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Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus (DENV). DENV causes a febrile illness, severe forms including hemorrhagic fevers and shock with fatalities in humans. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 strains from Guangdong, China, have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo. A total of 22 patients tested to be DENV-2 positive and were enrolled in this study, 22 complete genomes were obtained by virus isolation and high-throughput sequencing. Phylogenetic and single amino polymorphism (SAP) analysis indicated that two major subgenotypes (A and C) of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018. The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains, including endemic genotype and imported genotype. It alerted the risk of cross-border transmission of DENV. A significant difference in replication rate was observed in C6/36 between different DENV-2 strains, although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles. DENV-2 subgenotypes (A and C) replicated efficiently in IFNAR−/− C57BL/6 mice, and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group. DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo, indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major public health threat worldwide. Insight into protective and pathogenic aspects of SARS-CoV-2 immune responses is critical to work out effective therapeutics and develop vaccines for controlling the disease. Here, we review the present literature describing the innate and adaptive immune responses including innate immune cells, cytokine responses, antibody responses and T cell responses against SARS-CoV-2 in human infection, as well as in AEC2-humanized mouse infection. We also summarize the now known and unknown about the role of the SARS-CoV-2 immune responses. By better understanding the mechanisms that drive the immune responses, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat., Graphical Abstract Image, graphical abstract

Antigen receptor assembly in lymphocytes involves stringently-regulated coordination of specific DNA rearrangement events across several large chromosomal domains. Previous studies indicate that transcription factors such as paired box 5 (PAX5), Yin Yang 1 (YY1), and CCCTC-binding factor (CTCF) play a role in regulating the accessibility of the antigen receptor loci to the V(D)J recombinase, which is required for these rearrangements. To gain clues about the role of CTCF binding at the murine immunoglobulin heavy chain (IgH) locus, we utilized a computational approach that identified 144 putative CTCF-binding sites within this locus. We found that these CTCF sites share a consensus motif distinct from other CTCF sites in the mouse genome. Additionally, we could divide these CTCF sites into three categories: intergenic sites remote from any coding element, upstream sites present within 8 kb of the VH-leader exon, and recombination signal sequence (RSS)-associated sites characteristically located at a fixed distance (∼18 bp) downstream of the RSS. We noted that the intergenic and upstream sites are located in the distal portion of the VH locus, whereas the RSS-associated sites are located in the DH-proximal region. Computational analysis indicated that the prevalence of CTCF-binding sites at the IgH locus is evolutionarily conserved. In all species analyzed, these sites exhibit a striking strand-orientation bias, with >98% of the murine sites being present in one orientation with respect to VH gene transcription. Electrophoretic mobility shift and enhancer-blocking assays and ChIP–chip analysis confirmed CTCF binding to these sites both in vitro and in vivo.

Resveratrol is a natural antioxidant in a wide variety of plant species, developing an effective strategy to further improve its antioxidative activity has attracted enormous research attention in recent years. In this work, tetra-(3,5-dihydroxy)styryl-calix[4]arene (TSC, a calix[4]arene-like tetramer of resveratrol) has been theoretically studied at the DFT-BP86/6-311+G(d,p) level of theory. The results demonstrates that TSC has highly symmetrical molecular geometry with four equivalent resveratrol units, the 4′-O H and 4′-C O bonds were elongated and distinct deviation from planarity was observed in four resveratrol units in TSC. More interestingly, TSC has remarkably lower 4′-OH BDE, IP, and PA of 4′-phenolate than those of resveratrol, indicating that TSC exhibits much more excellent antioxidative activities than resveratrol. Spin density in 4′-phenoxyl radical and cation radical are delocalized over whole molecular skeleton of TSC, thus leading to more stable radical species than that of resveratrol. The topologies analysis of unpaired electron occupying orbitals reveals that calix[4]arene skeleton plays very important role in delocalization of unpaired electron. Molecular simplification studies proved that the synergistic effect of calix[4]arene skeleton, the A benzene ring and C C double bonds on the upper rim were responsible for the higher activity of TSC, and calix[4]arene skeleton amongst played the most important role.

BACKGROUND: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV. METHODS: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses. FINDINGS: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54). INTERPRETATION: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused. FUNDING: The National Science and Technology Major Project, National Institutes of Health.

Summary COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines., An adenoviral transduction-based mouse model that can be infected with SARS-CoV-2 provides a tool to understand host factors involved in viral infection and clearance as well as potential therapeutic modalities.

Background: The gut microbiome represents a niche for biomarkers discovery to risk-stratify MAFLD patients. However, each population may have unique microbiome signatures and studies are needed in Latin America where MAFLD prevalence and severity are high. Aims: To identify gut metatranscriptome and metabolome signatures associated with MAFLD and steatohepatitis (SH) in Argentina. Methods: Stool samples, diet, demographic and clinical data were obtained from 33 biopsy-proven patients (12 simple steatosis -SS- and 21 SH) and 19 healthy volunteers (HV). PNPLA3 rs738409 SNP was genotyped. HPLC, flow injection analysis with MS/MS in tandem and MetaboAnalyst-v4.0 were used for metabolomics. RNA-seq was performed in NovaSeq6000®. bioBakery-v1.8 and Maaslin2-v1.2.0 were used for data analysis. Results: BMI was higher in MAFLD patients, particularly in SH (q=4.49e-06). After adjusting for BMI, 89 and 53 gene family clusters were differentially expressed between HV and MAFLD and between SS and SH, respectively (q

Catalytic dehydration and dehydrogenation reactions of ethanol have been investigated systematically using the ab initio quantum chemistry methods The catalysts include water, hydrogen peroxide, formic acid, phosphoric acid, hydrogen fluoride, ammonia, and ethanol itself. Moreover, a few clusters of water and ethanol were considered to simulate the catalytic mechanisms in supercritical water and supercritical ethanol. The barriers for both dehydration and dehydrogenation can be reduced significantly in the presence of the catalysts. It is revealed that the selectivity of the catalytic dehydration and dehydrogenation depends on the acidity and basicity of the catalysts and the sizes of the clusters. The acidic catalyst prefers dehydration while the basic catalysts tend to promote dehydrogenation more effectively. The calculated water-dimer catalysis mechanism supports the experimental results of the selective oxidation of ethanol in the supercritical water. It is suggested that the solvent- and catalyst-free self-oxidation of the supercritical ethanol could be an important mechanism for the selective dehydrogenation of ethanol on the theoretical point of view.

Highlights • We report one novel complete genome (CRCoV BJ232) of CRCoV from China. • CRCoV BJ232 form a separate clade from other Betacoronavirus 1. • CRCoV-K37 was derived from genetic recombination between CRCoV-BJ232 and BCoV. • We confirmed the prevalence of CRCoV-BJ232 lineage around the world for a long time., Although canine respiratory coronavirus (CRCoV) is an important respiratory pathogen that is prevalent in many countries, only one complete genome sequence of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses and recombination have rarely been conducted, as small numbers of samples and limited genomic characterization have previously prevented further analyses. Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based on complete genome of all available coronaviruses consistently show that CRCoV BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV, forming a separate clade that split off early from other Betacoronavirus 1. Based on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S) gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV-B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage around the world for a long time. Recombinant events among Betacoronavirus 1 may have implications for CRCoV transmissibility. All these findings provide further information regarding the origin of CRCoV.

The mechanism of the reaction of Methylidyne Radical (CH) with acetaldehyde (CH 3 CHO) has been investigated using CBS-QB3//B3LYP/aug-cc-pVTZ method. The initial CH + CH 3 CHO reaction is a barrierless process, forming a linear intermediate, CH 3 CHOCH, which can be converted into several products. The microscopic mechanism recommended by the present study not only identifies the products observed by previous experimental studies but also explains the isotopic effects (CH/CCD) observed experimentally. In view of the calculated energies, C 2 H 5 + CO is the most exothermic product pair, additionally, the energy barrier of this product channel is the lowest. Concerning the hydrogen elimination channel, acrolein (CH 2 CHCHO) and methylketene (CH 3 CHCO) are preferable co-products. Furthermore, a new product channel, C 2 H 3 + CH 2 O, has been discovered.

The essential functions of polycomb repressive complex 1 (PRC1) in development and gene silencing are thought to involve long non-coding RNAs (lncRNAs), but few specific lncRNAs that guide PRC1 activity are known. We screened for lncRNAs, which co-precipitate with PRC1 from chromatin and found candidates that impact polycomb group protein (PcG)-regulated gene expression in vivo. A novel lncRNA from this screen, CAT7, regulates expression and polycomb group binding at the MNX1 locus during early neuronal differentiation. CAT7 contains a unique tandem repeat domain that shares high sequence similarity to a non-syntenic zebrafish analog, cat7l. Defects caused by interference of cat7l RNA during zebrafish embryogenesis were rescued by human CAT7 RNA, enhanced by interference of a PRC1 component, and suppressed by interference of a known PRC1 target gene, demonstrating cat7l genetically interacts with a PRC1. We propose a model whereby PRC1 acts in concert with specific lncRNAs and that CAT7/cat7l represents convergent lncRNAs that independently evolved to tune PRC1 repression at individual loci.

Low-intensity ultrasound therapy has been found to be a potential tool in the management of malignant tumors in recent years. However, the molecular mechanism underlying low-intensity ultrasound-induced apoptosis is still not clear. In this study, we investigated the effects of low-intensity ultrasound-induced apoptosis in HEp-2 cells. We found that low-intensity ultrasound significantly induced apoptosis, and the expression level of caveolin-1 (Cav-1) was dramatically increased after ultrasound treatment of HEp-2 cells. After inhibiting the expression level of Cav-1 using siRNA transfection, we found that the cellular apoptosis induced by low-intensity ultrasound was significantly suppressed. In addition, inhibition of Cav-1 expression promoted phosphorylation of signal transducer and activator of transcription 3 (STAT3), suggesting that the STAT3 signaling pathway was involved in low-intensity ultrasound-induced apoptosis via Cav-1 regulation. Our results indicate that Cav-1/STAT3 signaling pathway may mediate low-intensity ultrasound-induced apoptosis, and this technology could potentially be used clinically for the treatment of cancers.

Drought is one of the major climatic disasters intimidating winter wheat production in the Huang-Huai-Hai (3H) Plain of China. The yield damage caused by drought tends to increase in the future, indicated by a pronounced uprising of drought events under RCP 8.5 scenario in terms of its affecting magnitude and area. This paper presents a modeling approach by using crop model DSSAT and hydrological indices to assess the vulnerability of winter wheat to future potential drought, based on an integrated assessment of exposure, sensitivity and adaptive capacity. Our results demonstrate that Beijing, Tianjin, Hebei and Shandong are more exposed and sensitive to potential drought than other regions in 3H. Traditional irrigation has the greater benefits in northern 3H Plain than southern regions, but is still insufficient to impede the yield loss due to potential drought. Under RCP 8.5 emission scenario and the period of 2010–2050, the worst drought effect is projected to occur around 2030. More than half of 3H plain are subject to high drought vulnerability. With increasing drought risks, we suggest immediate and appropriate adaptation actions to be taken before 2030s, especially in Shandong and Hebei, the most vulnerable provinces of 3H plain.

Nitrogen (N) is one of the macronutrients required for plant growth, and reasonable application of N fertilizers can increase crop yields and improve their quality. However, excessive application of N fertilizers will decrease N use efficiency and also lead to increases in N2O emissions from agricultural soils and many other environmental issues. Research on the effects of different N fertilizer management practices on wheat yields and N2O emissions will assist the selection of effective N management measures which enable achieving high wheat yields while reducing N2O emissions. To investigate the effects of different N management practices on wheat yields and soil N2O emissions, we conducted field trials with 5 treatments of no N fertilizer (CK), farmers common N rate (AN), optimal N rate (ON), 20% reduction in optimal rate+dicyandiamide (ON80%+DCD), 20% reduction in optimal rate+nano-carbon (ON80%+NC). The static closed chamber gas chromatography method was used to monitor N2O emissions during the wheat growing season. The results showed that there were obvious seasonal characteristics of N2O emissions under each treatment and N2O emissions were mainly concentrated in the sowing-greening stage, accounting for 54.6–68.2% of the overall emissions. Compared with AN, N2O emissions were decreased by 23.1, 45.4 and 33.7%, respectively, under ON, ON80%+DCD and ON80%+NC, and emission factors were declined by 22.2, 66.7 and 33.3%, respectively. Wheat yield was increased significantly under ON80%+DCD and ON80%+NC by 12.3 and 11.9%, respectively, relative to AN while there was no significant change in yield in the ON treatment. Compared with ON, overall N2O emissions were decreased by 29.1 and 13.9% while wheat yields improved by 18.3 and 17.9% under ON80%+DCD and ON80%+NC, respectively. We therefore recommend that ON80%+DCD and ON80%+NC be referred as effective N management practices increasing yields while mitigating emissions.

In this paper, the global stability has been investigated for a novel class of competitive neural networks with mixed time delays and discontinuous activations. Without presuming the boundedness of activation functions, we draw two set of sufficient conditions ensuring the existence, uniqueness of the equilibrium, global exponential asymptotic stability of the solution and the associated output of the solution converging to the output equilibrium point in measure, by linear matrix inequality, M-matrix, Leray-Schauder alternative theorem in multivalued analysis, general Lyapunov method, topological degree theory of set-valued map. Meanwhile, we present a result on the global convergence in finite time of given neural networks. The results in the literature are generalized and significantly improved. Finally, one example and simulations are presented to demonstrate the effectiveness of the theoretical results.

AIM To evaluate the role of MRI in preoperative assessments of patients with a persistent cloaca and compare magnetic resonance imaging (MRI) versus fluoroscopy contrast study in the accuracy of common canal measurement and classification prediction. MATERIALS AND METHODS Thirty-one patients with a persistent cloaca were diagnosed and treated at Guangzhou Women and Children's Medical Center between March 2011 and December 2017. The length of the common canal was measured using MRI and fluoroscopy contrast study. Classification results based on measurements were compared with cystoscopy and intraoperative findings. The accuracy in predicting the classification by measuring the common canal length was compared. RESULT Among 31 patients, 24 had MRI, 24 underwent fluoroscopy contrast study, and 25 underwent cystoscopy. In 20 patients, MRI-based categorisations were in accordance with cystoscopy or surgery findings, whereas in four patients there was discordance. In 17 patients, categorisations based on fluoroscopy contrast study were in accordance with cystoscopy or surgery findings, and in seven patients there was discordance; the difference was not statistically significant (p>0.05). CONCLUSION MRI may accurately demonstrate genitourinary anomalies and the length of the common canal in patients with persistent cloaca. Categorisation based on MRI measurements of the common canal was accordant with the results from cystoscopy and findings from surgery. The use of this method may help surgeons to develop appropriate reconstruction plans before sending their patients to the operating room.

In this paper, we investigate the dynamical behaviors of a novel class of Cohen-Grossberg neural networks with not only mixed time delays, i.e., time varying delays and distributed delays, but also discontinuous activations, which may be unbounded or nonmonotonic. Some sufficient conditions are derived to ensure the existence, uniqueness of the equilibrium, global exponential asymptotic stability of the solution and the associated output of the solution converging to the output equilibrium point in measure by using the Leray-Schauder alternative theorem in multivalued analysis, matrix theory and generalized Lyapunov-like approach. Some recent results in the literature are generalized and significantly improved. One example is provided to demonstrate the effectiveness of the theoretical results.