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Searching for inexpensive, efficient and durable electrocatalysts with earth-abundant elements toward the hydrogen evolution reaction (HER) is of vital importance for the future sustainable hydrogen economy, yet still remains a formidable challenge. Herein, a facile template-engaged strategy is demonstrated for the direct in-situ growth of Ni nanoparticles and N-doped carbon nanotubes on carbon nanorod substrates, forming a hierarchically branched architecture (abbreviated as Ni@N-C NT/NRs hereafter). The elaborate construction of such unique hierarchical structure with tightly encapsulated Ni nanoparticles and open configuration endows the as-fabricated Ni@N-C NT/NRs with abundant well-dispersed active sites, enlarged surface area, reduced resistances of charge transfer and mass diffusion, and reinforced mechanical robustness. As a consequence, the optimal Ni@N-C NT/NR catalyst demonstrates superior electrocatalytic activity with relatively low overpotential of 134 mV to deliver a current density of 10 mA·cm −2 and excellent stability for HER in 0.1 M KOH, holding a great promise for practical scalable H 2 production. More importantly, this work offers a reliable methodology for feasible fabrication of robust high-performance carbon-based hierarchical architectures for a variety of electrochemical applications.

Background The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). Methods In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan–Meier analysis. Results Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. Conclusions Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.

Tuberculosis (TB) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics.

Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism. Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science™ (Clarivate™, Philadelphia, PA, USA) database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words. The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research. Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers.

Background: Burns are a global public health issue and a major cause of disability and death around the world. Stem cells, which are the undifferentiated cells with the potential for indefinite proliferation and multilineage differentiation, have the ability to replace injured skin and facilitate the wound repair process through paracrine mechanisms. In light of this, the present study aims to conduct a bibliometric analysis in order to identify research hotspots of stem cell–related burns and assess global research tendencies. Methods: To achieve this objective, we retrieved scientific publications on burns associated with stem cells covering the period from January 1, 1978, to October 13, 2022, from the Web of Science Core Collection (WoSCC). Bibliometric analyses, including production and collaboration analyses between countries, institutions, authors, and journals, as well as keyword and topic analyses, were conducted using the bibliometrix R package, CiteSpace, and VOSviewer. Results: A total of 1648 burns associated with stem cell documents were published and listed on WOSCC. The most contributive country, institution, journal, and author were the United States, LV Prasad Eye Institute, Burns , and Scheffer C.G. Tseng, respectively. More importantly, combined with historical direct citation network, trend topic analysis, keyword co‐occurrence network, and substantial literature analysis, we eventually summarized the research hotspots and frontiers on burns associated stem cell reasearch. Conclusion: The present study obtained deep insight into the developing trends and research hotspots on burns associated with stem cells, which arouses growing concerns and implies increasing clinical implications. The mechanism and therapeutics of epidermal stem cells (ESCs) for burn wounds and the mechanism of mesenchymal stem cells (MSCs) and MSC‐derived exosomes for burns wounds are two research hotspots in this field.

High-throughput structural genomics projects seek to delineate protein structure space by determining the structure of representatives of all major protein families. Generally this is accomplished by processing numerous proteins through standardized protocols, for the most part involving purification of N-terminally His-tagged proteins. Often proteins that fail this approach are abandoned, but in many cases further effort is warranted because of a protein’s intrinsic value. In addition, failure often occurs relatively far into the path to structure determination, and many failed proteins passed the first critical step, expression as a soluble protein. Salvage pathways seek to recoup the investment in this subset of failed proteins through alternative cloning, nested truncations, chemical modification, mutagenesis, screening buffers, ligands and modifying processing steps. To this end we have developed a series of ligation-independent cloning expression vectors that append various cleavable C-terminal tags instead of the conventional N-terminal tags. In an initial set of 16 proteins that failed with an N-terminal appendage, structures were obtained for C-terminally tagged derivatives of five proteins, including an example for which several alternative salvaging steps had failed. The new vectors allow appending C-terminal His 6 -tag and His 6 - and MBP-tags, and are cleavable with TEV or with both TEV and TVMV proteases.

Tuberculosis (TB) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics.

Based on Cassini observations, we report representative electrostatic electron cyclotron harmonic (ECH) wave events observed in Saturn's magnetosphere within remote plasma injections. Unlike local injections, remote injections are “older” injection events that have evolved to form a dispersed signature in particle energy spectrum. We show that Saturnian ECH waves within remote injections present a strong fundamental band and much weaker high harmonic bands. By calculating the linear wave growth rates based on the measured electron velocity distributions, we indicate that Saturnian ECH waves can be excited by the loss cone distribution of remotely injected, hot electrons of ∼100 eV to several keV. We find that ECH waves tend to intensify with increased fluxes of injected hot electrons but weakening with increased evolution time of the flux tubes, which is consistent with the results of wave growth rates and improves the current understanding of the generation of ECH waves at Saturn. Plain Language Summary Saturn possesses a huge magnetosphere formed by the interaction between the solar wind flows and the internal magnetic field. Electrostatic electron cyclotron harmonic (ECH) waves are electrostatic emissions frequently observed in Saturn's magnetosphere, which occur near the half‐integral harmonics of electron cyclotron frequency (fce), that is, (n + 1/2) fce. ECH waves are closely related to the injection events driven by the centrifugal force. Due to the gradient and curvature drift, the injected hot electrons produce dispersion signatures on the energy‐time spectrogram, which is a typical characteristic in the remote injections. In this work, we report typical ECH wave events in the remote injections and investigate the wave generation mechanism. Our results show that the excitation of ECH waves in the remote injections is caused by loss cone instability. The wave growth is dominated by injected hot electrons (∼100 eV–several keV). In addition, we find that ECH wave amplitudes increase as the hot electron fluxes increase and decrease with increasing ages of the injection events. Our results help us to deeply understand the generation of ECH waves in the Saturn's magnetosphere. Key Points The loss cone instability of electrons excites the Saturnian electron cyclotron harmonic (ECH) waves within remote plasma injections The free energy for Saturnian ECH wave growth is mainly provided by remotely injected, hot electrons at energies of ∼100 eV to several keV Saturnian ECH waves intensify with increased fluxes of injected hot electrons but weakening with increased evolution time of the flux tubes

Hospital and community-acquired infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) have emerged as a significant public health challenge, highlighting the urgent need for novel antibiotics. In response, the antibacterial properties of natural products derived from traditional plants are being investigated as potential treatments for multidrug resistance. This study demonstrates the potent antibacterialimoact of Berberine (BBR), a compound derived from traditional Chinese medicine, against the community-associated MRSA (CA-MRSA) strain USA300 LAC. Through a comprehensive series of in vitro antibacterial experiments and gene-level investigations, we discovered that BBR compromises the integrity of the USA300 LAC cell wall structure. This mechanism of action is likely attributed to the inhibition of the tarO gene, which encodes a critical enzyme in the initial stage of wall teichoic acid (WTA) biosynthesis, thereby suppressing WTA synthesis, an essential component of the cell wall. Additionally, BBR upregulates the expression of lytic enzymes LytM and SsaA, resulting in accelerated hydrolysis of peptidoglycan, a major structural element of the cell wall. This disruption ultimately leads to the destruction of the USA300 LAC cell wall. Moreover, combined antibacterial assays reveal that BBR synergistically enhances the antibacterial effect of Oxacillin against USA300 LAC. Overall, our findings elucidate the antibacterial mechanism of BBR, a traditional Chinese medicine monomer, against MRSA and highlight its promising potential for clinical application in the treatment of MRSA.

Background: Older individuals with hypertension are at a high risk of being infected with influenza. However, there have been few studies investigating the influenza vaccination status among older people with hypertension. The present work aimed to estimate the vaccination coverage and determine the predictors of seasonal influenza vaccinations among hypertensive patients aged over 60 years in Shenzhen, China. Method: The study used data from an online cross-sectional survey that was conducted in Shenzhen City, China, in October 2020. Frequencies and proportions of all the variables including sociodemographic characteristics and health-related information were described and tabulated based on the influenza vaccination status. Bivariate and multivariable logistic regression analyses were used to identify independent predictors associated with the influenza vaccination. Results: A total of 5216 older people with hypertension aged above 60 years were recruited. Overall, only 4.7% had received an influenza vaccine in the latest influenza season. Using the action toward being vaccinated as the primary outcome, the multivariable regression analysis showed that participants aged over 80 years (aOR 2.957, 95% CI: 1.784–4.900), obtaining higher education levels (aOR 1.424, 95% CI: 1.060–1.914 for high school, aOR 1.681, 95% CI: 1.066–2.650 for college or above), living with a partner (aOR 1.432, 95% CI: 1.068–1.920), using a family doctor (aOR 2.275, 95% CI: 1.744–2.968), and taking a physical examination 1–2 and ≥3 times each year (aOR 2.107, 95% CI: 1.601–2.772 and aOR 2.118, 95% CI: 1.083–4.143, respectively) were more likely to be vaccinated. In contrast, smokers had less likelihood of having the influenza vaccination than non-smokers (aOR 1.829, 95% CI: 1.208–2.767). Conclusions: The coverage rate of influenza vaccinations is far away from optimistic among older adults with hypertension. Additional works should be undertaken immediately to improve the influenza vaccination status.