Identification of functional elements for a protein of interest is important for achieving a mechanistic understanding. However, it remains cumbersome to assess each and every amino acid of a given ...protein in relevance to its functional significance. Here, we report a strategy, PArsing fragmented DNA Sequences from CRISPR Tiling MUtagenesis Screening (PASTMUS), which provides a streamlined workflow and a bioinformatics pipeline to identify critical amino acids of proteins in their native biological contexts. Using this approach, we map six proteins-three bacterial toxin receptors and three cancer drug targets, and acquire their corresponding functional maps at amino acid resolution.
To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes.
Two children with 17β ...hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children's Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.
The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5:1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respective
AbstractIn general, polymers that enhance the mechanical strength of gypsum plaster simultaneously decrease its water absorption capability. In this research, starting from polyvinyl acetate (PVAc) ...and polyvinyl alcohol (PVA), respectively, two groups of PVA-derived polymers were, partially hydrolyzed polyvinyl acetates (PHPVAs) and polyvinyl alcohol sulfates (PVAS). The modulation of mechanical strength and water absorption of gypsum plaster with PHPVA and PVAS was studied. Their structure–property relationship was investigated. Except for morphology, the influence of product structure on the mechanical properties of the hardened gypsum plaster was studied, including mechanical strengths, dynamic water absorption, hydration degree, and hydration temperature. The mechanical strength initially increased with increasing hydrolysis or sulfonation degree but eventually decreased. The water absorption capability was proportional to the hydrolysis degree but was not significantly related to sulfonation degree. PVAS are the optimum candidate for modeling material, whereas PHPVA is optimal for construction materials. By molecular modification of PVA, highly enhanced mechanical strength can be realized with modulatable water absorption of the hardened gypsum plaster.
ObjectiveTo investigate the effect of whole-process case management based on service process design on patients undergoing total knee arthroplasty (TKA) in areas including pain, function, ...satisfaction, and complications. MethodsA total of 204 patients who underwent unilateral TKA between April 2021 and March 2022 at the Department of Orthopedics, West China Hospital, Sichuan University were enrolled. By using a random number table, the patients were randomly assigned to two groups, 102 in the general case management group (group G) and 102 in the whole-process case management group (group W). Patients in group G received traditional perioperative case management, while those in the whole-process case management group received integrated case management optimized on the basis of the service process design. The two groups of patients were studied through comparison of their general data, Visual Analogue Scale (VAS) pain score, knee flexion and range of motion, Hospital for Special Surgery (HSS) knee score, the
To detect Zika virus more rapidly and accurately, we developed a novel method that utilized a real-time fluorescence reverse transcription loop-mediated isothermal amplification (LAMP) technique. The ...NS5 gene was amplified by a set of six specific primers that recognized six distinct sequences. The amplification process, including 60 min of thermostatic reaction with
Bst
DNA polymerase following real-time fluorescence reverse transcriptase using genomic Zika virus standard strain (MR766), was conducted through fluorescent signaling. Among the six pairs of primers that we designate here, NS5 was the most efficient with a high sensitivity of up to 3.3 ng/μl and reproducible specificity on eight pathogen samples that were used as negative controls. The real-time fluorescence reverse transcription LAMP detection process can be completed within 35 min. Our study demonstrated that real-time fluorescence reverse transcription LAMP could be highly beneficial and convenient clinical application to detect Zika virus due to its high specificity and stability.
During adaptation to host environments, many microorganisms alter their cell surface. One mechanism for doing so is variation in the number of amino acid repeats in cell surface proteins encoded by ...hypermutable DNA tandem repeats. In the yeast Candida albicans, an opportunistic human pathogen, the gene SSR1 encodes a GPI-anchored cell wall protein with a structural role. It contains two regions consisting of tandem repeats, almost exclusively encoding the amino acid pair Ser-Ala. As expected, the repeat regions make SSR1 highly mutable. New SSR1 alleles arose with a frequency of 1.11×10-4 per cell division in serially propagated cells. We also observed a large number (25) of SSR1 alleles with different repeat lengths in a survey of 131 isolates from a global strain collection. C. albicans is diploid, and combinations of these allele generated 41 different SSR1 genotypes. In both repeat regions, nonsynonymous mutations were largely restricted to one particular repeat unit. Two very similar allele combinations were largely restricted to one clade, clade 1. Each combination was present in ~30% of 49 infection-causing clade 1 strains, but one was rare (2%), the other absent in 46 infection-causing strains representing the remainder of the species (P < 0.00018 and 0.00004; Fisher's exact test). These results indicate that both repeat regions are under selection and that amino acid repeat length polymorphisms generate Ssr1 protein variants most suitable for specific genetic backgrounds. One of these two allele combinations was 5.51 times more frequent, the other 1.75 times less frequent in 49 clade 1 strains that caused disease than in 36 commensal clade 1 strains (P = 0.0105; Chi2 test). This indicates that insertion and deletion of repeats not only generates clade-optimized Ssr1p variants, but may also assist in short-term adaptation when C. albicans makes the transition from commensal to pathogen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acupuncture has been increasingly used in patients with chronic pain, yet no bibliometric analysis of acupuncture studies for chronic pain exists.
To investigate the characteristics, hotspots and ...frontiers of global scientific output in acupuncture research for chronic pain over the past decade.
We retrieved publications on acupuncture for chronic pain published from 2011 to 2022 from the Science Citation Index Expanded (SCI-expanded) of the Web of Science Core Collection (WoSCC). The co-occurrence relationships of journals/countries/institutions/authors/keywords were performed using VOSviewer V6.1.2, and CiteSpace V1.6.18 analyzed the clustering and burst analysis of keywords and co-cited references.
A total of 1616 articles were retrieved. The results showed that the number of annual publications on acupuncture for chronic pain has increased over time, with the main types of literature being original articles (1091 articles, 67.5 %) and review articles (351 articles, 21.7 %). China had the most publications (598 articles, 37 %), with Beijing University of Traditional Chinese Medicine (93 articles, 5.8 %) and Evidence-based Complementary and Alternative Medicine ranked first (169 articles, 10.45 %) as the most prolific affiliate and journal, respectively. Liang FR was the most productive author (43 articles), and the article published by Vickers Andrew J in 2012 had the highest number of citations (625 citations). Recently, "acupuncture" and "pain" appeared most frequently. The hot topics in acupuncture for chronic pain based on keywords clustering analysis were experimental design, hot diseases, interventions, and mechanism studies. According to burst analysis, the main research frontiers were functional connectivity (FC), depression, and risk.
This study provides an in-depth perspective on acupuncture for chronic pain
studies, revealing pivotal points, research hotspots, and research trends. Valuable ideas are provided for future research activities.
•This is the first bibliometric article and review about acupuncture for chronic pain.•Two bibliometric analysis software, CiteSpace and VOSviewer, were used to perform the analysis.•The article thoroughly discusses the hotspots and trends in acupuncture for chronic pain, and is an important reference.
The burden of obesity and associated cardiometabolic diseases has been considered as an important risk factor for lupus patients. Therefore, whether obesity is involved in the over-activation of ...autoimmune response has attracted more and more attention. Hydroxychloroquine is a synthetic antimalarial drug and has been the clinical treatment of rheumatic diseases irreplaceable first-line drugs. Hydroxychloroquine has been suggested to have beneficial effects on lipids and insulin sensitivity, which may contribute in lowering high cardiovascular risk in SLE patients. However, its mechanism on insulin sensitivity and lipid disorders is far from being completely understood. In the present study, the therapeutic effects of hydroxychloroquine were evaluated under pathological conditions
. Obesity was induced in C57BL/6 mice fed with high-fed diet, or in mice fed with high-fat diet and hydroxychloroquine. In addition, healthy mice that received normal chow diet were also monitored. The present results revealed that hydroxychloroquine reduced weight, hepatic steatosis, glucose, and insulin resistance. Furthermore, hydroxychloroquine downregulated the expression of peroxisome proliferator-activated receptor gamma in the liver. According to these present results, genes about lipid metabolism went down in high-fat mice liver. Hydroxychloroquine shows potential in ameliorating obesity-induced pathology, which acts though PPARγ to facilitate the healthy function of hepatic tissues. This evidence shows that hydroxychloroquine plays a role in improving obesity-induced lipotoxicity and insulin resistance though the peroxisome proliferator-activated receptor gamma pathway.
Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor that facilitates innate immune signaling. Upon virus infection, the expression of TRIM14 is significantly induced, which stimulates ...the production of type-I IFNs and proinflammatory cytokines. As excessive immune responses lead to harmful consequences, TRIM14-mediated signaling needs to be tightly balanced. In this study, we identify really interesting new gene-type zinc finger protein 125 (RNF125) as a negative regulator of TRIM14 in the innate antiviral immune response. Overexpression of RNF125 inhibits TRIM14-mediated antiviral response, whereas knockdown of RNF125 has the opposite effect. RNF125 interacts with TRIM14 and acts as an E3 ubiquitin ligase that catalyzes TRIM14 ubiquitination. RNF125 promotes K48-linked polyubiquitination of TRIM14 and mediates its degradation via the ubiquitin-proteasome pathway. Consequently, wild-type mouse embryonic fibroblasts show significantly reduced TRIM14 protein levels in late time points of viral infection, whereas TRIM14 protein is retained in RNF125-deficient mouse embryonic fibroblasts. Collectively, our data suggest that RNF125 plays a new role in innate immune response by regulating TRIM14 ubiquitination and degradation.
With the development of the economy and the rapid increase in traffic volume, an overload phenomenon often occurs. This paper studied a vehicle load identification technique based on orthotropic ...bridge deck stress monitoring data. The strain responses on the lower edge of multiple U-ribs were collected under vehicles crossed the deck. Firstly, an index based on the cross-correlation function of strain response between different measurement points on the same U-rib was used to evaluate vehicle speed. Secondly, a cosine similarity index was proposed to locate the transverse position of the vehicle. Finally, the unknown vehicle load was identified on the basis of a calibrated strain response area matrix. The effectiveness and anti-noise performance of the proposed method were verified using numerical simulation. An experimental model was designed and some strain gauges were installed to measure the strain response, and the test was carried out to further verify the algorithm’s performance. Numerical and experimental results show that the proposed method could effectively identify the vehicle load with good anti-noise performance. Moreover, a calibration space was provided to guide practical engineering applications. The proposed method does not damage bridge decks, does not affect traffic, and is economical.
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