Isolation, identification and complete genome sequence analysis of a strain of foot-and-mouth disease virus serotype Asia1 from pigs in southwest of China

Abstract Backgroud Foot-and-mouth disease virus (FMDV) serotype Asia1 generally infects cattle and sheep, while its infection of pigs is rarely reported. In 2005-2007, FMD outbreaks caused by Asia1 type occurred in many regions of China, as well as some parts of East Asia countries. During the outbreaks, there was not any report that pigs were found to be clinically infected. Results In this study, a strain of FMDV that isolated from pigs was identified as serotype Asia1, and designated as "Asia1/WHN/CHA/06". To investigate the genomic feature of the strain, complete genome of Asia1/WHN/CHA/06 was sequenced and compared with sequences of other FMDVs by phylogenetic and recombination analysis. The complete genome of Asia1/WHN/CHA/06 was 8161 nucleotides (nt) in length, and was closer to JS/CHA/05 than to all other strains. Potential recombination events associated with Asia1/WHN/CHA/06 were found between JS/CHA/05 and HNK/CHA/05 strains with partial 3B and 3C fragments. Conclusion This is the first report of the isolation and identification of a strain of FMDV type Asia1 from naturally infected pigs. The Asia1/WHN/CHA/06 strain may evolve from the recombination of JS/CHA/05 and HNK/CHA/05 strains.</p

Self⁃evaluation and analysis of influencing factors of clinical research knowledge among clinical research coordinators/associates

Objective To understand the self-evaluation of clinical research knowledge among clinical research coordinators（CRC）and clinical research associates（CRA），and to explore their influencing factors，in order to provide reference for conducting high-quality CRC/CRA training. Methods A multi-stage cluster sampling method was employed to select 400 CRC/CRA from four municipal hospitals in Shanghai as study participants. From October to December 2023，data were collected via an online questionnaire（Questionnaire Star）using a self-designed survey covering basic information，self-assessed knowledge of clinical research，and training needs. Statistical analysis was performed on the collected data.Results A total of 378 valid questionnaires were collected，including 187 from CRC and 191 from CRA. Significant differences were observed between CRC and CRA groups in gender，age，education level，major，and years of experience（PPPConclusion CRC and CRA exhibit suboptimal familiarity with clinical research knowledge. As key contributors to clinical research，it is essential to establish unified qualification standards，develop a comprehensive knowledge training system，and enhance their competency to ensure the quality of clinical research

Off-Design Behavior Analysis and Operating Curve Design of Marine Intercooled Gas Turbine

The intercooled gas turbine obtained by adopting an indirect heat exchanger into an existing gas turbine is one of the candidates for developing high-power marine power units. To simplify such a strong coupled nonlinear system reasonably, the feasibility and availability of qualifying equivalent effectiveness as the only parameter to evaluate the intercooler behavior are investigated. Regarding equivalent effectiveness as an additional degree of freedom, the steady state model of a marine intercooled gas turbine is developed and its off-design performance is analyzed. With comprehensive considerations given to various phase missions of ships, operational flexibility, mechanical constraints, and thermal constraints, the operating curve of the intercooled gas turbine is optimized based on graphical method in three-dimensional performance space. The resulting operating curve revealed that the control strategy at the steady state conditions for the intercooled gas turbine should be variable cycle control. The necessity of integration optimization design for gas turbine and intercooler is indicated and the modeling and analysis method developed in this paper should be beneficial to it

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

Case Report: Perivascular epithelioid tumors of the gastrointestinal tract

BackgroundPerivascular epithelioid cell tumor of the gastrointestinal tract (GI PEComa) is a rare mesenchymal neoplasm. GI PEComa is mostly observed in the colon and has a marked middle-aged female predominance. PEComa has no typical clinical or imaging manifestations or endoscopic characteristics. Therefore, the diagnosis of this disease mostly relies on pathological findings. HMB-45 is a sensitive immune marker of PEComa.Case presentationWe reported a case of a middle-aged female with sigmoid colon PEComa. To exclude carcinogenesis, the large basal polyp in the sigmoid colon was removed by endoscopic mucosal resection (EMR). Immunohistochemistry analysis results showed that this lesion expressed HMB-45, which is a characteristic melanin marker of PEComa. Finally, the lesion was diagnosed as sigmoid colon PEComa. At the time of submission of this report, surgical resection was the primary treatment for PEComa. Though the characteristics of tumor biology and clinical behavior in PEComa are not clear, the boundary is clear, and the tumor can be completely removed. However, close follow-up is required after the surgery because of the lesion’s undetermined benign and malignant nature.ConclusionThe present case study emphasizes the importance of pathological diagnosis. Therefore, upon finding gastrointestinal polyps with a mucosal ulcer under endoscopy, the GI PEComa diagnosis should be considered. It is necessary to detect the characteristic melanin markers of PEComa. Due to the rarity of these cases, challenges are faced in diagnosing and treating PEComa

A mouse line for inducible and reversible silencing of specific neurons

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements: We thank Dr. Joseph W. Lynch for sharing the IVMR plasmid, and Dr. Lisa M. Monteggia for sharing the AAV2-Cre plasmid. Rosa-CAG targeting vector was obtained from Addgenes. This work was supported by the Key State Research Program from Ministry of Science and Technology of China (2011CB510005, 2012CB966900, 2013CB835103), National Natural Science Foundation of China (81221001, 81200692, 81101026, 31100788, 31271182, 31030034, 91232724), Science and Technology Commission of Shanghai Municipality (12XD1404800), Shanghai Pujiang Program (12PJ1408800), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04) and Sino-UK Higher Education Research Partnership for PhD Studies.Peer reviewedPublisher PD

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development

He-Jie-Shen-Shi Decoction as an Adjuvant Therapy on Severe Coronavirus Disease 2019: A Retrospective Cohort and Potential Mechanistic Study

Combination therapy using Western and traditional Chinese medicines has shown notable effects on coronavirus disease 2019 (COVID-19). The He-Jie-Shen-Shi decoction (HJSS), composed of Bupleurum chinense DC., Scutellaria baicalensis Georgi, Pinellia ternata (Thunb.) Makino, Glycyrrhiza uralensis Fisch. ex DC., and nine other herbs, has been used to treat severe COVID-19 in clinical practice. The aim of this study was to compare the clinical efficacies of HJSS combination therapy and Western monotherapy against severe COVID-19 and to study the potential action mechanism of HJSS. From February 2020 to March 2020, 81 patients with severe COVID-19 in Wuhan Tongji Hospital were selected for retrospective cohort study. Network pharmacology was conducted to predict the possible mechanism of HJSS on COVID-19-related acute respiratory distress syndrome (ARDS). Targets of active components in HJSS were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases. The targets of COVID-19 and ARDS were obtained from GeneCards and Online Mendelian Inheritance in Man databases. The key targets of HJSS in COVID-19 and ARDS were obtained based on the protein–protein interaction network (PPI). Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) was conducted to predict the pathways related to the targets of HJSS in COVID-19 and ARDS. A “herb-ingredient-target-pathway” network was established using Cytoscape 3.2.7. Results showed that the duration of the negative conversion time of nucleic acid was shorter in patients who received HJSS combination therapy. HJSS combination therapy also relieved fever in patients with severe COVID-19. Network pharmacology analysis identified interleukin (IL) 6, tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), catalase (CAT), mitogen-activated protein kinase (MAPK) 1, tumor protein p53 (TP53), CC-chemokine ligand (CCL2), MAPK3, prostaglandin-endoperoxide synthase 2 (PTGS2), and IL1B as the key targets of HJSS in COVID-19-related ARDS. KEGG analysis suggested that HJSS improved COVID-19-related ARDS by regulating hypoxia-inducible factor (HIF)-1, NOD-like receptor, TNF, T cell receptor, sphingolipid, PI3K-Akt, toll-like receptor, VEGF, FoxO, and MAPK signaling pathways. In conclusion, HJSS can be used as an adjuvant therapy on severe COVID-19. The therapeutic mechanisms may be involved in inhibiting viral replication, inflammatory response, and oxidative stress and alleviating lung injury. Further studies are required to confirm its clinical efficacies and action mechanisms

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Tunneling nanotubes provide a new route for bovine viral diarrhea virus spreading

IntroductionBovine viral diarrhea virus (BVDV) is one of the major pathogens currently endangering the world's cattle industry. It poses serious difficulties in prevention and treatment because it can infect cattle of all ages and the specific mechanism of its cell-to-cell transmission has not yet been fully clarified. Tunneling nanotubes (TNTs) are F-actin-rich tubules that connect to the cytoplasm of nearby cells. They have been found to play an important role in the transmission of several viruses, but studies on BVDV in TNTs have not been reported.MethodsFirstly, the transwell assay was employed to investigate the transmission routes of BVDV and its capacity to propagate via intercellular junctional structures in the presence of neutralizing antibodies. Secondly, preliminary characterization of these junctional structures was conducted through pharmacological intervention experiments using the microtubule stabilizer paclitaxel, the microtubule disruptor nocodazole, the F-actin disruptors cyclosporine D and spongiosin A, and the gap junction blocker glycine. Subsequently, we validated the composition, spatial positioning, microscopic morphology, and generation characteristics of intercellular junctional structures following BVDV infection. Finally, iSTORM and live-cell fluorescence dynamic imaging techniques, we observed the transmission of BVDV viral particles through TNTs.ResultsTranswell assays demonstrated that BVDV can be transmitted via direct intercellular contact, a mode of transmission unaffected by neutralizing antibodies. Pharmacological studies revealed that only the F-actin disruptors spongin A and cell relaxin D inhibited the formation of this structure, preliminarily identifying it as a tunnel nanotube. Validation experiments confirmed that the composition, spatial orientation, microstructure, and formation direction of this connecting structure align with tunneling nanotube characteristics, further substantiating its identity as TNTs. iSTORM and live-cell fluorescence dynamic imaging revealed that BVDV particles can traverse TNTs to complete intercellular infection.DiscussionWe first report that BVDV can induce the formation of tunneling nanotubes and exploits this route to spread to uninfected cells. Our data highlight a previously unknown route of BVDV spreading, which could have significant implications for celler transmission and immune evasion