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Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS). Preliminary analysis utilised SLE GWAS data from FinnGen. The primary method for causal analysis relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Steiger testing and linkage disequilibrium score regression were employed to validate the identified metabolites. This study identified 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) [odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015–0.773, P = 0.027), gamma-glutamylthreonine (OR = 0.077, 95% CI: 0.010–0.574, P = 0.012), 5-dodecenoate(12:1n7) (OR = 0.205, 95% CI: 0.061–0.685, P = 0.010), linoleoylglycerophosphoethanolamine * (OR = 0.159, 95% CI: 0.027–0.933, P = 0.044), erythrose (OR = 88.331,95% CI:1.098–63.214, P = 0.040) and 1-, adrenate (22:4n6) (OR = 9.876, 95% CI: 1.753–55.639, P = 0.001)]. Additionally, we found associations between SLE and six unknown chemical structures: X-06351 (OR = 0.071, 95% CI: 0.006–0.817, P = 0.034), X-10810 (OR = 4.268 95% CI: 1.260–14.459, P = 0.020), X-11412 (OR = 5.418 95% CI: 1.068–27.487, P = 0.041), X-11905 (OR = 0.551, 95%CI: 0.304–0.997, P = 0.049), X-12038 (OR = 0.178 95%CI: 0.032–0.988, P = 0.045), X-12217 (OR = 0.174 95%CI: 0.044–0.680, P = 0.014). This study offers evidence supporting a causal relationship between SLE and 12 circulating metabolites, six of which have known chemical structures and six that remain unidentified. These findings introduce a new perspective for further exploration of SLE mechanisms.

Bacteriophages are abundant in soils. However, the majority are uncharacterized, and their hosts are unknown. Here, we apply high-throughput chromosome conformation capture (Hi–C) to directly capture phage-host relationships. Some hosts have high centralities in bacterial community co-occurrence networks, suggesting phage infections have an important impact on the soil bacterial community interactions. We observe increased average viral copies per host (VPH) and decreased viral transcriptional activity following a two-week soil-drying incubation, indicating an increase in lysogenic infections. Soil drying also alters the observed phage host range. A significant negative correlation between VPH and host abundance prior to drying indicates more lytic infections result in more host death and inversely influence host abundance. This study provides empirical evidence of phage-mediated bacterial population dynamics in soil by directly capturing specific phage-host interactions. This study uses high-throughput chromosome conformation capture (Hi-C) to identify phage–host relationships in soil. By coupling Hi-C with DNA and RNA sequencing, the authors demonstrate the impact of soil drying on phage–host interactions and the downstream effects on abundances and interspecies interactions within bacterial communities.

Background: The overuse of antibiotics is a serious public health problem and a major challenge in China, and China lacks up-to-date evidence on the nationwide antibiotic use in different healthcare settings. The changes of China’s antibiotic use under the COVID-19 pandemic are still unknown. Objective: This study aimed to investigate the use of antibiotics in China’s public medical institutions based on a three-year nationwide surveillance and to examine the impact of the COVID-19 pandemic on China’s antibiotic consumption. Methods: This study used nationwide drug procurement data from the China Drug Supply Information Platform (CDSIP). We retrospectively analyzed antibiotic procurement data of 9,176 hospitals and 39,029 primary healthcare centers (PHCs) from 31 provinces in mainland China from January 2018 to December 2020. Antibiotic utilization was measured by defined daily doses (DDDs) and DDD per 1,000 inhabitants per day (DID). Generalized linear regression models were established to quantify the impact of the COVID-19 pandemic on antibiotic use. Results: The total antibiotic consumption among all healthcare settings increased from 12.94 DID in 2018 to 14.45 DID in 2019, and then dropped to 10.51 DID in 2020. More than half of antibiotics were consumed in PHCs, especially in central regions (59%–68%). The use of penicillins (J01C) and cephalosporins (J01D) accounted for 32.02% and 28.86% of total antibiotic consumption in 2020. During 2018–2020, parenteral antibiotics accounted for 31%–36% of total antibiotic consumption; the proportion is more prominent in central and western regions and the setting of hospitals. Access category antibiotics comprised 40%–42% of the total utilization. Affected by COVID-19, the antibiotic consumption was significantly dropped both in hospitals ( β = −.11, p < .001) and PHCs ( β = −.17, p < .001), as well as in total ( β = −.14, p < .001). Significant increments were observed in the proportion of total antibiotics ( β = .02, p = .024) consumed in hospitals (against the consumption in all healthcare settings), as well as parenteral antibiotics ( β = 1.73, p = .001). Conclusion: The consistent preferred use of penicillin and cephalosporin, as well as injections, among China’s public healthcare institutions should draw concern. China’s antibiotic consumption significantly declined during the COVID-19 pandemic, which brings opportunities for antibiotic use management in China.

Background Systemic lupus erythematosus (SLE) is a debilitating autoimmune condition characterized by limited therapeutic options. Dihydroartemisinin (DHA), an antimalarial compound, exhibits promising immunomodulatory effects against SLE; however, its clinical application is limited by poor bioavailability. Methods This study presented an innovative DHA delivery system based on macrophage membrane-coated nanoparticles (CCR2-MM@PEG-PCL/DHA), engineered to target SLE and its severe renal manifestation, lupus nephritis (LN). CCL2, a central mediator of leukocyte chemotaxis, contributes significantly to SLE pathogenesis. The targeting ability of nanoparticles to inflammatory sites is enhanced by genetically modifying the membrane of macrophages to over-express CCR2, and the nanoparticles can act as \"nanobait\" to capture CCL2 in the inflammatory microenvironment, thereby inhibiting macrophage-mediated inflammation. Efficacy was evaluated in vitro and in vivo using the MRL/lpr murine model. Results The findings showed that this nanosystem effectively alleviated symptoms in the MRL/lpr mouse model of SLE. Furthermore, CCR2-MM@PEG-PCL/DHA modulated the renal immune microenvironment by reducing monocyte/macrophage infiltration and reprogramming the M1/M2 macrophage balance, thus mitigating kidney damage in SLE mice. Conclusions The study establishes a mechanistically informed strategy for SLE intervention, substantiated by robust in vitro and in vivo data. These findings lay the foundation for translational research and potential clinical advancement in SLE therapy.

Metagenomics is unearthing the previously hidden world of soil viruses. Many soil viral sequences in metagenomes contain putative auxiliary metabolic genes (AMGs) that are not associated with viral replication. Here, we establish that AMGs on soil viruses actually produce functional, active proteins. We focus on AMGs that potentially encode chitosanase enzymes that metabolize chitin – a common carbon polymer. We express and functionally screen several chitosanase genes identified from environmental metagenomes. One expressed protein showing endo-chitosanase activity (V-Csn) is crystalized and structurally characterized at ultra-high resolution, thus representing the structure of a soil viral AMG product. This structure provides details about the active site, and together with structure models determined using AlphaFold, facilitates understanding of substrate specificity and enzyme mechanism. Our findings support the hypothesis that soil viruses contribute auxiliary functions to their hosts. Metagenomics is revealing auxiliary metabolic genes (AMGs) in soil viral genomes. Here, authors solve the crystal structure for a soil viral AMG product, free and ligand bound, and show the protein can decompose chitin, a common carbon polymer.

As a specific force sensor, the tri-axis accelerometer is one of the core instruments in an inertial navigation system (INS). During navigation, its measurement error directly induces constant or alternating navigation errors of the same order of magnitude. Moreover, it also affects the estimation accuracy of gyro drift coefficients during the initial alignment and calibration, which will indirectly result in navigation errors accumulating over time. Calibration can effectively improve measurement accuracy of the accelerometer. Device-level calibration can identify all of the parameters in the error model, and the system-level calibration can accurately estimate part of these parameters. Combining the advantages of both the methods and making full use of the precise angulation of the space-stabilized platform, this paper proposes a three-stage accelerometer self-calibration technique that can be implemented directly in the space-stable INS. The device-level calibration is divided into two steps considering the large amount of parameters. The first step is coarse calibration, which identifies parameters except for the nonlinear terms, and the second step is fine calibration, which not only identifies the nonlinear parameters, but also improves the accuracy of the parameters identified in the first step. The follow-on system-level calibration is carried out on part of the parameters using specific force error and attitude error to further improve the calibration accuracy. Simulation result shows that by using the proposed three-stage calibration technique in the space-stable INS, the estimation accuracy of accelerometer error can reach 1 × 10 − 6   g order of magnitude. Experiment results show that after the three-stage calibration, the accuracy of latitude, longitude, and attitude angles has increased by over 45% and the accuracy of velocity has increased by over 22% during navigation.

Biological nitrogen fixation (BNF) is an important natural biochemical process converting the inert dinitrogen gas (N 2 ) in the atmosphere to ammonia (NH 3 ) in the N cycle. In this study, the nifH gene was chosen to detect the diazotrophic microorganisms with high-throughput sequencing from five acidic forest soils, including three natural forests and two re-vegetated forests. Soil samples were taken in two seasons (summer and winter) at two depth layers (surface and lower depths). A dataset of 179,600 reads obtained from 20 samples were analyzed to provide the microbial community structure, diversity, abundance, and relationship with physiochemical parameters. Both archaea and bacteria were detected in these samples and diazotrophic bacteria were the dominant members contributing to the biological dinitrogen fixation in the acidic forest soils. Cyanobacteria , Firmicutes , Proteobacteria , Spirocheates , and Verrucomicrobia were observed, especially the Proteobacteria as the most abundant phylum. The core genera were Bradyrhizobium and Methylobacterium from α-Proteobacteia , and Desulfovibrio from δ-Proteobacteia in the phylum of Proteobacteia of these samples. The diversity indices and the gene abundances of all samples were higher in the surface layer than the lower layer. Diversity was apparently higher in re-vegetated forests than the natural forests. Significant positive correlation to the organic matter and nitrogen-related parameters was observed, but there was no significant seasonal variation on the community structure and diversity in these samples between the summer and winter. The application of high-throughput sequencing method provides a better understanding and more comprehensive information of diazotrophs in acidic forest soils than conventional and PCR-based ones.

Soil is known to harbor viruses, but the majority are uncharacterized and their responses to environmental changes are unknown. Here, we used a multi-omics approach (metagenomics, metatranscriptomics and metaproteomics) to detect active DNA viruses and RNA viruses in a native prairie soil and to determine their responses to extremes in soil moisture. The majority of transcribed DNA viruses were bacteriophage, but some were assigned to eukaryotic hosts, mainly insects. We also demonstrated that higher soil moisture increased transcription of a subset of DNA viruses. Metaproteome data validated that the specific viral transcripts were translated into proteins, including chaperonins known to be essential for virion replication and assembly. The soil viral chaperonins were phylogenetically distinct from previously described marine viral chaperonins. The soil also had a high abundance of RNA viruses, with highest representation of Reoviridae. Leviviridae were the most diverse RNA viruses in the samples, with higher amounts in wet soil. This study demonstrates that extreme shifts in soil moisture have dramatic impacts on the composition, activity and potential functions of both DNA and RNA soil viruses.Wu et al. use a multi-omics approach (metagenomics, metatranscriptomics, and metaproteomics) to characterize soil viral responses to soil moisture. The results indicate that extreme shifts in soil moisture have dramatic impacts on the composition, activity and potential functions of both DNA and RNA soil viruses.

Plasmids play significant roles in microbial adaptation to ecosystems, yet their dynamics remain poorly understood due to identification challenges. We present the Global Soil Plasmidome Resource (GSPR), a comprehensive dataset of 98,728 plasmid sequences amassed from 6860 terrestrial microbial communities and isolates. We explore this resource through various computational approaches, including phylogenetic diversity analysis, host prediction, and extensive functional annotation, to understand the contribution of plasmids to the genetic and functional diversity in soil, correlating these findings with sample type, as well as the soil habitat they were retrieved from. Our analysis reveals insights into plasmid-encoded functions such as effector modules, quorum sensing, and stress resistance, which may contribute to their persistence and microbial adaptation in soil. Furthermore, CRISPR analysis suggests a prevalent role of these elements related to intra-plasmid competition. By contrasting plasmids from cultivated and uncultivated organisms, we identify important functions that expand existing knowledge of plasmid roles in these habitats. This study represents a notable step forward in elucidating plasmid diversity and function within soil microbiomes and establishes a foundational framework for exploring their roles in natural environments. Here, the authors report the Global Soil Plasmidome Resource, a comprehensive plasmid soil catalog, that explores the roles of plasmids in microbial adaptation and host integration, highlighting differences between plasmids from cultivated and uncultivated microorganisms and across soil habitats.

BackgroundIn the management of mucosal neoplasm and early cancer, therapeutic gastrointestinal endoscopy evolved from simply polypectomy, endoscopic mucosal resection, endoscopic submucosal dissection (ESD), to endoscopic full thickness resection (EFTR). Full thickness clip closure followed by transmural resection mimics surgical principles. It is safe, effective, and technically less demanding compared to other techniques. Over-the-scope clip (OTSC)-assisted EFTR or OTSC-EFTR enables the endoscopists to manage difficult lesions.MethodsWe video recorded and report our 1-year single center experience of 12 consecutive EFTR cases since the dedicated OTSC-EFTR device was approved in the USA.ResultsWe demonstrate that OTSC-EFTR can be very useful to manage residual neoplastic tissue that cannot be removed during conventional mucosal resection due to deeper invasion, submucosal fibrosis, scaring from prior intervention, and appendiceal involvement. Caution should be used for EFTR of the ileocecal valve lesions.ConclusionWe propose that layered or stacked biopsy of the appendiceal stump after EFTR should be performed to rule out a positive residual base. Due to the limited size of the FTRD resection hood (13 mm internal diameter × 23 mm depth), for larger sessile adenomas in the colon, we propose a hybrid approach for complete removal: piecemeal EMR for tumor debulking followed by OTSC-EFTR to achieve R0 resection. We believe OTSC-EFTR offers safety and efficiency with very high success rate.