Study on the Inhibitory Effects of Ephedra Aconite Asarum

Dendritic cells (DCs) can secrete cytokines stimulated by lipopolysaccharide (LPS), which leads to not just acute inflammatory responses but also Th1 polarization. Furtherly, chronic inflammation or autoimmune diseases could be triggered. As a classic Traditional Chinese Medicine formula, Ephedra Aconite Asarum Decoction with the main ingredients of ephedrine and hypaconitine can show effect on anti-inflammation and immunoregulation. But it remains unclear whether Ephedra Aconite Asarum Decoction controls DCs. In this study, we investigated the effects of Ephedra Aconite Asarum Decoction on LPS-induced bone marrow-derived DCs (BMDCs) in vitro. We found that Ephedra Aconite Asarum Decoction lowered surface costimulators on DCs and reduced the expression of Th1 type cytokines. Yet it is slightly beneficial for shifting to Th2. Our work reveals that the Ephedra Aconite Asarum Decoction can regulate Th1 inflammation through intervening DCs

The satisfaction of elderly people with elderly caring social organizations and its relationship with social support and anxiety during the COVID-19 pandemic: a cross-sectional study

Background: With the deepening of China’s aging population, higher demands have been placed on the supply of elderly care services. As one of the main sources of providing elderly care services, the quality of service provided by elderly caring social organizations (SOs) directly affects the quality of life of the elderly. In recent years, mental health issues among the elderly have become increasingly prominent, especially with the onset of the COVID-19 pandemic. Necessitating the need to pay much more attention to the social support and mental health of this population. This study, therefore, explores the mediating role of institutional satisfaction between the social support and anxiety levels of elderly people in Chongqing’s elderly caring SOs. Method: This study employed a multi-stage stratified random sampling method to survey 1004 service recipients in elderly caring social organizations from July to August 2022. The self-made sociodemographic questionnaire, institutional satisfaction questionnaire, MSPSS, and GAD-7 were used to collect data on sociodemographic characteristics, institutional satisfaction, social support, and anxiety levels of older adults. Exploratory Factor Analysis and Cronbach’s alpha were used to test construct validity and scale reliability, respectively. Data features were described with One-Way Analysis of Variance, while Multiple Linear Regression and Structural Equation Modeling were used to evaluate relationships between social support, institutional satisfaction, and anxiety levels. Results: The average institutional satisfaction score for elderly people in elderly caring SOs was 48.14 ± 6.75. Specifically, the satisfaction score for environmental quality and the satisfaction score for service quality were 16.63 ± 2.56 and 31.52 ± 4.76, respectively. In terms of socio-demographic variables, the presence of visits from relatives, personal annual average income, and self-rated health status all have significant effects on anxiety. Elders who receive visits from relatives have lower levels of anxiety compared to those who do not. Personal annual average income and self-rated health status are negatively correlated with anxiety levels. Social support had significant positive effect on institutional satisfaction, while institutional satisfaction had significant negative effect on anxiety. Institutional satisfaction partially mediated the relationship between social support and anxiety. Conclusions: Our research demonstrates that improving the quality of organizational services in elderly caring SOs and increasing institutional satisfaction among the elders has significant potential for reducing anxiety levels among the elderly. Additionally, the social support by visits from family members cannot be overlooked. We encourage increasing the frequency of family visits through various means to enhance the support provided to elderly individuals

Mediation role of anxiety on social support and depression among diabetic patients in elderly caring social organizations in China during COVID-19 pandemic: a cross-sectional study

Background: Diabetes has become a prominent global public health problem, which is an important cause of death, disease burden, and medical and health economic burden. Previous studies have reported that majority of persons diagnosed with diabetes later presented with psychological and mental health diseases. The study aimed to explore the mediation role of anxiety on social support and depression among diabetic patents in elderly caring social organizations (SOs). Methods: A multi-stage stratified cluster random sampling method was used in this cross-sectional study, and a questionnaire consisting of demographic questionnaire, MSPSS, GAD-7, and CES-D-10 was utilized to gather data. SPSS 22.0 and MPLUS 7.4 were used for statistical analysis. Spearman correlation analysis was employed to investigate correlations of key variables. A generalized linear model was used to exam factors associated with depression. Finally, the mediation effect among study variables was investigated by structural equation modeling (SEM). Results: The average scores of social support, anxiety, and depression were 58.41 ± 14.67, 2.95 ± 3.95, and 7.24 ± 5.53, respectively. The factors of gender, social support, and anxiety were identified as significantly influential factors related to depression among diabetic patients in elderly caring SOs. The effect of social support on depression was significantly mediated by anxiety (β = -0.467, 95%CI: -0.813 to -0.251). Furthermore, anxiety partially mediated the relationship between family support and depression (β = -0.112, 95%CI: -0.229 to -0.012), and anxiety functioned as a complete mediator in the effect of significant others' support and depression (β = -0.135, 95%CI: -0.282 to -0.024). Conclusions: The indirect effect of social support on depression through anxiety among diabetic patients in elderly caring SOs was elucidated. Social support played a key role in maintaining and regulating their mental health, particularly from family and significant others. Social support provided by both family and significant others exerted an important influence on maintaining and regulating their mental health. In light of this pathway, the elderly caring SOs should enhance the magnitude of social support from these two sources, thereby diminishing the likelihood of experiencing anxiety and depression

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort

Objectives: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. Methods: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-β2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. Results: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ± 3.3 vs. 6 ± 3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ± 3.9; p<0.05). Conclusions: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS

Role of the ISKpn element in mediating mgrB gene mutations in ST11 hypervirulent colistin-resistant Klebsiella pneumoniae

BackgroundColistin has emerged as a last-resort therapeutic against antibiotic-resistant bacterial infections, particularly those attributed to carbapenem-resistant Enterobacteriaceae (CRE) like CRKP. Yet, alarmingly, approximately 45% of multidrug-resistant Klebsiella pneumoniae strains now manifest resistance to colistin. Through our study, we discerned that the synergy between carbapenemase and IS elements amplifies resistance in Klebsiella pneumoniae, thereby narrowing the existing therapeutic avenues. This underscores the instrumental role of IS elements in enhancing colistin resistance through mgrB disruption.MethodsFrom 2021 to 2023, 127 colistin-resistant Klebsiella pneumoniae isolates underwent meticulous examination. We embarked on an exhaustive genetic probe, targeting genes associated with both plasmid-mediated mobile resistance-encompassing blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48-like, and mcr-1 to mcr-8-and chromosome-mediated resistance systems, including PhoP/Q, PmrA/B, and mgrB. PCR amplification revealed the presence of virulence-associated genes from the pLVPK plasmid, such as rmpA, rmpA2, iucA, iroB, and peg344. mgrB sequencing was delegated to Sangon Biotech, Shanghai, and the sequences procured were validated using BLAST. Our search for IS elements was navigated through the IS finder portal. Phenotypically, we harnessed broth microdilution (BMD) to ascertain the MICs of colistin. To sketch the clonal lineage of mgrB-mutated CoR-Kp isolates, sophisticated methodologies like MLST and PFGE were deployed. S1-PFGE unraveled the intrinsic plasmids in these isolates. Our battery of virulence assessment techniques ranged from the string test and capsular serotyping to the serum killing assay and the Galleria mellonella larval infection model.ResultsAmong the 127 analyzed isolates, 20 showed an enlarged mgrB PCR amplicon compared to wild-type strains. These emerged over a three-year period: three in 2021, thirteen in 2022, and four in 2023. Antimicrobial susceptibility tests revealed that these isolates consistently resisted several drugs, notably TCC, TZP, CAZ, and COL. Additionally, 85% resisted both DOX and TOB. The MICs for colistin across these strains ranged between 16 to 64 mg/L, with a median of 40 mg/L. From a genetic perspective, MLST unanimously categorized these mgrB-mutated CoR-hvKp isolates as ST11. PFGE further delineated them into six distinct clusters, with clusters A and D being predominant. This distribution suggests potential horizontal and clonal genetic transmission. Intriguingly, every mgrB-mutated CoR-hvKP isolate possessed at least two virulence genes akin to the pLVPK-like virulence plasmid, with iroB and rmpA2 standing out. Their virulence was empirically validated both in vitro and in vivo. A pivotal discovery was the identification of three distinct insertion sequence (IS) elements within or near the mgrB gene. These were:ISKpn26 in eleven isolates, mainly in cluster A, with various insertion sites including +74, +125, and an upstream −35.ISKpn14 in four isolates with insertions at +93, −35, and two upstream at −60.IS903B present in five isolates, marking positions like +74, +125, +116, and −35 in the promoter region. These diverse insertions, spanning six unique locations in or near the mgrB gene, underscore its remarkable adaptability.ConclusionOur exploration spotlights the ISKpn element’s paramount role in fostering mgrB gene mutations in ST11 hypervirulent colistin-resistant Klebsiella pneumoniae. Employing MLST and PFGE, we unearthed two primary genetic conduits: clonal and horizontal. A striking observation was the ubiquitous presence of the KPC carbapenemase gene in all the evaluated ST11 hypervirulent colistin-resistant Klebsiella pneumoniae strains, with a majority also harboring the NDM gene. The myriad mgrB gene insertion locales accentuate its flexibility and the overarching influence of IS elements, notably the pervasive IS5-like variants ISKpn26 and IS903B. Our revelations illuminate the escalating role of IS elements in antibiotic resistance within ST11 hypervirulent colistin-resistant Klebsiella pneumoniae, advocating for innovative interventions to counteract these burgeoning resistance paradigms given their profound ramifications for prevailing treatment modalities

Geochemical reactions altering the mineralogical and multiscale pore characteristics of uranium-bearing reservoirs during CO2 + O2in situ leaching

CO2 + O2in situ leaching has been extensively applied in uranium recovery in sandstone-type uranium deposits of China. The geochemical processes impact and constrain the leaching reaction and leaching solution migration; thus, it is necessary to study the CO2 + O2–water–rock geochemical reaction process and its influence on the physical properties of uranium-bearing reservoirs. In this work, a CO2 + O2–water–rock geochemical reaction simulation experiment was carried out, and the mineralogical and multiscale pore characteristics of typical samples before and after this simulation experiment were compared by X-ray diffraction and high-pressure mercury intrusion porosimetry (HPMIP). The results show that the CO2 + O2–water–rock geochemical reaction has complicated effects on the mineral compositions due to the various reaction modes and types. After the CO2 + O2–water–rock geochemical reaction, the femic minerals decrease and the clay minerals in the coarse sandstone, medium sandstone, fine sandstone, and siltstone increase, while the femic minerals and clay minerals in sandy mudstone show a contrary changing trend. The CO2 + O2–water–rock geochemical reaction decreases the total pore volume of uranium-bearing reservoirs and then promotes pore transformation from small scale to large scale. The fractal dimensions of macropores are decreased, and the fractal dimensions of mesopores, transition pores, and micropores are increased. The effects of felsic mineral and carbonate dissolution, secondary mineral precipitate, clay mineral swelling, and mineral particle migration are simultaneously present in the CO2 + O2in situ leaching process, which exhibit the positive transformation and the negative transformation for the uranium-bearing reservoirs. The mineral dissolution may improve reservoir permeability to a certain degree, while the siltation effect will gradually reveal with the extension of CO2 + O2in situ leaching. This research will provide a deep understanding of the physical property response of uranium-bearing reservoirs during CO2 + O2in situ leaching and indicate the direction for the efficient recovery of uranium resources

MINIMAL PANELS OF RNA MARKERS FOR CELL TYPES USING SINGLE-CELL DATA

Single-cell RNA sequencing technologies provide measurements of the number of RNA molecules in many thousands of individual cells, a rich source of information for determining attributes of cell populations, such as cell types and the variation in gene expression from cell to cell, which are not available from bulk RNA sequencing data [1–5]. A core challenge in the analysis of sc-RNA seq data is to find “marker genes” for some class of cells, e.g., cell type. Another challenge is to describe, let alone quantify, how the individual marker genes cooperate to determine cell labels. Generally, most existing methods of scRNA-seq analysis are at the univariate (single gene) level even though the relevant biology is often decidedly multivariate. In this thesis we introduces a method that formulates marker gene selection as a variation of the well-known “minimal set-covering problem” in combinatorial optimization. Here, the “covering” elements are genes and the objects to be covered are a sub-population of cells with a particular label k. In order to draw this link between marker panels and set coverings, we binarize the raw mRNA counts into “expressed” (positive count) or “not expressed” (zero count). The resulting paradigm, based on covering a target class, differs fundamentally from most standard approaches, in which optimal panels are determined by optimizing their weights with a fixed panel size. In addition to enabling the link to set covering, binarization facilitates the biological interpretation of marker genes and the manner in which they characterize and discriminate among types of cells. Using the covering paradigm, we can predict cell types or transfer marker panels to identify shared cellular processes across data sets in related biological contexts using extremely transparent discriminants, such as the number of expressed panel genes. We illustrate this new methodology in the context of neocortical neurogenesis during mid-gestation when the vast majority of neurons in the brain are produced. To further investigate some basic properties of covering marker panels, we also discuss the stability of covering marker sets, as well as the gene interactions within a marker set. Some generalizations and extensions of the covering algorithm are also introduced. We also present a semi-supervised learning version of marker panel construction when cell labeling is incomplete or some marker genes are known. Finally, we introduce a marker panel based on pairs of genes which characterizes the transitions between cell states