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Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here, we find that a broad range of ribosome-targeting antibiotics cause mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we find that the translation inhibitor causes genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis shows that the stalling is caused by the disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induce lesions to the DNA via transcription-coupled repair. While most of the bacteria are killed by genotoxicity, a small subpopulation acquires mutations via SOS-induced mutagenesis. Given that these processes are triggered shortly after antibiotic addition, resistance rapidly emerges in the population. Our work reveals a mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance. Bacteria evolve antibiotic resistance via genetic mutations, but the process remains somewhat unclear. This work finds that the disruption of transcription-translation coupling is crucial for mutagenesis caused by ribosome-targeting antibiotics in Escherichia coli .

Core-shell-structured system has been proved as one of the best architecture for clean energy products owing to its inherited superiorities from both the core and the shell part, which can provide better conductivity and high surface area. Herein, a hierarchical core-shell NiCo 2 S 4 @NiMoO 4 heterostructure nanotube array on Ni foam (NF) (NiCo 2 S 4 @NiMoO 4 /NF) has been successfully fabricated. Because of its novel heterostructure, the capacitive performance has been enhanced. A specific capacitance up to 2006 F g -1 was obtained at a current density of 5 mA cm -2 , which was far higher than that of pristine NiCo 2 S 4 nanotube arrays (about 1264 F g -1 ). More importantly, NiCo 2 S 4 @NiMoO 4 /NF and active carbon (AC) were congregated as positive electrode and negative electrode in an asymmetric supercapacitor. As-fabricated NiCo 2 S 4 @NiMoO 4 /NF//AC device has a good cyclic behavior with 78% capacitance retention over 2000 cycles, and exhibits a high energy density of 21.4 Wh kg -1 and power density of 58 W kg -1 at 2 mA cm -2 . As displayed, the NiCo 2 S 4 @NiMoO 4 /NF core-shell herterostructure holds great promise for supercapacitors in energy storage.

In this paper, a novel electromagnetic blank holding system (EBHS) for a conventional drawing process is proposed. The system is created to substitute mechanical or hydraulic blank holder force (BHF) with mutually attractive electromagnetic force (EMF). The winding type of electromagnetic coils is determined as a single-coil through numerical simulation. For avoiding the fluctuation of the magnitude of BHF, direct current is chosen to generate BHF. Corresponding magnetic circuit model of the electromagnetic blank holding device (EBHD) has been established to find the mathematical relationship between EMF and input voltage. Besides, several groups of EMF testing data are measured to prove the correction of deduced expression. To validate the feasibility of the novel system, corresponding numerical simulation and experiment have been carried out. It is worth to mention that the cylindrical parts created by simulation and experiment at different BHF agree well with each other. Additionally, the thickness reduction rate of drawn part is controlled at a reasonable level with the application of EBHS, which well validates the effectiveness of the EBHS.

The genus Orbivirus includes a number of important pathogenic viruses, including Bluetongue virus (BTV), African horse sickness virus (AHSV), and Epizootic hemorrhagic disease virus (EHDV). In this study we describe the isolation and characterization of an Orbivirus strain isolated from Anopheles maculatus mosquitoes collected in Tibet, China. Initial viral screening identified a viral strain (XZ0906) that caused significant cytopathic effect (CPE) in BHK-21 cells, including rounding, cell rupture, and floating. Although CPE was not observed in insect cells (C6/36), these cells supported viral replication. Polyacrylamide gel analysis revealed a genome consisting of 10 segments of double-stranded RNA (dsRNA), with a distribution pattern of 3-3-3-1. 454 high throughput sequencing of culture supernatant was used for viral identification. Complete genome sequencing was performed by Sanger sequencing in combination with 5'-RACE and 3'-RACE. Sequence analysis demonstrated that all 5'- and 3'- untranslated regions (UTRs) for each of the 10 genome segments contained a series of six highly conserved nucleotides. In addition, homology analysis and phylogenetic analysis based on amino acid sequence was completed, and all results show that virus XZ0906 was not a member of any known species or serotype of Orbivirus, indicating it to be a new species within the genus Orbivirus. The isolated Orbivirus strain was designated Tibet Orbivirus, TIBOV to denote the location from which it was isolated. TIBOV is a novel orbivirus species which is isolated from Anopheles maculatus mosquitoes collected in Tibet, China.

The function of natural killer (NK) cells, defending against virus infection and tumour progression, is regulated by multiple activating and inhibiting receptors expressed on NK cells, among which sialic acid-bind immunoglobulin-like lectins (Siglecs) act as a vital inhibitory group. Previous studies have shown that Siglec7 and Siglec9 are expressed on NK cells, which negatively regulate the function of NK cells and modulate the immune response through the interaction of sialic acid-containing ligands. Siglec7 and Siglec9 are very similar in distribution, gene encoding, protein sequences, ligand affinity, and functions in regulating the immune system against virus and cancers, but differences still exist between them. In this review, we aim to discuss the similarities and differences between Siglec7 and Siglec9 and analyze their functions in virus infection and tumour progression in order to develop better anti-viral and anti-tumor immunotherapy in the future.

Waste tyres (WTs) are a major global issue that needs immediate attention to ensure a sustainable environment. They are often dumped in landfills or incinerated in open environments, which leads to environmental pollution. However, various thermochemical conversion methods have shown promising results as treatment routes to tackle the WT problem while creating new materials for industries. One such material is WT char, which has properties comparable to those of carbon materials used as an active electrode material in batteries. Therefore, a systematic review of the various thermochemical approaches used to convert WTs into carbon materials for electrode applications was conducted. The review shows that pretreatment processes, various process routes, and operating parameters affect derived carbon properties and its respective electrochemical performance. WT‐derived carbon has the potential to yield a high specific capacity greater than the traditional graphite (372 mAh g−1) commonly used in lithium‐ion batteries. Finally, the review outlines the challenges of the process routes, as well as opportunities and future research directions for electrode carbon materials from WTs. Thermochemical conversion routes such as pyrolysis, carbonization, and activation and molten salt carbonization activation are currently applied to transform waste tyres (WTs) into valuable carbon black. These conversion approaches not only reduce the burden of disposal but also provide valuable resources for various industries, contributing to circular economy principles and mitigating environmental concerns associated with WTs.

Background Extravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood. Methods The effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease. Results This study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss. Conclusions This work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications. E9R9tt1jd9fu3QritsNs7Q Video Abstract

A simple carbon black (Ketjenblack, KB)‐multiwall carbon nanotubes (MWCNTs) composite was fabricated and used as the air cathode in a Li‐O2 battery where MWCNTs primarily serve as microscopic cables to enhance long‐range electronic conductivity. With optimal KB:MWCNTs mass ratios, the composite exhibited significantly improved specific capacity (up to 10611 mAh/gcarbon under 100 mAh/gcarbon), rate capability (up to 9598 mAh/gcarbon under 500 mAh/gcarbon) and cyclability than pristine KB, owing to the synergy of KB's abundant surface area for accommodation of discharge products and MWCNTs’ long‐range electronic conductivity to guide even and compact deposition of discharge products, and mitigate passivation/clogging of the air cathode surface during discharge. This strategy of using MWCNTs as microscopic cables could also be applied for other commercial materials to construct high‐performance and low‐cost air cathodes. A simple carbon black (Ketjenblack, KB)‐multiwall carbon nanotubes (MWCNTs) composite was fabricated and used as the air cathode in a Li‐O2 battery, achieving significantly improved specific capacity (up to 10611 mAh/gcarbon), rate capability and cyclability than pristine KB, owing to the synergy of KB's abundant surface area for accommodation of discharge products and MWCNTs’ long‐range electronic conductivity.

Background There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism. Methods The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells. Results CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC. Conclusion CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.