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Drug combinations and repurposing have recently provided promising alternatives to cope with the increasingly severe issue of antibiotic resistance and depletion of natural drug molecular repertoires that undermine traditional antibacterial strategies. Closantel, an effective adjuvant, reverses antibiotic resistance in gram-negative bacteria. Herein, the combined antibacterial enantioselectivity of closantel is presented through separate enantiomer studies. Despite yielding unexpected differences, two closantel enantiomers ( R , S ) increased colistin activity against gram-negative bacteria both in vitro and in vivo . The fractional inhibitory concentration indices of R -closantel and S -closantel combined with colistin against Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli ranged from 0.0087 to 0.5004 and from 0.0117 to 0.5312, respectively. This difference was further demonstrated using growth inhibition assays and time-killing curves. Mechanistically, a higher intracellular concentration of R -CLO is more effective in enhancing the antimicrobial activity of combination. A mouse cutaneous infection model confirmed the synergistic stereoselectivity of closantel. This discovery provides novel insights for developing precision medication and containment of increasing antibiotic resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ding, Guo, Fang, Guo, Yang, Li, Li and He.)

Centrifugal blood pumps drive blood flow by regulating blood flow rate, and have been widely used in clinical applications, including extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and extracorporeal circulation carbon dioxide removal (ECCO 2 R). However, because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios, blood pumps face different application conditions in clinical use. In this study, the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Silanes are important in chemistry and material science. The self-redistribution of HSiCl 3 is an industrial process to prepare SiH 4 , which is widely used in electronics and automobile industries. However, selective silane cross-redistribution to prepare advanced silanes is challenging. We now report an enthalpy-driven silane cross-redistribution to access bis-silanes that contain two different types of Si-H bonds in the same molecule. Compared with entropy-driven reactions, the enthalpy-driven reaction shows high regioselectivity, broad substrate scope (62 examples) and high atom economy. Our combined experimental and computational study indicates that the reaction proceeds through a Ni 0 -Ni II -Ni IV catalytic cycle., (© 2022 Wiley-VCH GmbH.)

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, which is often accompanied by oxidative stress. Tempol, a superoxide dismutase mimetic, protects against several diseases caused by oxidative stress. However, the effect of tempol on PCOS has not been investigated. The present study demonstrated the alleviation of ovarian dysfunction and glucose tolerance in dehydroepiandrosterone (DHEA)-induced PCOS rats treated with tempol. Tempol significantly reduced the intestinal oxidative stress in PCOS rats without affecting the ovarian redox rate. The 16S rDNA sequencing of the intestinal microbiome and non-targeted metabolomics analysis indicated significant differences in gut microbiota composition and serum metabolite profiles between the control and PCOS rats, and most of these differences were reduced after tempol intervention. Tempol alters the gut microbiome by increasing the abundance of genus Ruminococcus_1 and by decreasing the abundance of Ruminococcus_2, Staphylococcus, Ideonella, and Corynebnacterium genera. Tempol also attenuates the reduction of serum bile acid and stachyose levels in PCOS rats, and the serum stachyose level was significantly correlated with the abundance of 15 genera, particularly Ruminococcus_1 and Ruminococcus_2. Moreover, stachyose administration improved ovarian dysfunction in PCOS rats. Thus, our data indicate that tempol ameliorates PCOS phenotype by reducing intestinal oxidative stress, restoring gut dysbiosis, and modulating the interaction between gut microbiota and host metabolite. Therefore, tempol intervention is a potential therapeutic approach for PCOS., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To further improve the regulation of medical device Introduction for Use (IFU) and improve the quality of medical device Introduction for Use (IFU)., Methods: Summarize domestic regulatory experience and deficiencies through literature research, and introduce the international experience gathered from the IMDRF coordination document Principles of Labelling for Medical Devices and IVD Medical Devices., Results: The IMDRF international coordination document categorizes ten chapters to define and summarize the basic principles that medical device instructions and labels should contain., Conclusions: According to the current status of medical device specification supervision and drawing on international supervision experience, improvement suggestions are proposed in terms of refining the IFU requires to improve the quality of the instructions, e.g. dynamic adjustment of IFU management requirements, strengthen the management of IFU for home used medical devices, and improving the standardization and rationality of medical device IFU content. We should continue to maintain effective management of medical device IFU.

RNA editing of adenosines to inosines contributes to a wide range of biological processes by regulating gene expression post-transcriptionally. To understand the effect, accurate mapping of inosines is necessary. The most conventional method to identify an editing site is to compare the cDNA sequence with its corresponding genomic sequence. However, this method has a high false discovery rate because guanosine signals, due to experimental errors or noise in the obtained sequences, contaminate genuine inosine signals detected as guanosine. To ensure high accuracy, we developed the Inosine Chemical Erasing (ICE) method to accurately and biochemically identify inosines in RNA strands utilizing inosine cyanoethylation and reverse transcription-PCR. Furthermore, we applied this technique to next-generation sequencing technology, called ICE-seq, to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome.

As the main constituent of the largest cellular ribonucleoprotein complex, the evolutionary highly conserved major vault protein (MVP) has been proposed play vital roles in the regeneration of multiple organs. In current study, we use a mvp knockout zebrafish line recently generated to characterize the function of MVP during organ regeneration. We found the regenerative capacity of heart, spinal cord and fin is preserved in mvp knockout zebrafish. Further experiments demonstrated in injured mvp knockout zebrafish, the cell death is enhanced while the transcriptome landscape is largely unchanged. These data showed MVP acts as an anti-apoptotic factor at early phase of injury response while plays a dispensable role in the regenerative programs in zebrafish., (© 2020 The Author(s).)

Pancreatic cancer (PCa) is one of the most fatal cancers worldwide. Recently, many studies have confirmed that long non-coding RNAs (lncRNAs) play crucial roles in the development of many human cancers, including PCa. The purpose of the present study was to investigate the biological role and underlying mechanisms of lncRNA small nucleolar RNA host gene 1 (SNHG1) in PCa progression. The results demonstrated that the expression levels of SNHG1 were increased in PCa cell lines and human tissue samples. High SNHG1 expression was notably correlated with adverse characteristics and poor survival of PCa patients. Knockdown of SNHG1 suppressed PCa cell proliferation in vitro and PCa tumor growth in vivo, and these effects might be associated with the induction of cell cycle arrest. We further confirmed that, in PCa cells, SNHG1 can negatively regulate miR-195 expression by acting as a ceRNA, and Cyclin D1 is a direct target of miR-195. Overexpression of miR-195 abrogated the oncogenic role of SNHG1 in PCa cells. Collectively, our results identified SNHG1 as a novel oncogenic lncRNA in PCa, and indicated that SNHG1/miR-195/Cyclin D1 axis might be a potential therapeutic target for PCa patients., Competing Interests: None., (IJCEP Copyright © 2019.)

Perovskite ceramics and single crystals are commonly hard and brittle due to their small maximum elastic strain. Here, large-scale BaTi 0.95 Co 0.05 O 3 (BTCO) film with a SrRuO 3 (SRO) buffered layer on a 10 µm thick mica substrate is flexible with a small bending radius of 1.4 mm and semitransparent for visible light at wavelengths of 500-800 nm. Mica/SRO/BTCO/Au cells show bipolar resistive switching and the high/low resistance ratio is up to 50. The resistive-switching properties show no obvious changes after the 2.2 mm radius memory being written/erased for 360 000 cycles nor after the memory being bent to 3 mm radius for 10 000 times. Most importantly, the memory works properly at 25-180 °C or after being annealed at 500 °C. The flexible and transparent oxide resistive memory has good prospects for application in smart wearable devices and flexible display screens., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)