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By further combining with a spatiotemporal controllable photothermal hyperthermia, we demonstrated a near-complete tumor suppression both in vitro (98.6%) and large solid tumors in vivo (96.2%). Moreover, BMH hydrogel could significantly promote the MDR-infected wound healing in vivo by efficiently eradicating bacterial invasion and perpetually ameliorating the oxidative and inflammatory wound microenvironment. Collectively, BMH hydrogel indicated great therapeutic potentials for both cancer therapy and tissue engineering.

Fever is a very common reason for emergency consultation during pregnancy, and may be associated with maternal, obstetrical and/or fetal adverse outcomes. The aim of this study was to determine the etiologies and to analyze the maternal or fetal complications of fever in pregnancy.

A retrospective single center study including all patients who consulted for fever above 38 °C during pregnancy in the gynecological emergency ward from August 2016 to July 2017.

A total of 100 pregnant women who consulted for fever were included. The etiologies were common viral infections (37 %), influenza (21 %), pyelonephritis (11 %), viral gastroenteritis (6%), chorioamnionitis (5%), other (5%). The etiology was unknown for 15 %. Fever was confirmed during consultation in 45/100 patients (45 %). Among patients with confirmed fever, 21/45 (47 %) were hospitalized with a median stay of 3 days [IQR 2-4] and 10/45(22 %) developed fetal or maternal complications. Probabilistic antibiotics were delivered for 34/45, 76 % patiended to target patients at risk of complications in an optimal way and to study new management strategies.Autism spectrum disorder is a neurodevelopmental disorder (NDD) with complex genetic architecture marked primarily by social and communication impairments along with deficits in restrictive and repetitive behaviors. Due to the complex nature and genetic heterogeneity of the disease, genotype and phenotype correlation remains challenging. Prior studies have implicated RALGAPB as a candidate gene for ASD, but stringent analysis is required to determine the pathogenicity. By targeted sequencing, we identified a new de novo RALGAPB missense variant (c.1238C> T; p.T413M) in an ASD family. By leveraging published large-scale genome sequencing studies, we curated five de novo likely gene-disruptive (LGD) variants and 5 de novo missense variants in ASD and related NDDs and revealed a genome-wide significant excess of RALGAPB de novo LGD variants (P_adjust = 0.0053). Quantitative reverse transcription PCR revealed that the frameshift variant c.1927dupA; p.N643fs*3 reduced mRNA expression levels confirming the loss-of-function effect. Co-expression analysis using human brain transcriptome data provide the potential functional link of RALGAPB and 38 ASD and/or NDD genes. Our study suggests RALGAPB as a new NDD risk gene which should be considered in clinical diagnosis of ASD and related NDDs.DNA methylation on cytosine in CpG islands generates 5-methylcytosine (5mC), and further modification of 5mC can result in the oxidized variants 5-hydroxymethyl (5hmC), 5-formyl (5fC), and 5-carboxy (5caC). Base excision repair (BER) is crucial for both genome maintenance and active DNA demethylation of modified cytosine products and involves substrate-product channeling from nucleotide insertion by DNA polymerase (pol) β to the subsequent ligation step. read more Here, we report that, in contrast to the pol β mismatch insertion products (dCTP, dATP, and dTTP), the nicked products after pol β dGTP insertion can be ligated by DNA ligase I or DNA ligase III/XRCC1 complex when a 5mC oxidation modification is present opposite in the template position in vitro. A Pol β K280A mutation, which perturbates the stabilization of these base modifications within the active site, hinders the BER ligases. Moreover, the nicked repair intermediates that mimic pol β mismatch insertion products, i.e., with 3'-preinserted dGMP or dTMP opposite templating 5hmC, 5fC or 5caC, can be efficiently ligated, whereas preinserted 3'-dAMP or dCMP mismatches result in failed ligation reactions. These findings herein contribute to our understanding of the insertion tendencies of pol β opposite different cytosine base forms, the ligation properties of DNA ligase I and DNA ligase III/XRCC1 complex in the context of gapped and nicked damage-containing repair intermediates, and the efficiency and fidelity of substrate channeling during the final steps of BER in situations involving oxidative 5mC base modifications in the template strand.Ataxia Telangiectasia and Rad3-Related kinase (ATR) is a master regulator of genome maintenance, and participates in DNA replication and various DNA repair pathways. In a genome-wide screen for ATR-dependent fitness genes, we identified a previously uncharacterized gene, C17orf53, whose loss led to hypersensitivity to ATR inhibition. C17orf53 is conserved in vertebrates and is required for efficient cell proliferation. Loss of C17orf53 slowed down DNA replication and led to pronounced interstrand crosslink (ICL) repair defect. We showed that C17orf53 is a ssDNA- and RPA-binding protein and both characteristics are important for its functions in the cell. In addition, using multiple omics methods, we found that C17orf53 works with MCM8/9 to promote cell survival in response to ICL lesions. Taken together, our data suggest that C17orf53 is a novel component involved in ICL repair pathway.

Fatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time.

Fifty-five consecutive de novo PD patients (age 64.71±7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up.

Prevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy.