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Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.

Background Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs.Methods To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing.Results TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis‐related genes (DRGs) in COPD remain unclear. Methods The expression of DRGs was identified by analyzing RNA sequencing (RNA‐seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co‐expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes. Results We identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke‐induced COPD mouse lung tissues and bronchial epithelial cells (BEAS‐2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate. Conclusion We highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

Abstract Purpose To explore the role and effects of the single-nucleotide polymorphisms (SNPs) of the two functionally related indoleamine 2,3-dioxygenase (IDO) isoforms on IDO activity in the Chinese Han ethnic population. Methods A total of 151 consecutive patients of Chinese Han ethnicity (99 men and 52 women; average age 51.92 ± 18.26 years) with pulmonary TB admitted to Beijing Chest Hospital between July 2016 and February 2017 were enrolled in the study. The serum levels of tryptophan (Trp) and its metabolites, IDO1 and IDO2 mRNA levels, and the relationship of IDO1 and IDO2 SNPs with the serum Kyn/Trp ratio in TB patients and healthy controls were examined by LC/ESI–MS/MS analysis. Genomic DNA was isolated from whole blood, and the PCR products were sequenced and analyzed. Results In Chinese Han participants, only IDO2 had SNPs R248W and Y359X that affected IDO activity, as determined by the serum Kyn/Trp ratio. IDO1 and IDO2 mRNA levels were inversely related in TB patients and healthy controls. Conclusions IDO2 SNPs and the opposite expression pattern of IDO1 and IDO2 affected IDO activity in Chinese Han TB patients.

An increasing number of satellites are currently being launched into orbit to work in the form of clusters or constellations. However, the initial orbit position is accompanied by random errors, which will propagate during their running. Therefore, the orbit precision of the satellites directly affects space safety, network accuracy, and operating efficiency. Hence, accurate and fast random error estimation is essential to improve satellite control. The traditional method will take much time and cost, and it is associated with complex calculations or low accuracy, especially for large-scale constellations. In this paper, a random error evaluation model based on the ellipsoid is proposed. It can be used to estimate initial positions and error propagation for any orbit satellites. By comparing with the experiment results using the Monte Carlo method, it is proved that the proposed model is relatively simple, highly effective, and good at accuracy.

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Constellation-to-ground coverage analysis is an important problem in practical satellite applications. The classical net point method is one of the most commonly used algorithms in resolving this problem, indicating that the computation efficiency significantly depends on the high-precision requirement. On this basis, an improved cell area-based method is proposed in this paper, in which a cell is used as the basic analytical unit. By calculating the accuracy area of a cell that is partly contained by the ground region or partly covered by the constellation, the accurate coverage area can be obtained accordingly. Experiments simulating different types of coverage problems are conducted, and the results reveal the correctness and high efficiency of the proposed analytical method.

ObjectivesBone morphogenetic protein 2 (BMP2) triggers hypertrophic differentiation after chondrogenic differentiation of mesenchymal stem cells (MSCs), which blocked the further application of BMP2-mediated cartilage tissue engineering. Here, we investigated the underlying mechanisms of BMP2-mediated hypertrophic differentiation of MSCs.Materials and MethodsIn vitro and in vivo chondrogenic differentiation models of MSCs were constructed. The expression of H19 in mouse limb was detected by fluorescence in situ hybridization (FISH) analysis. Transgenes BMP2, H19 silencing, and overexpression were expressed by adenoviral vectors. Gene expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemistry. Correlations between H19 expressions and other parameters were calculated with Spearman’s correlation coefficients. The combination of H19 and Runx2 was identified by RNA immunoprecipitation (RIP) analysis.ResultsWe identified that H19 expression level was highest in proliferative zone and decreased gradually from prehypertrophic zone to hypertrophic zone in mouse limbs. With the stimulation of BMP2, the highest expression level of H19 was followed after the peak expression level of Sox9; meanwhile, H19 expression levels were positively correlated with chondrogenic differentiation markers, especially in the late stage of BMP2 stimulation, and negatively correlated with hypertrophic differentiation markers. Our further experiments found that silencing H19 promoted BMP2-triggered hypertrophic differentiation through in vitro and in vivo tests, which indicated the essential role of H19 for maintaining the phenotype of BMP2-induced chondrocytes. In mechanism, we characterized that H19 regulated BMP2-mediated hypertrophic differentiation of MSCs by promoting the phosphorylation of Runx2.ConclusionThese findings suggested that H19 regulates BMP2-induced hypertrophic differentiation of MSCs by promoting the phosphorylation of Runx2.

Background: Meta-analysis is an epidemiological, recognized, quantifiable study design that helps in systematical evaluation of earlier research studies to originate conclusions indicative of the body of research. This paper provides an overview to meta-analysis and to highlight its rationales and also over-all considerations related to meta-analysis. This article emphasizes on methods that are used in order to produce a demanding meta-analysis including various facets of staging and understandings of meta-analysis are deliberated. Methodology: A Systematic literature was conducted from 1990 till 31st December 2017, utilizing PubMed, Web of science, Scopus and Embase using a single keyword "meta-analysis in medicine". We made 5 groups on the basis of years and the variation in the number of articles (meta-analyses) published. Results: One of the critical outcomes of the meta-analysis study result is its heterogeneity or variability examination. Our results showed that the number of meta-analysis published in the recent years has excelled rapidly in comparison to the previous rate i.e. 3294 meta-analyses were published back in 1990-1995, which increased to 7863 in 1996-2000, 18044 for the year 2002-2007, 44965 articles in 2008-2013 and 76135 in 2014-2017. Conclusion: Meta-analysis results in the detailed and accurate assessment of the consequences of various treatments, different risk factors for any particular or specific diseases or some other outcomes, other than individual research contributing to joint analysis. Thoroughly conducted meta-analyses can be a useful tool in evidence-based medicine. The needs of integrating outcomes from several studies confirm that meta-analytic research is necessary and the vast literature based on newly generated researches contribute highly in conduct of this research achievable.

Abstract Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M. tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu province in China were genotyped using large sequence polymorphisms (LSPs) and variable number tandem repeats (VNTR). Ten isolates, which represent major nodes of VNTR-based minimum spanning tree, were selected and subsequently subjected to multi-locus sequence analyses (MLSA) that include 82 genes. Based on a robust lineage assignment, we tested the association between lineages and clinical characteristics by logistic regression. There are three major lineages of M. tuberculosis prevalent in Xinjiang, viz. the East Asian Lineage 2 (42.1%; 56/133), the Euro-American Lineage 4 (33.1%; 44/133), and the Indian and East African Lineage 3 (24.8%; 33/133); two lineages prevalent in Gansu province, which are the Lineage 2 (87%; 47/54) and the Lineage 4 (13%; 7/54). The topological structures of the MLSA-based phylogeny support the LSP-based identification of M. tuberculosis lineages. The statistical results suggest an association between the Lineage 2 and the hemoptysis/bloody sputum symptom, fever in Uygur patients. The pathogenicity of the Lineage 2 remains to be further investigated.

Rationale. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is highly heterogeneous with a plethora of different etiologic factors and inflammatory presentations. COPD with higher blood eosinophil count is associated with increased readmission rates and better corticosteroid responses. However, the clinical features of eosinophilic AECOPD are not well explored. Thus, this study was aimed at exploring the clinical differences between eosinophilic and noneosinophilic AECOPD. Methods. A total of 643 AECOPD patients were enrolled in this multicenter cross-sectional study. Finally, 455 were included, 214 in the normal-eosinophil AECOPD (NEOS-AECOPD) group, 63 in the mild increased-eosinophil AECOPD (MEOS-AECOPD) group, and 138 in the severe increased-eosinophil AECOPD (SEOS-AECOPD) group. Demographic data, underlying diseases, symptoms, and laboratory findings were collected. Multiple logistic regression analysis was performed to identify the independent factors associated with blood eosinophils (EOS). Correlations between blood EOS and its associated independent factors were evaluated. Results. The significant differences in 19 factors, including underlying diseases, clinical symptoms, and laboratory parameters, were identified by univariate analysis. Subsequently, multiple logistic regression analysis revealed that lymphocyte%, neutrophil% (NS%), procalcitonin (PCT), and anion gap (AG) were independently associated with blood EOS in AECOPD. Both blood EOS counts and EOS% were significantly correlated with lymphocyte%, NS%, PCT, and AG. Conclusions. Collectively, blood EOS was independently associated with lymphocyte%, NS%, PCT, and AG in AECOPD patients. Lymphocyte% was lower, and NS%, PCT, and AG were higher in eosinophilic AECOPD. Our results indicate that viral-dominant infections are the probable major etiologies of eosinophilic AECOPD. Noneosinophilic AECOPD is more likely associated with bacterial-dominant infections. The systemic inflammation in noneosinophilic AECOPD was more severe.