Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in ...China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest
National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV
(the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
Abstract
The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we ...implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS.
Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related ...malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.
Genome-wide association study (GWAS) entails examining a large number of single nucleotide polymorphisms (SNPs) in a limited sample with hundreds of individuals, implying a variable selection problem ...in the high dimensional dataset. Although many single-locus GWAS approaches under polygenic background and population structure controls have been widely used, some significant loci fail to be detected. In this study, we used an iterative modified-sure independence screening (ISIS) approach in reducing the number of SNPs to a moderate size. Expectation-Maximization (EM)-Bayesian least absolute shrinkage and selection operator (BLASSO) was used to estimate all the selected SNP effects for true quantitative trait nucleotide (QTN) detection. This method is referred to as ISIS EM-BLASSO algorithm. Monte Carlo simulation studies validated the new method, which has the highest empirical power in QTN detection and the highest accuracy in QTN effect estimation, and it is the fastest, as compared with efficient mixed-model association (EMMA), smoothly clipped absolute deviation (SCAD), fixed and random model circulating probability unification (FarmCPU), and multi-locus random-SNP-effect mixed linear model (mrMLM). To further demonstrate the new method, six flowering time traits in Arabidopsis thaliana were re-analyzed by four methods (New method, EMMA, FarmCPU, and mrMLM). As a result, the new method identified most previously reported genes. Therefore, the new method is a good alternative for multi-locus GWAS.
Majorana bound states often occur at the end of a 1D topological superconductor. Validated by a new bulk invariant and an intuitive edge argument, we show the emergence of one Majorana Kramers pair ...at each corner of a square-shaped 2D topological insulator proximitized by an s_{±}-wave (e.g., Fe-based) superconductor. We obtain a phase diagram that addresses the relaxation of crystal symmetry and edge orientation. We propose two experimental realizations in candidate materials. Our scheme offers a higher-order and higher-temperature route for exploring non-Abelian quasiparticles.
Separations and analyses of chiral compounds are important in many fields, including pharmaceutical production, preparation of chemical intermediates, and biochemistry. High‐performance liquid ...chromatography using a chiral stationary phase is regarded as one of the most valuable methods for enantiomeric separation and analysis because it is highly efficient, is broadly applicable, and has powerful separation capability. The focus for development of this method is the identification of novel chiral stationary phases with superior recognition performance and good stability. The present article reviews recent progress in the development of new chiral stationary phases for high‐performance liquid chromatography between January 2018 and June 2021. These newly reported chiral stationary phases are divided into three categories: small organic molecule‐based (cyclodextrin and its derivatives, macrocyclic antibiotics, cinchona alkaloids, and other low molecular weight chiral molecules), macromolecule‐based (cellulose and amylose derivatives, chitin and chitosan derivatives, and synthetic helical polymers) and chiral porous material‐based (chiral metal‐organic frameworks, chiral covalent organic frameworks, and chiral inorganic mesoporous silicas). Each type of chiral stationary phase is discussed in detail.
Today East Asia harbors many "relict" plant species whose ranges were much larger during the Paleogene-Neogene and earlier. The ecological and climatic conditions suitable for these relict species ...have not been identified. Here, we map the abundance and distribution patterns of relict species, showing high abundance in the humid subtropical/warm-temperate forest regions. We further use Ecological Niche Modeling to show that these patterns align with maps of climate refugia, and we predict species' chances of persistence given the future climatic changes expected for East Asia. By 2070, potentially suitable areas with high richness of relict species will decrease, although the areas as a whole will probably expand. We identify areas in southwestern China and northern Vietnam as long-term climatically stable refugia likely to preserve ancient lineages, highlighting areas that could be prioritized for conservation of such species.
Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild ...apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m
yr
, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m
yr
, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m
yr
, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m
yr
, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments.
N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4).
Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations.
Porous materials with well‐defined pore structures have received considerable attention in the past decades due to their unique structures and wide applications. Most porous materials such as ...zeolites, metal‐organic frameworks, covalent organic frameworks, and porous organic polymers are extended to infinite frameworks or networks by robust covalent or coordination bonds. Porous molecular cages composed of discrete molecules with permanent cavities are an emerging class of porous material and the discrete molecules assemble into solids by weak intermolecular interaction. In comparison to porous extended solids such as metal‐organic frameworks and covalent organic frameworks, porous molecular cage solids are generally soluble in organic solvents thus allowing solution processing, making them more convenient to apply in many fields. This review mainly focuses on the recent advances of application of porous molecular cages (porous organic cages and metal‐organic cages) for enantioselective recognition and separation from 2010 to present, including gas chromatography, capillary electrochromatography, chiral fluorescent recognition, chiral potentiometric sensing, and enantioselective adsorption. Furthermore, the two important family members of porous molecular cages, porous organic cages and metal‐organic cages, are also discussed.
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