Mediating effect of X-26109 on the causal relationship between CD14 CD16 monocyte activation complex and rheumatoid arthritis in Europe.

The regulation of the immune system is crucial in the pathogenesis of various diseases. The direct involvement of immune cells in the development of rheumatoid arthritis (RA) and the potential mediation by metabolites remains to be elucidated. This study utilized a two-step, two-sample Mendelian randomization (MR) approach employing the inverse variance weighted (IVW) method to investigate the causal role of immune cells in RA and to assess the mediation effect of metabolites on the association between immune cells and RA.

Physical unclonable in-memory computing for simultaneous protecting private data and deep learning models.

Compute-in-memory based on resistive random-access memory has emerged as a promising technology for accelerating neural networks on edge devices. It can reduce frequent data transfers and improve energy efficiency. However, the nonvolatile nature of resistive memory raises concerns that stored weights can be easily extracted during computation.

Clinical and economic evaluation of blood culture whole process optimisation in critically ill adult patients with positive blood cultures.

Objectives: Optimising blood culture processing is important to ensure that bloodstream infections are accurately diagnosed while minimising adverse events caused by antibiotic abuse. This study aimed to evaluate the impact of optimised blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures.

Methods: From March 2020 to October 2021, this microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimisation of bottle reception, graded reports and an upgraded laboratory information system.

Carbapenem-resistant Klebsiella pneumoniae capsular types, antibiotic resistance and virulence factors in China: a longitudinal, multi-centre study.

Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat. Here we present a longitudinal analysis of 1,017 CRKP isolates recovered from patients from 40 hospitals across China between 2016 and 2020. Virulence gene and capsule typing revealed expansion of CRKP capsule type KL64 (59.

Miltefosine exhibits fungicidal activity through oxidative stress generation and Aif1 activation in Candida albicans.

Invasive candidiasis is the most common and serious fungal disease worldwide, and the development of antifungal drug resistance in Candida spp. is an emerging problem. Miltefosine, approved as an orphan drug for the therapy of invasive candida infections by the US Food and Drug Administration, has broad-spectrum antifungal activity, but its mechanism of action is unclear.

Observation of the therapeutic effect of auricular bean pressing on early knee osteoarthritis pain: A randomized controlled trial.

Background: In the treatment of knee osteoarthritis (KOA), there is a need for the long-term use of therapeutic drugs that reduce joint pain and have fewer adverse effects.

Objective: This study aimed to investigate the therapeutic effect of bean pressing on ear points on early KOA pain.

Methods: One hundred patients with KOA recruited at the Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022 were divided randomly into a treatment group (n= 50) and control group (n= 50).

The Molecular Epidemiology of Prevalent Klebsiella pneumoniae Strains and Humoral Antibody Responses against Carbapenem-Resistant K. pneumoniae Infections among Pediatric Patients in Shanghai.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has caused wide dissemination among pediatric patients globally and thus has aroused public concern. Here, we investigated the clinical epidemiological characteristics of 140 nonreplicate clinical K. pneumoniae strains isolated from pediatric patients between January and December 2021.

Characterization and Functional Studies of a Novel Depolymerase Against K19-Type .

Carbapenem-resistant (CRKP), a pathogen that causes severe nosocomial infections and yields a high mortality rate, poses a serious threat to global public health due to its high antimicrobial resistance. Bacteriophages encode polysaccharide-degrading enzymes referred to as depolymerases that cleave the capsular polysaccharide (CPS), one of the main virulence factors of . In this study, we identified and characterized a new capsule depolymerase K19-Dpo41 from bacteriophage SH-KP156570.

Multilocus Sequence Typing and Antifungal Susceptibility of Vaginal and Non-vaginal Isolates From China.

is a common cause of infections. In our present study, we investigated the antifungal susceptibility and molecular epidemiology of vaginal and non-vaginal isolates. Seventy-six vaginal strains isolated from patients with vulvovaginal candidiasis and 57 non-vaginal isolates were collected at two hospitals in Shanghai, China.

Establishment of drug screening in human embryonic stem cells based on a high-content screening system.

High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g.

Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates.

is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the susceptibility of 8 drugs against 42 clinical isolates. All isolates showed high MICs to voriconazole (MIC>16 μg/ml), itraconazole (MIC>16 μg/ml), posaconazole (MIC>16 μg/ml), isavuconazole (MIC>16 μg/ml), amphotericin B (MIC>16 μg/ml), and terbinafine (MIC>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC>8 μg/ml), with the exception of miltefosine showing an MIC value of 4 μg/ml.

Antifungal Activity and Mode of Action of Miltefosine Against Clinical Isolates of .

attracts attention from medical professionals mainly for its intrinsic resistance to fluconazole and the limited number of drugs available to treat vulvovaginal candidiasis. Miltefosine was demonstrated to have good antifungal activity both and . Here, we determined the susceptibility profiles of 57 clinical isolates from vulvovaginal candidiasis patients and assessed the antifungal activity of miltefosine against .

Characterization of vaginal microbiota in Chinese women with cervical squamous intra-epithelial neoplasia.

Objectives: Although persistent human papillomavirus (HPV) infection is a major cause of cervical squamous intra-epithelial neoplasia, the relationship between vaginal microbiota and different grades of squamous intra-epithelial neoplasia is not well established. We explored the possible relationship between the vaginal microbiota and the progression of cervical squamous intra-epithelial neoplasia.

Methods: We evaluated 69 women who attended the Obstetrics and Gynecology Hospital of Fudan University.

ERG11 couples oxidative stress adaptation, hyphal elongation and virulence in Candida albicans.

Candida albicans is a major fungal opportunistic pathogen for humans. In the treatment of C. albicans, azole drugs target the sterol 14α-demethylase (CYP51) encoded by ERG11 gene.

Clonal spread and azole-resistant mechanisms of non-susceptible Candida albicans isolates from vulvovaginal candidiasis patients in three Shanghai maternity hospitals.

In our multicenter study, 43 fluconazole non-susceptible and 45 fluconazole-susceptible isolates were collected from vulvovaginal candidiasis (VVC) patients from three Shanghai maternity hospitals to analyze their molecular epidemiological features and fluconazole resistant mechanisms. Cross-resistance to fluconazole, itraconazole and voriconazole was observed in 53.5% of the nonsusceptible isolates.

A newly identified amino acid substitution T123I in the 14α-demethylase (Erg11p) of Candida albicans confers azole resistance.

The increasing prevalence of azole resistance in Candida albicans poses a growing problem for clinical treatment. Amino acid substitution of the 14α-demethylase (Erg11p) encoded by the ERG11 gene is one of the most common mechanisms involved in azole resistance. Although amino acid substitutions of Erg11p have been observed in many clinical isolates, only a few amino acid substitutions have been confirmed to be related to azole resistance.

The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population.

Endothelial NOS (NOS3) has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE). Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population.

Molecular specification and patterning of progenitor cells in the lateral and medial ganglionic eminences.

We characterized intrinsic and extrinsic specification of progenitors in the lateral and medial ganglionic eminences (LGE and MGE). We identified seven genes whose expression is enriched or restricted in either the LGE [biregional cell adhesion molecule-related/downregulated by oncogenes binding protein (Boc), Frizzled homolog 8 (Fzd8), Ankrd43 (ankyrin repeat domain-containing protein 43), and Ikzf1 (Ikaros family zinc finger 1)] or MGE [Map3k12 binding inhibitory protein 1 (Mbip); zinc-finger, SWIM domain containing 5 (Zswim5); and Adamts5 [a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5]]. Boc, Fzd8, Mbip, and Zswim5 are apparently expressed in LGE or MGE progenitors, whereas the remaining three are seen in the postmitotic mantle zone.

Haploinsufficiency for adrenomedullin reduces pinopodes and diminishes uterine receptivity in mice.

Adrenomedullin (AM) is a multifunctional peptide vasodilator that signals through a G-protein-coupled receptor when the receptor, called calcitonin receptor-like receptor (CL), is associated with a receptor activity-modifying protein 2 (RAMP2). We demonstrated previously that haploinsufficieny for each of these genes led to reduced maternal fertility, and that even a modest genetic reduction of AM peptide caused maternal defects in implantation, placentation, and fetal growth. Here, we further demonstrate that Adm(+/-) female mice displayed reduced pregnancy success rates that were not caused by defects in folliculogenesis, ovulation, or fertilization.

Topography of thalamic projections requires attractive and repulsive functions of Netrin-1 in the ventral telencephalon.

Recent studies have demonstrated that the topography of thalamocortical (TC) axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel). However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains.

SOX2 is a dose-dependent regulator of retinal neural progenitor competence.

Approximately 10% of humans with anophthalmia (absent eye) or severe microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, a SOXB1-HMG box transcription factor. However, at present, the molecular or cellular mechanisms responsible for these conditions are poorly understood. Here, we directly assessed the requirement for SOX2 during eye development by generating a gene-dosage allelic series of Sox2 mutations in the mouse.

Coexpression of angiogenic factors in brain arteriovenous malformations.

Objective: Brain arteriovenous malformations (BAVMs) are structurally unstable blood vessels that display an angiogenic phenotype, possibly maintained by concerted effects of key angiogenic factors. Therefore, we hypothesized that there are close correlations among key angiogenic factors in BAVMs and that levels of key angiogenic factors are associated with BAVM clinical characteristics that are linked with vascular instability.

Methods: We measured the expression of angiopoietin-2 (Ang-2), matrix metalloproteinase-9, vascular endothelial growth factor (VEGF), and platelet-derived growth factor-AA and -BB by use of enzyme-linked immunosorbent assay in 27 BAVM surgical specimens.

Regulation of tie2 expression by angiopoietin--potential feedback system.

To study a potential feedback system in the angiopoietin (Ang)-Tie2 system, the authors examined effects of Ang1 and Ang2 on Tie2 expression on human umbilical vein endothelial cells (HUVECs) with or without stimulation by a potent inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Ang1, but not Ang2, down-regulated Tie2 expression on HUVECs without TNF-alpha stimulation. Both Ang1 and Ang2 attenuated TNF-alpha-induced Tie2 up-regulation.