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关键词： enteroviruses   differential receptor usage   cryo-EM   attachment or uncoating   entry  

摘要： Receptor usage defines cell tropism and contributes to cell entry and infection. Coxsackievirus B (CVB) engages coxsackievirus and adenovirus receptor (CAR), and selectively utilizes the decay=accelerating factor (DAF;CD55) to infect cells. However, the differential receptor usage mechanism for CVB remains elusive. This study identified VP3-234 residues (234Q/N/V/D/E) as critical population selection determinants during CVB3 virus evolution, contributing to diverse binding affinities to CD55. Cryoelectron microscopy (cryo-EM) structures of CD55-binding/nonbinding isolates and their complexes with CD55 or CAR were obtained under both neutral and acidic conditions, and the molecular mechanism of VP3-234 residues determining CD55 affinity/specificity for naturally occurring CVB3 strains was elucidated. Structural and biochemical studies in vitro revealed the dynamic entry process of CVB3 and the function of the uncoating receptor CAR with different pH preferences. This work provides detailed insight into the molecular mechanism of CVB infection and contributes to an in-depth understanding of enterovirus attachment receptor usage.

关键词： scRNA-seq   IDEAS   Differential expression  

摘要： We consider an increasingly popular study design where single-cell RNA-seq data are collected from multiple individuals and the question of interest is to find genes that are differentially expressed between two groups of individuals. Towards this end, we propose a statistical method named IDEAS (individual level differential expression analysis for scRNA-seq). For each gene, IDEAS summarizes its expression in each individual by a distribution and then assesses whether these individual-specific distributions are different between two groups of individuals. We apply IDEAS to assess gene expression differences of autism patients versus controls and COVID-19 patients with mild versus severe symptoms.

关键词： phi-Hilfer fractional derivative   controllability results   impulses   integro-differential inclusions   fixed point theorem   coupled system   nonlocal integral conditions  

摘要： This paper studies the controllability of a coupled system for a class of impulsive fractional integro-differential inclusions involving phi-Hilfer fractional derivative and subject to coupled nonlocal integral initial conditions in the case of convex set-valued maps. Some auxiliary conditions are introduced in order to apply a fixed point theorem due to Bohnenblust-Karlin. An illustrative example is provided to exemplify our theoretical results.

关键词： Iron   Fungi   Peptides and proteins   Genetics   Metabolism  

摘要： Ferrichromes are a family of fungal siderophores with cyclic hexapeptide structures. Most fungi produce one or two ferrichrome-type siderophores. Acremonium persicinum MF-347833 produces ferrichrome-like potent Trojan horse antifungal antibiotics ASP2397 and AS2488053, the aluminum- and iron-chelating forms of AS2488059, respectively. Here, we show by gene sequencing followed by gene deletion experiments that A. persicinum MF-347833 possesses two nonribosomal peptide synthetase genes responsible for AS2488059 and ferricrocin assembly. AS2488059 was produced under iron starvation conditions and excreted into the media to serve as a defense metabolite and probably an iron courier. In contrast, ferricrocin was produced under iron-replete conditions and retained inside the cells, likely serving as an iron-sequestering molecule. Notably, the phylogenetic analyses suggest the different evolutionary origin of AS2488059 from that of conventional ferrichrome-type siderophores. Harnessing two ferrichrome-type siderophores with distinct biological properties may give A. persicinum a competitive advantage for surviving the natural environment.

关键词： Crustal imaging   Seismic anisotropy   Crustal structure  

摘要： Crustal anisotropy parameters beneath the Qinling Orogenic Belt (QOB) and its surrounding areas (including the northeastern Tibetan Plateau) are investigated by harmonic fitting the arrival times of the P-to-S converted phase from the Moho and an intracrustal discontinuity. The measurements reveal strong and spatially varying crustal anisotropy beneath the study region, with an average splitting time of 0.50 +/- 0.17 s. The eastern Kunlun Orogen (EKLO), western part of QOB (WWQL) and Longmenshan block (LMB) present relatively larger crustal anisotropy, and the fast orientations changed gradually from NWW-SEE in EKLO and WWQL to NEE-SWW in LMB. The crustal anisotropy measurements, combined with the results from ambient-noise tomography and gravity inversion, suggest that the middle-lower crustal flow induced by the inhomogeneous crustal thickening during the early stage of plateau growth exists beneath these areas. The fast orientations beneath the eastern part of the QOB are predominantly NNE-SSW, nearly orthogonal to that from local shear wave splitting and teleseismic XKS splitting. The crustal anisotropy measurements suggest a layered deformation beneath the eastern QOB. The upper crust retains the fossil deformation formed during the main orogeny, the middle-to-lower crust is dominated by the N-S oriented subduction, collision and continued convergence between the North China Block, South China Block and Qinling microblocks;the upper mantle is decoupled from the crust and mainly controlled by the mantle flow from the Tibetan Plateau.

关键词： Joint infection   Microorganism   Total hip arthroplasty   Direct anterior approach   Lateral approach  

摘要： Background In recent years, total hip arthroplasty via the direct anterior approach (DAA) has become more common. Little is known on the influence of the surgical approach on the microbiological spectrum and resistance pattern in periprosthetic hip joint infections. The aim of the present study was to evaluate the microbiological spectrum and resistance pattern in periprosthetic hip joint infections comparing the direct anterior versus lateral approach in a matched-cohort analysis at a single institution. Methods Patients who underwent revision hip arthroplasty due to PJI following primary total hip arthroplasty with culture positive microbiology were analyzed. In all study patients, both the primary surgery and the revisions surgery were performed at the same institution. Only patients in whom primary surgery was performed via a direct anterior or lateral approach were included (n = 87). A matched cohort analysis was performed to compare the microbiological spectrum and resistance pattern in PJI following direct anterior (n = 36) versus lateral (n = 36) primary THA. Results We identified both a significantly different microbiological spectrum and resistance pattern in PJI comparing direct anterior versus lateral approach THA. Cutibacterium avidum was obtained more frequently in the anterior subgroup (22.2% vs. 2.8%, p = 0.028). In the subgroup of infections with Staphylococcus aureus (n = 12), methicillin resistance was detected in 3/5 cases in the direct anterior group versus 0/7 cases in the lateral group (p = 0.045). Overall, Staphylococcus epidermidis was the most common causative microorganism in both groups (direct anterior: 36.1%;lateral: 27.8%, p = 0.448). Conclusion The present study indicates a potential influence of the localization of the skin incision in THA on the microbiological spectrum and resistance pattern in PJI. Cutibacterium avidum seemed to be a more common causative microorganism in PJI in patients who underwent direct anterior compared to l