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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.

Aim： Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitMty in esophageal cancers. Methods： A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay （ATP-TCA）. Results： Thirty eight specimens produced evaluable results （90.5%）. The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity： cisplatin＋paclitaxel was sensitive in 16 of 38 （42.1%） of samples, while nedaplatin＋paclitaxel was more effective, which was sensitive in 20 of 38 cases （52.6%）. Conclusion： There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients.

Cable-type welding wire（CWW）CO2 welding is an innovative process arc welding with high quality,high efficiency and energy saving,in which CWW is used as consumable electrode.The CWW is composed of seven wires with a diameter of 1.2mm.One is in the center,while others uniformly distribute around it.The diameter of twisted wire is up to 3.6mm,which can increase the deposition rate significantly.With continual wire-feeding and melting of CWW,the formed rotating arc improved welding quality obviously.The arc behavior and droplet transfer were observed by the electrical signal waveforms and corresponding synchronous images,based on the high speed digital camera and electrical signal system.The results showed that the shape of welding arc changed from bell arc to beam arc with the increase of welding parameter.The droplet transfer mode changed from repelled transfer,globular transfer to projected transfer in turn.Droplet transfer frequency increased from 18.17 Hz to 119.05 Hz,while the droplet diameter decreased from 1.5times to 0.3times of the CWW diameter.

Aim： The present study aimed to elucidate the role of T-subtype calcium channels （Cav3.1, Cav3.2, and Cav3.3） in the pathogenesis of neuropathic pain at spinal level. Methods： The chronic compression of the dorsal root ganglion （CCD） rat model was adopted. The antisense oligonucleotide of Cav3.1, Cav3.2, and Cav3.3 or normal saline （NS） were intrathecally administered twice per day from the first day to the fourth day after operation. Paw mechanical withdrawal threshold and paw thermal withdrawal latency were measured to evaluate the tactile allodynia and thermal hyperalgesia, respectively. Results： CCD rats developed reliable tactile allodynia and thermal hyperalgesia after operation. Intrathecal administration of antisense oligonucleotide of Cav3.2 and Cav3.3 significantly relieved tactile allodynia and thermal hyperalgesia in CCD rats, but not Cav3.1. Conclusion： Cav3.2 and Cav3.3 subtype calcium channels in the spinal cord may play an important role in the pathogenesis of neuropathic pain, which may contribute to the management of the neuropathic pain.