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"He, Cong"
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Integrated single-cell and spatial transcriptomics reveals heterogeneity of fibroblast and pivotal genes in psoriasis
Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis.
Journal Article
Impacts of Helicobacter pylori infection and eradication on gastrointestinal microbiota: An up-to-date critical review and future perspectives
Abstract
Helicobacter pylori (H. pylori) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori-associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori may provide potential targets for H. pylori-related gastric diseases and extragastric manifestations.
Journal Article
Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice
BackgroundThe gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.MethodsWe collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.ResultsThe structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia–Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.ConclusionsThis study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.
Journal Article
Unusual solute segregation phenomenon in coherent twin boundaries
Interface segregation of solute atoms has a profound effect on properties of engineering alloys. The occurrence of solute segregation in coherent twin boundaries (CTBs) in Mg alloys is commonly considered to be induced by atomic size effect where solute atoms larger than Mg take extension sites and those smaller ones take compression sites in CTBs. Here we report an unusual solute segregation phenomenon in a group of Mg alloys—solute atoms larger than Mg unexpectedly segregate to compression sites of {10
1
¯
1} fully coherent twin boundary and do not segregate to the extension or compression site of {10
1
¯
2} fully coherent twin boundary. We propose that such segregation is dominated by chemical bonding (coordination and solute electronic configuration) rather than elastic strain minimization. We further demonstrate that the chemical bonding factor can also predict the solute segregation phenomena reported previously. Our findings advance the atomic-level understanding of the role of electronic structure in solute segregation in fully coherent twin boundaries, and more broadly grain boundaries, in Mg alloys. They are likely to provide insights into interface boundaries in other metals and alloys of different structures.
Segregation of solute atoms at interfaces affects the properties of alloys and needs to be understood to allow their rational design. Here the authors report an unusual solute segregation phenomenon in a group of Mg alloys, driven by chemical bonding, where solute atoms larger than Mg segregate to compression sites of specific fully coherent twin boundary.
Journal Article
Incidence of periprosthetic joint infection after primary total hip arthroplasty is underestimated: a synthesis of meta-analysis and bibliometric analysis
The American Musculoskeletal Society updated the diagnostic criteria for periprosthetic joint infection (PJI) in 2011 and 2018. However, the overall incidence of PJI since the introduction of these new standards has not been assessed. In order to fill this knowledge gap, a single-group meta-analysis was conducted using articles obtained from several databases, focusing on the incidence of PJI after primary total hip arthroplasty (THA). Our study revealed a significant difference in the incidence of PJI reported by different national or regional databases. Moreover, most cases of PJI were found to be underestimated. This highlights the crucial need for standardized diagnostic criteria and monitoring methods to accurately identify and track cases of PJI. Furthermore, a bibliometric analysis was conducted to provide a comprehensive overview of the current state of research on PJI after THA. This analysis explored the most productive countries, organizations, journals, and individuals in this research area. Additionally, it identified the research trends and hotspots of the last decade, highlighting the advancements and areas of focus in this field. By conducting these analyses, the study aims to contribute to the understanding of PJI after THA and provide valuable insights for clinicians, researchers, and policymakers involved in the management of this condition.
Journal Article
Nontuberculous mycobacteria in China: incidence and antimicrobial resistance spectrum from a nationwide survey
Background
Information on the prevalence and resistance spectrum of nontuberculous mycobacteria (NTM) in China is mainly based on regional or local data. To estimate the proportion of NTM cases in China, a national survey of NTM pulmonary disease was carried out based on acid-fast positive sputum samples collected in 2013.
Methods
Sputum samples collected from enrolled presumptive cases in 72 nationwide tuberculosis surveillance sites from the 31 provinces in the mainland of China were cultured using L-J medium at the National tuberculosis reference laboratory (NTRL). MALDI-TOF MS identified the species of re-cultured strains, and minimal inhibitory concentrations (MICs) were determined to evaluate the drug susceptibility of NTM isolates. Data analysis used statistical software SPSS version 22.0 for Windows statistical package.
Results
Of 4917 mycobacterial isolates cultured, 6.4% [317/4917, 95% confidence interval (
CI
) 5.8%–7.2%] were confirmed as NTM, among which 7.7% (287/3709, 95%
CI
6.9%–8.6%) were from the southern region. In inland and coastal China, 87.7% (95%
CI
78.7%–93.2%) and 50.0% (95%
CI
43.7%–56.3%) of isolates, respectively, were slow-growing mycobacteria (SGM), with the remaining rapid growing mycobacteria (RGM). A total of 29 species were detected,
Mycobacterium abscessus
had higher clarithromycin-inducible resistance rates than
M. massiliense
(65.67% vs 2.22%).
M. kansasii
presented lower resistance rates in linezolid and moxifloxacin than
M. avium-intracellulare
complex (3.23% vs 66.67%, 0 vs 47.22%) and other SGM (3.23% vs 38%, 0 vs 26%).
Conclusions
More NTM pulmonary disease was observed in the south and coastal China (
P
< 0.01). SGM was widely distributed, and more RGM are present in southern and coastal China (
P
< 0.01). The antimicrobial resistance spectrum of different NTM species was significantly different and accurate species identification would be facilitated to NTM pulmonary disease treatment.
Journal Article
The dual role of microglia in Alzheimer’s disease: from immune regulation to pathological progression
Alzheimer’s disease (AD) is a widespread neurodegenerative disorder and one of the major challenges for public health. Despite extensive research, the role of microglia in AD remains complex and dual. The aim of this review is to summarize the most recent advances in research regarding the dual role of microglia in AD concerning both immunomodulation and pathological progression by considering mechanisms of activation of microglia, effects on Aβ clearance, tau pathology, and impacts due to genetic variations on microglial functions. Among these findings are the dual role of microglia, the status of activation for M1 and M2 phenotypes, and the crucial role that genetic variants like TREM2 have in modulating the response of microglia. This review describes how modulation of the microglial signaling pathway might be exploited therapeutically for AD treatment and underlines the relevance of a personalized medicine approach.
Journal Article
An Improved Large Neighborhood Search Algorithm for the Comprehensive Container Drayage Problem with Diverse Transport Requests
Container drayage, as a pivotal element of door-to-door intermodal transportation, has garnered increasing attention due to its significant influence on container logistics costs. Although various types of transport requests have been defined in the literature, no comprehensive study has addressed all of them together yet, due to the lack of an efficient model and corresponding algorithms. Furthermore, existing research on container drayage often neglects the simultaneous incorporation of two trucking operation modes, two empty container repositioning strategies, and the availability of empty containers across multiple depots. To address these issues, this study proposes a comprehensive container drayage problem (CDP) and mathematically formulates it as an innovative mixed integer linear programming (MILP) model, capturing the uncertainty and unpredictability inherent in empty container allocation, truck dispatching, and route planning. Given the problem’s complexity, obtaining an exact solution for large instances is not feasible. Therefore, an improved large neighborhood search (LNS) algorithm is tailored by incorporating the “Sequential insertion” and the “Solution re-optimization” operations. Extensive numerical experiments using randomly generated instances of varying scales validate the correctness of the proposed model and demonstrate the performance of the proposed algorithm. Additionally, sensitivity analysis on the number and distribution of depots and empty containers offers valuable managerial insights for the development of an effective container drayage system.
Journal Article
Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis
The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.
Journal Article