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Increasing evidence shows the African lineage Zika virus (ZIKV) displays a more severe neurovirulence compared to the Asian ZIKV. However, viral determinants and the underlying mechanisms of enhanced virulence phenotype remain largely unknown. Herein, we identify a panel of amino acid substitutions that are unique to the African lineage of ZIKVs compared to the Asian lineage by phylogenetic analysis and sequence alignment. We then utilize reverse genetic technology to generate recombinant ZIKVs incorporating these lineage-specific substitutions based on an infectious cDNA clone of Asian ZIKV. Through in vitro characterization, we discover a mutant virus with a lysine to arginine substitution at position 101 of capsid (C) protein (termed K101R) displays a larger plaque phenotype, and replicates more efficiently in various cell lines. Moreover, K101R replicates more efficiently in mouse brains and induces stronger inflammatory responses than the wild type (WT) virus in neonatal mice. Finally, a combined analysis reveals the K101R substitution promotes the production of mature C protein without affecting its binding to viral RNA. Our study identifies the role of K101R substitution in the C protein in contributing to the enhanced virulent phenotype of the African lineage ZIKV, which expands our understanding of the complexity of ZIKV proteins. The neurovirulence determinants of Zika virus remain not fully established. Song et al identified a single K101R substitution in the capsid protein that contributes to the lineage-specific virulence phenotypes.

Parathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer - it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention.

The characteristics including surface morphology, phase constitution, thickness and the corrosion resistance of the porously anodic films prepared in the sulfuric electrolyte with different additives at 35°C were investigated by SEM, EDS, XRD and electrochemical polarization method in this paper. The additives are organic acids, polyhydric alcohols and rare earth (REE) salts. A porous anodic film with about 20 nm holes in diameter can be obtained by additives into the sulfuric electrolyte. The main chemical compositions of the anodic films are Al, O elements, and a small amount of S. The film after boiling water sealing is composed of boehmite (Al2O3·H2O) and alumina (Al2O3) phases. The compactness and the thickness of the anodic films can be improved by the coupling effect of the additives, which increases the corrosion resistance of the film. The effect of additives on morphologies and corrosion resistance is discussed.

The characterization in microstructure, morphology and oxidation behavior of three iron-based coatings by Supersonic Arc Spraying (HVAS), were investigated by XRD, FESEM, EDS and thermal exposure in furnace in this paper. It is indicated that the three coatings are typical layer and compact structure. The coatings are composed of Fe (s.s) phase and kinds of ferric oxides, chrome carbides and/ or intermetallic phase distributing along the interface of lamellar layers. More Cr and Ti, Al elements can alternate the diameter and morphologies of the holes, resulting from the formation of oxides, carbides and intermetallic phase. The results indicate that SXTiAlC coating shows the most excellent oxidation resistance with 2.70 mg·cm-2 in mass gain, while that are 88.08 mg·cm-2 and 16.64 mg·cm-2 after 100 h thermal exposure at 800°C for LX88A and SXHCrA coatings, respectively. The oxidation behavior is discussed.

The characteristics in microstructure, surface morphology, chemical composition, hardness and wear resistance of the three protective iron-based compound coatings prepared by Supersonic Arc Spraying (HVAS), were investigated by X-ray diffraction (XRD), Field emission scanning electron microscope (FESEM), Energy disperse spectroscopy (EDS) and Rockwell apparatus in this paper. It is indicated that the three coatings are typical layer and compact structures. The coatings are composed of Fe (s.s) phase and various kinds of ferric oxides, chrome carbides and/or intermetallic phase distributing along the interface of lamellar layers. More Cr and Ti, Al elements in the cored wires can degrease the diameter and alternate the morphologies of the holes in the coating, resulting from the formation of oxides, carbides and intermetallic phase during depositing the coating. The results indicate the SXTiAlC coating shows the most excellent wear performance among the three coatings. The wear behavior and mechanism are discussed.

The surface morphologies, chemical composition, phase composition, compactness, thickness and the corrosion resistance of porous anodic films prepared in the sulfuric electrolyte with different additives at 35°C were investigated by XRD, FESEM, EDS, drop method in this paper. The additives are including organic acids, polyhydric alcohols and rare earth (REE) salts. It is indicated that a porously anodic film with about 20 nm holes in diameter can be obtained by additives into the sulfuric electrolyte. The main chemical compositions of the anodic films are Al, O elements, and a small amount of S. The film after boiling water sealing is composed of boehmite phase (Al2O3·H2O) and alumina (Al2O3). The corrosion resistance of the anodic film can be improved by the coupling effect of the additives. The mechanism is discussed.

The characterization in microstructure, morphology and oxidation behavior of three iron-based coatings by Supersonic Arc Spraying (HVAS), were investigated by XRD, FESEM, EDS and thermal exposure in furnace in this paper. It is indicated that the three coatings are typical layer and compact structure. The coatings are composed of Fe (s.s) phase and kinds of ferric oxides, chrome carbides and/ or intermetallic phase distributing along the interface of lamellar layers. More Cr and Ti, Al elements can alternate the diameter and morphologies of the holes, resulting from the formation of oxides, carbides and intermetallic phase. The results indicate that SXTiAlC coating shows the most excellent oxidation resistance with 2.70 mg cm-2 in mass gain, while that are 88.08 mg cm-2 and 16.64 mg cm-2 after 100 h thermal exposure at 800 degree C for LX88A and SXHCrA coatings, respectively. The oxidation behavior is discussed.

[Objective]In order to carriy on effective medication and immune prevention and control,pathogen and etiology of a Rana spinosa David disease in a Rana spinosa David breeding company in Zhejiang was researched from 2009 to 2010. [Methods]Conventional bacteria separation and purification technology was used to purify pathogenic bacteria,regression infection and toxicity test was used to determine its virulence,physiological and biochemical and molecular biology identification was carried out to the the pathogen,k- b paper method was adopted for the susceptibility test,normal paraffin wax flaking technology was used for pathology observations,finally,the inactivation conditions of pathogenic bacteria was explored. [Results]The pathogenic bacteria separated from sick Rana spinosa David body had Median Lethal Concentration（ LC 50） of 5.62 ×105 cfu / ml; the strain was identified as Aeromonas hydrophila by ATB bacteria identification instrument and 16 s rRNA sequence analysis（ GenBank login number： HQ322682）; histopathology observation results showed that the disease had main symptoms of the liver and kidney damage,inflammatory cells increase. Susceptibility test showed that the strain was highly sensitive to gentamicin,norfloxacin,florfenicol,enrofloxacin etc. [Conclusions]1% formaldehyde could well inactivate the pathogenic bacteria at 60 ℃ for 24 h,which would provide technical reference for whole bacteria inactivated vaccine preparation.

Muscle genetic defects can lead to impaired movement, respiratory failure, and other severe symptoms. The development of curative therapies is challenging due to the need for the delivery of gene-editing tools into skeletal muscle cells throughout the body. Here, we use muscular fusogens (Myomaker and Myomerger) to engineer muscle-specific virus-like particles (MuVLPs) for the systemic delivery of gene-editing tools. We demonstrate that MuVLPs can be loaded with diverse payloads, including EGFP, Cre and Cas9/sgRNA ribonucleoproteins (Cas9 RNPs), and can be delivered into skeletal muscle cells via targeted membrane fusion. Systemic administration of MuVLPs carrying Cas9 RNPs enables skeletal muscle-specific gene editing, which excised the exon containing a premature terminator codon mutation in a mouse model for Duchenne muscular dystrophy (DMD). This treatment restores dystrophin expression in various skeletal muscle tissues, including the diaphragm, quadriceps, tibialis anterior, gastrocnemius, and triceps. As a result, the treated mice exhibit a significantly increased capacity for exercise and endurance. This study established a platform for precise gene editing in skeletal muscle tissues. Genetic muscle diseases are difficult to treat due to challenges in delivering gene editors to muscles throughout the body. Here, authors engineer muscle-specific virus-like particles that fuse with skeletal muscle cells to deliver CRISPR tools and restore dystrophin in a DMD model.

Seed size and shape traits are closely related to seed yield and appearance quality in soybean (Glycine max L.). Previous studies were mainly derived from bi-parental segregating populations and relatively little is known about the results in soybean cultivars. In this study, 257 soybean cultivars obtained by stratified random sampling from six geographic ecotypes in China were used to carry out association mapping for these traits using information from 135 simple sequence repeat markers and an epistatic association mapping approach implemented using an empirical Bayes algorithm. In this analysis, seed size was measured by seed length (SL), width (SW) and thickness (ST), and seed shape was evaluated by seed length-to-width (SLW), length-to-thickness (SLT) and width-to-thickness (SWT) ratios, in 2008–2010. A total of 59 main-effect quantitative trait loci (QTL) and 31 QTL-by-environment interactions were identified. Among them, 25 QTL were associated simultaneously with at least two traits; 80 QTL (90 %) could be confirmed by enriched compression mixed linear model analysis; and the size for a large number of detected QTL was minor, except for qSL-5, qSW-7e, qST-5-2 and qSLW-2. According to the estimates for the allelic effects of the detected QTL, elite alleles could be mined: for example, the 307-bp allele of QTL linked to satt453 was the best for seed length. These elite alleles could be used to design parental combinations; e.g., the cross of Zhenghezhibanzi and Nannongdahuangdou might improve seed length, and the combination of cultivars Lindou10, Deqingxiangzhudou, Ninghaixiazhidou, Zhenghezhibanzi, 0803, Shangqiu7605 and 0831 might pyramid 42 elite alleles.