.
Chinese cities have made significant progress in fostering low-carbon societies and piloting a variety of low-carbon measures. Nonetheless, the effective implementation of these initiatives and the long-term upkeep of...
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Chinese cities have made significant progress in fostering low-carbon societies and piloting a variety of low-carbon measures. Nonetheless, the effective implementation of these initiatives and the long-term upkeep of related amenities rely heavily on resident support. The existing studies provide limited insight into how local residents perceive and endorse different types of low-carbon measures, which often involve varying trade-offs. Addressing this gap, the present study surveyed the willingness to pay (WTP) of residents in Hangzhou-an early adopter of low-carbon practices in China-across five representative low-carbon measures. Survey data were collected from 13 distinct residential neighborhoods. The results indicate that Hangzhou residents are more inclined to financially support measures offering direct personal benefits compared to those benefiting the collective good, with this tendency being notably pronounced among highly educated individuals. Further findings include the following: (1) respondents aware of ongoing low-carbon measures were more willing to pay for them;(2) male respondents, recent migrants (within the past five years), high-income groups, and residents in aging communities tended to contribute higher amounts;(3) providing detailed information on carbon mitigation effects markedly increased both the likelihood and the magnitude of WTP;(4) the promotion of new energy vehicles (NEVs) remains contentious, particularly between NEV owners and gasoline vehicle owners. These findings highlight the need for targeted policies and educational programs to strengthen public awareness and support for low-carbon interventions, thereby advancing sustainability in fast-growing urban centers like Hangzhou. Overall, these findings provide key insights for the formulation of low-carbon city policies and sustainable urban planning, emphasizing the global importance of local socioeconomic dynamics and offering a valuable reference for cities worldwide seeking
This disclosure is directed, at least in part, to AMPK activators useful for the treatment of conditions or disorders associated with AMPK. In some embodiments, the condition or disorder is associated with the gut-bra...
标准号:
WO2021/263039(A1)
This disclosure is directed, at least in part, to AMPK activators useful for the treatment of conditions or disorders associated with AMPK. In some embodiments, the condition or disorder is associated with the gut-brain axis. In some embodiments, condition or disorder is associated with systemic infection and inflammation from having a leaky gut barrier. In some embodiments, the AMPK activators are gut-restricted compounds. In some embodiments, the AMPK activators are agonists, super agonists, full agonists, or partial agonists.
沙门氏菌是全球范围内危害公众健康的主要食源性致病菌,每年造成千万人食物中毒。黏附于食品加工接触面的生物菌膜是沙门氏菌交叉污染的源头,其对消毒剂具有极强的耐受抵抗作用,可引发大规模食物中毒并导致食品召回。本文在论述细菌黏附辅助体(菌毛和鞭毛)和胞外多聚物对生物菌膜的具体作用及其在mRNA转录层面调控效应的基础上,重点阐述了转录后层面上的非编码小RNA(non-coding small RNA,sRNA)及其对移动性、胞外多聚物等核心mRNA通路的调控机制,并归纳出sRNA调控生物菌膜的4种作用模式,最后对该领域的研究前景进行了前瞻性展望,以期为拓展研究思路、完善生物菌膜的科学理论和研发针对性控制技术提供参考。
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