Easy processing and flexibility of polymer electrolytes make them very promising in developing all-solid-state lithium batteries. However, their low room-temperature conductivity and poor mechanical and thermal properties still hinder their applications. Here, we use LiLaZrTaO (LLZTO) ceramics to trigger structural modification of poly(vinylidene fluoride) (PVDF) polymer electrolyte. By combining experiments and first-principle calculations, we find that La atom of LLZTO could complex with the N atom and C═O group of solvent molecules such as N,N-dimethylformamide along with electrons enriching at the N atom, which behaves like a Lewis base and induces the chemical dehydrofluorination of the PVDF skeleton. Partially modified PVDF chains activate the interactions between the PVDF matrix, lithium salt, and LLZTO fillers, hence leading to significantly improved performance of the flexible electrolyte membrane (e.g., a high ionic conductivity of about 5 × 10 S cm at 25 °C, high mechanical strength, and good thermal stability). For further illustration, a solid-state lithium battery of LiCoO|PVDF-based membrane|Li is fabricated and delivers satisfactory rate capability and cycling stability at room temperature. Our study indicates that the LLZTO modifying PVDF membrane is a promising electrolyte used for all-solid-state lithium batteries.
Reciprocal interactions between the metabolic system and immune cells play pivotal roles in diverse inflammatory diseases, but the underlying mechanisms remain elusive. The activation of bile acid-mediated signaling has been linked to improvement in metabolic syndromes and enhanced control of inflammation. Here, we demonstrated that bile acids inhibited NLRP3 inflammasome activation via the TGR5-cAMP-PKA axis. TGR5 bile acid receptor-induced PKA kinase activation led to the ubiquitination of NLRP3, which was associated with the PKA-induced phosphorylation of NLRP3 on a single residue, Ser 291. Furthermore, this PKA-induced phosphorylation of NLRP3 served as a critical brake on NLRP3 inflammasome activation. In addition, in vivo results indicated that bile acids and TGR5 activation blocked NLRP3 inflammasome-dependent inflammation, including lipopolysaccharide-induced systemic inflammation, alum-induced peritoneal inflammation, and type-2 diabetes-related inflammation. Altogether, our study unveils the PKA-induced phosphorylation and ubiquitination of NLRP3 and suggests TGR5 as a potential target for the treatment of NLRP3 inflammasome-related diseases.
a b s t r a c tObjective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.
Objective: Evidence-based practice (EBP) provides nurses with a method to use critically appraised and scientifically proven evidence for delivering quality health care to a specific population. The objective of this study was to explore nurses' awareness of, knowledge of, and attitude toward EBP and factors likely to encourage or create barriers to adoption. In addition, information sources used by nurses and their literature searching skills were also investigated.Method: A total of 2,100 copies of the questionnaire were distributed to registered nurses in 2 public hospitals in Singapore, and 1,486 completed forms were returned, resulting in a response rate of 70.8%.Results: More than 64% of the nurses expressed a positive attitude toward EBP. However, they pointed out that due to heavy workload, they cannot keep up to date with new evidence. Regarding self-efficacy of EBP-related abilities, the nurses perceived themselves to possess moderate levels of skills. The nurses also felt that EBP training, time availability, and mentoring by nurses with EBP experience would encourage them to implement EBP. The top three barriers to adopting EBP were lack of time, inability to understand statistical terms, and inadequate understanding of the jargon used in research articles. For literature searching, nurses were using basic search features and less than one-quarter of them were familiar with Boolean and proximity operators. Conclusion:Although nurses showed a positive attitude toward EBP, certain barriers were hindering their smooth adoption. It is, therefore, desirable that hospital management in Southeast Asia, particularly in Singapore, develop a comprehensive strategy for building EBP competencies through proper training. Moreover, hospital libraries should also play an active role in developing adequate information literacy skills among the nurses.
Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in families. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the γ-secretase multiprotein complex. Our results identify the γ-secretase component genes as the culprits for a subset of familial AI, implicate the γ-secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.
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