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In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.

At present, a large number of curcumin derivatives had been produced and identified aiming to replace the curcumin in view of its low bioavailability and stability. Here, a novel curcumin derivative ZYX02-Na was first used to reduce the cell viability of human non-small cell lung cells A549, which was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and Western blot analysis showed that ZYX02-Na could lead to cell cycle arrest in G0/G1 phase, which demonstrated that ZYX02-Na inhibited the proliferation of A549 cells. Furthermore, the AMPK/mTOR/4E-BP1 signaling pathway was activated in ZYX02-Na-treated A549 cells. Besides, wounding healing and transwell experiments showed that ZYX02-Na could also inhibited the migration ability of A549 cells. Moreover, we also found that ZYX02-Na could induce autophagy of A549 cells by acridine orange staining, GFP-LC3 subcellular localization observation and Western blotting analysis, respectively. In short, our current studies indicated that ZYX02-Na possessed the antiproliferation effect and autophagy induction on A549 cells, while in vivo anticancer study of ZYX02-Na needs to be done in future., (© 2020 Wiley Periodicals LLC.)

Brassica napus is an important oilseed crop in the world, and the mechanism of seed oil biosynthesis in B. napus remains unclear. In order to study the mechanism of oil biosynthesis and generate germplasms for breeding, an ethyl methanesulfonate (EMS) mutant population with ~100 000 M2 lines was generated using Zhongshuang 11 as the parent line. The EMS-induced genome-wide mutations in M2-M4 plants were assessed. The average number of mutations including single nucleotide polymorphisms and insertion/deletion in M2-M4 was 21 177, 28 675 and 17 915, respectively. The effects of the mutations on gene function were predicted in M2-M4 mutants, respectively. We screened the seeds from 98 113 M2 lines, and 9415 seed oil content and fatty acid mutants were identified. We further confirmed 686 mutants with altered seed oil content and fatty acid in advanced generation (M4 seeds). Five representative M4 mutants with increased oleic acid were re-sequenced, and the potential causal variations in FAD2 and ROD1 genes were identified. This study generated and screened a large scale of B. napus EMS mutant population, and the identified mutants could provide useful genetic resources for the study of oil biosynthesis and genetic improvement of seed oil content and fatty acid composition of B. napus in the future., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue with an extended half-life of approximately 1 week has being come into clinic trial to treat parkingson's disease but little is known about its effect to prevent against Alzheimer's disease (AD). The goal of the present study was to explore the potential mechanisms of semaglutide to protect against AD., Methods: We treated SH-SY5Y cell line with Aβ 25-35 as an AD model. Further, SH-SY5Y cells damaged by Aβ 25-35 were treated by semaglutide. Autophagy-related proteins and apoptosis-related proteins were measured to explore molecular mechanisms for semaglutide to protect against Aβ 25-35 ., Results: Semaglutide enhanced autophagy by increasing the expression of LC3II, Atg7, Beclin-1 and P62 which were inhibited by Aβ 25-35 . Further we showed that semaglutide inhibited apoptosis by inhibiting the expression of Bax induced by Aβ 25-35 and increasing the expression of Bcl2 inhibited by Aβ 25-35 ., Conclusion: Our results provide a clue for the hypothesis that autophagy enhancement and apoptosis inhibition may be involved in the effect of semaglutide to protect against Aβ 25-35 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease of swine characterized by respiratory disorders in growing and finishing pigs and reproductive failure in pregnant sows. PRRSV has been recognized as one of the most economically significant pathogens affecting the global pig industry., Areas Covered: Currently, commercially available vaccines, including traditional killed virus (KV) vaccines and modified live virus (MLV) vaccines, are the cardinal approaches to prevent and control porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the protective efficacy of these vaccines is not satisfactory, resulting in the continuous evolution and recurrent appearance of the virus as well as the emergence of new variants. A safe and effective vaccine against PRRSV is in dire need. Here, we review the research progress in recent years in the development and use of PRRSV as a viral vector to express foreign genes, and their potential application in gene delivery and vaccine development., Expert Opinion: The potential of using PRRSV-based vectors to express multiple antigens would be particularly instrumental for the development of a new generation of multivalent vaccines against PRRSV and other porcine viruses.

Objective: Flow dephasing artifacts within intracranial internal carotid artery (ICA) have been problematic for 3D time-of-flight magnetic resonance angiography (3D-TOF-MRA). This study aimed to evaluate pointwise encoding time reduction with radial acquisition subtraction-based MR angiography (PETRA-MRA) for decreasing flow dephasing artifacts compared to 3D-TOF-MRA in intracranial segments of ICA at 3 T., Methods: Sixty healthy participants and seven patients with intracranial ICA aneurysms were enrolled to undergo 3D-TOF-MRA and PETRA-MRA. Two radiologists each evaluated the image quality of healthy participants using a 4-point scale (1: the best and 4: the worst). Quantitative analysis of the extent of homogeneity in signal intensity within the ICA and intracranial aneurysms was conducted using a parameter d: the higher the d value, the greater the signal homogeneity. Wilcoxon signed rank test, Chi-square test and the weighted kappa (κ) statistic were used for statistical analyses., Results: The image quality of PETRA-MRA with an overall score of 1.35 ± 0.53 was significantly better than that obtained with 3D-TOF-MRA, with an overall score of 3.50 ± 0.62 (Z = -9.56, p < 0.001). The parameter d of PETRA-MRA was higher than that of 3D-TOF-MRA for both 60 healthy participants (0.97 ± 0.05, 0.87 ± 0.11; z = -13.21, p < 0.001) and 7 patients with intracranial aneurysms (0.81 ± 0.18, 0.74 ± 0.16; z = -2.37, p = 0.018)., Conclusion: Compared with conventional 3D-TOF-MRA, PETRA-MRA remarkably improved the image quality with reduced flow dephasing artifacts in segments of intracranial ICA., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case fatality rate (CFR). Alcohol consumption which impairs host immunity and contributes to tissue damage in a variety of organs may be a predisposing factor of fatal outcome in SFTS. We aimed to determine the role of alcohol consumption on the fatal outcome of SFTS. Patients with laboratory-diagnosed SFTS who were admitted to the Jinan Infectious Disease Hospital, Jinan, China, between January 2011 and November 2018 were evaluated. Demographic, clinical, and laboratory data were recorded. Alcohol consumption was evaluated. The association between a fatal outcome and each demographic, clinical, and laboratory variable with alcohol consumption was assessed. A total of 694 patients with SFTS were identified during the study period. The overall CFR was 20.9 % (95 % CI: 17.9 %-23.9 %). The CFR in non/light drinkers (0-98 g/week) and moderate/heavy drinkers (>98 g/week) was 18.3 % and 35.6 %, respectively (P < 0.001). In age>60 years patients, the overall CFR in moderate/heavy drinker groups were as high as 53.4 % (95 % CI:40.2 %-66.7 %). Comparing to the age≤60y and non/light drinkers, age>60y and moderate/heavy drinkers was associated with increased risk of death with an odds ratio (95 % CI) of 9.9 (5.1-19.1). The interaction between age>60 and alcohol consumption was a significant determinant for death in both genders (F=10.18, P = 0.001). The clinical manifestation, laboratory parameters, and organ injury were significantly extensive and severe in moderate and heavy drinkers. In conclusion, hazardous alcohol consumption and aging synergistically increase the risk of death in patients with SFTS. In SFTS endemic areas, it is important for older individuals to minimize the exposure risks and abstain from alcohol., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure. Ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric ganglia. By immunohistochemistry, RNAscope in situ hybridization, transmission electron microscopy, and confocal microscopy, we confirmed that CD68+ macrophages are the target cells for EBOV in affected ganglia. Further, we demonstrated that EBOV can induce satellite cell and neuronal apoptosis and microglial activation in infected ganglia. Our results demonstrate that EBOV can infect peripheral ganglia and results in ganglionopathy in rhesus macaques, which may contribute to the neurological signs and symptoms observed in acute and convalescent Ebola virus disease in human patients., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Hydrogen sulfide, which can be generated in the central nervous system from the sulfhydryl-containing amino acid, L-cysteine, by cystathionine-β-synthase, may exert protective effects in experimental subarachnoid hemorrhage; however, the mechanism underlying this effect is unknown. This study explored the mechanism using a subarachnoid hemorrhage rat model induced by an endovascular perforation technique. Rats were treated with an intraperitoneal injection of 100 mM L-cysteine (30 μL) 30 minutes after subarachnoid hemorrhage. At 48 hours after subarachnoid hemorrhage, hematoxylin-eosin staining was used to detect changes in prefrontal cortex cells. L-cysteine significantly reduced cell edema. Neurological function was assessed using a modified Garcia score. Brain water content was measured by the wet-dry method. L-cysteine significantly reduced neurological deficits and cerebral edema after subarachnoid hemorrhage. Immunofluorescence was used to detect the number of activated microglia. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of interleukin 1β and CD86 mRNA in the prefrontal cortex. L-cysteine inhibited microglial activation in the prefrontal cortex and reduced the mRNA levels of interleukin 1β and CD86. RT-PCR and western blot analysis of the complement system showed that L-cysteine reduced expression of the complement factors, C1q, C3α and its receptor C3aR1, and the deposition of C1q in the prefrontal cortex. Dihydroethidium staining was applied to detect changes in reactive oxygen species, and immunohistochemistry was used to detect the number of NRF2- and HO-1-positive cells. L-cysteine reduced the level of reactive oxygen species in the prefrontal cortex and the number of NRF2- and HO-1-positive cells. Western blot assays and immunohistochemistry were used to detect the protein levels of CHOP and GRP78 in the prefrontal cortex and the number of CHOP- and GRP78-positive cells. L-cysteine reduced CHOP and GRP78 levels and the number of CHOP- and GRP78-positive cells. The cystathionine-β-synthase inhibitor, aminooxyacetic acid, significantly reversed the above neuroprotective effects of L-cysteine. Taken together, L-cysteine can play a neuroprotective role by regulating neuroinflammation, complement deposition, oxidative stress and endoplasmic reticulum stress. The study was approved by the Animals Ethics Committee of Shandong University, China on February 22, 2016 (approval No. LL-201602022)., Competing Interests: None

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of "omics" strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

Genotype-matched vaccines provide ideal protection against infection caused by new Newcastle disease virus (NDV) genotypes or variants even in the vaccinated chickens. In this study, we report a protocol for attenuation and rapid development of a velogenic NDV isolate as an effective vaccine candidate, using a simple and reliable infectious cloning platform. Based on DHN3, a genotype VII velogenic NDV isolate, recombinant rDHN3 was rescued by co-transfection of plasmids expressing the genomic RNA, NDV proteins NP, P and L, and the T7 polymerase without using a helper virus. Subsequently, an attenuated strain rDHN3-mF was produced by substitution of residues from amino acids 112 to 117 in the DHN3 F protein with the corresponding sequence from the LaSota strain. Both rDHN3 and rDHN3-mF are genetically stable during propagation in cell culture and chicken embryos. Further characterization through determination of EID 50 , MDT and clinical assessments confirmed that rDHN3 is velogenic and rDHN3-mF lentogenic. Vaccination of one-week-old SPF chicks with inactivated rDHN3-mF produced much higher anti-DHN3 antibody response and better protection against live DHN3 challenge than did the commercial LaSota vaccine, providing 100% protection and much earlier viral clearance. This attenuated NDV isolate would merit further development into a vaccine product., (Copyright © 2020 Wang, Huang, Fung, Luo, Ye, Du, Wen, Liu and Chen.)

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection is not well characterized in human patients or animal models. Through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Furthermore, histologic analysis, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy showed that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques. A time course of infection study with Ebola virus/Kikwit found that the large joint synovium became immunopositive beginning on postinfection day 6. In total, the synovium of 28 of 30 rhesus macaques with terminal filovirus disease had evidence of infection (64 of 96 joints examined). On the basis of immunofluorescence, infected cell types included CD68 + type A (macrophage-like) synoviocytes and CD44 + type B (fibroblast-like) synoviocytes. Cultured primary human fibroblast-like synoviocytes were permissive to infection with Ebola and Marburg viruses in vitro. Because synovial joints include immune privileged sites, these findings are significant for future investigations of filovirus pathogenesis and persistence as well as arthralgias in acute and convalescent filovirus disease., (Published by Elsevier Inc.)

Coronaviruses (CoVs) are enveloped (+) ssRNA viruses of veterinary and medical importance. Because recombinant CoVs with reporter proteins fused with viral proteins are usually non-viable or unstable, a small and quantifiable epitope tag would be beneficial to CoV research. In this study, we integrated the NanoLuc Binary Technology to the reverse genetics of infectious bronchitis virus (IBV), a prototypic gammacoronavirus. The 11-amino-acid HiBiT tag was inserted to the spike (S) or membrane (M) protein, and the recombinant IBVs (rS-HiBiT and rM-HiBiT) were characterized. Compared with the rIBV-p65 control, rS-HiBiT exhibited comparable growth kinetics, whereas rM-HiBiT replicated slightly slower. The levels of HiBiT-tagged S and M proteins in the infected cells or the culture supernatant could be both rapidly (~15 min) and efficiently (30 μL sample volume) determined using the HiBiT luminescence assay. Notably, replication of the HiBiT-tagged IBV could be monitored continuously in an infected chicken embryo, and rS-HiBiT was genetically stable for at least 20 passages. By integrating the HiBiT tagging system with CoV reverse genetics, this new reporter system may facilitate future study of CoV replication and pathogenesis., (Copyright © 2020 Liang, Zhu, Liang, Liu, Liu and Fung.)

Duck Tembusu virus (DTMUV) infection has caused great economic losses to the poultry industry in China, since its first discovery in 2010. Understanding of host anti-DTMUV responses, especially the innate immunity against DTMUV infection, would be essential for the prevention and control of this viral disease. In this study, transcriptomic analysis of duck embryonic fibroblasts (DEFs) infected with DTMUV reveals that several innate immunity-related pathways, including Toll-like, NOD-like, and retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways, are activated. Further verification by RT-qPCR confirmed that RIG-I, MAD5, TLR3, TLR7, IFN-α, IFN-β, MX, PKR, MHCI, MHCII, IL-1β, IL-6, (IFN-regulatory factor 1) IRF1, VIPERIN, IFIT5, and CMPK2 were up-regulated in cells infected with DTMUV. Through overexpression and knockdown/out of gene expression, we demonstrated that both VIPERIN and IRF1 played an important role in the regulation of DTMUV replication. Overexpression of either one significantly reduced viral replication as characterized by reduced viral RNA copy numbers and the envelope protein expression. Consistently, down-regulation of either one resulted in the enhanced replication of DTMUV in the knockdown/out cells. We further proved that IRF1 can up-regulate VIPERIN gene expression during DTMUV infection, through induction of type 1 IFNs as well as directly binding to and activation of the VIPERIN promoter. This study provides a genome-wide differential gene expression profile in cells infected with DTMUV and reveals an important function for IRF1 as well as several other interferon-stimulated genes in restricting DTMUV replication., (Copyright © 2020 Xiang, Huang, Xiong, Rong, Li, Liu and Chen.)

Background: Recent evidence showed that combining endoscopic submucosal dissection (ESD) and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer (EMGC) patients with risks of positive lymph node metastasis (pLNM)., Aim: To explore the predictive factors for pLNM in EMGC, and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC., Methods: Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016. Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors, providing odds ratio (OR) with 95% confidence interval. And the association between the number of predictors and the pLNM rate was also investigated., Results: Depth of invasion (OR = 7.342, 1.127-33.256, P = 0.039), tumor diameter (OR = 9.158, 1.348-29.133, P = 0.044), and lymphatic vessel involvement (OR = 27.749, 1.821-33.143, P = 0.019) turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis. For patients with 1, 2, and 3 risk factors, the pLNM rates were 9.1%, 33.3%, and 75.0%, respectively. pLNM was not detected in seven patients without any of these risk factors., Conclusion: ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size ≤ 2 cm, and when lymphatic vessel involvement is absent by postoperative histological examination. Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM., Competing Interests: Conflict-of-interest statement: No conflict of interest is declared by the authors., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal FAK/cortactin signals in vitro and in vivo. Consistently, all the levels of PRMT7, methylated SHANK2, FAK Y397 phosphorylation and cortactin Y421 phosphorylation were correlated with aggressive clinical breast cancer tissues. These findings characterize the PRMT7-dependent SHANK2 methylation as a key player in mediating endosomal FAK signals activation, also point to the value of SHANK2 R240 methylation as a target for breast cancer metastasis., Competing Interests: YL, LL, XL, YW, LL, LP, JL, LZ, GW, HL, DL, BH, JL, YZ No competing interests declared, (© 2020, Liu et al.)

Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation and the ratio of Bax to Bcl-2 in the ischemic brain. CAG also inhibited NF-κB p65 nuclear translocation. As a result, CAG suppressed the mRNA expression of pro-inflammatory cytokines, including TNF-α and IL-1β, and inhibited the activation of microglia and astrocytes in the ischemic brain. Our findings suggest that CAG is neuroprotective against ischemic brain injury in mice and that its beneficial effect may involve SIRT1 upregulation and the inhibition of apoptosis and neuroinflammation in the ischemic brain.

Mastication and saliva addition affects the formation of a bolus, directly playing a key role in people's eating enjoyment. However, the specific changes of oral physiological parameters and bolus moisture content in the oral processing of rice have not been studied in detail. Thus, in the present study, salivary flow rate, salivary secretion, chewing frequency, and bolus moisture content during oral processing of three rice varieties (japonica rice, indica rice, and glutinous rice) were fully investigated. The differences among different rice and changes among different oral processing stages (25%, 50%, 75%, and 100%) were analyzed. Results showed that the swallowing time of glutinous rice was significantly lower than that of japonica and indica rice (p < .05). However, there was no significant difference in the chewing frequency of the three rice varieties throughout the oral processing stages (1.59-1.66 Hz, p > .05). During oral processing, the salivary flow rates for the three kinds of rice decreased significantly (p < .05), from 37.72 ± 4.32 mg/s (0%-25% stage) to 19.83 ± 5.50 mg/s (75%-100% stage). The dry basis moisture content of the bolus increased significantly (p < .05), from 1.53 ± 0.08 (0%) to 1.96 ± 0.02 (100%). In the 75%-100% stage, the amount of saliva secretion for japonica rice was highest, followed by indica rice and glutinous rice (p < .05). At the point of swallowing (100% stage), the dry basis moisture content of all three rice-bolus' was consistent (1.94-1.99, p > .05)., (© 2020 Wiley Periodicals, LLC.)

Two new species of Episymploce Bey-Bienko from China are described. Nine individuals of E. sichuanensis sp. nov . were collected from Sichuan Province and four individuals of E. maxima , sp. nov . were collected from Guangxi Province. Morphology, especially the wings, specialized abdominal tergum and genitalia of adults, are described and illustrated in detail. Episymploce sichuanensis sp. nov. is similar to E. kunmingi (Bey-Bienko, 1969), but can be easily distinguished by the reduced wings, bifurcated two processes at the hind margin of the supra-anal plate, and the unspecialized first abdominal tergum (T1). Episymploce maxima sp. nov. is similar to E. taiheizana Asahina, 1979 but is distinguished by its large size, the lateromedial margins of the subgenital plate without processes, and the unspecialized T1. A key to the recorded Episymploce species from China is provided in this paper., (Ting-Ting Li, De-Xing Liu, De-Yi Qiu, Qiao-Yun Yue.)

Objective: To compare clinical effects of common Kirschner wire, anatomical plate and perforated Kirschner wire in treating olecranon fracture., Methods: From March 2014 to May 2017, clinical data of 79 patients with olecranon fracture treated with different internal fixation was retrospectively analyzed. Among them, 26 patients treated with common Kirschner wire (group A), including 19 males and 7 females aged from 23 to 51 years old with an average of (37.2±9.6) years old;11 patients were typeⅠ, and 15 patients were typeⅡ according to Mayo classification. Twenty eight patients were treated with olecroanon anatomical plate internal fixation, including 16 males and 12 females aged from 25 to 52 years old with an average of (36.6±8.9) years old;10 patientswere typeⅠ and 18 patients were typeⅡ according to Mayo classification. Twenty five patients were treated with perforated Kirschner wire, including 13 males and 12 females aged from 26 to 51 years old with an average of (38.2±9.2) years old;9 patients were typeⅠand 16 patients were typeⅡ according to Mayo classification. Operation time, intraoperatve blood loss, fracture healing time and postoperative complications among three groups were compared; VAS score at 1 week after operation was used to evaluate pain relief, Broberg-Morrey function score of elbow joint at the final follow up was applied to evaluate clinical effect., Results: Seventy nine patients were followed up from 13 to 23 months with an average of (18.3±4.5) months. Operation time, intraoperatve blood loss, fracture healing time in group A were (82.9±19.7) min, (113.5±32.3) ml, (4.2±0.6) months respectively;in group B were(101.2±24.5) min, (150.2±39.5) ml, (4.6±0.8) months respectively;in group C were (83.3±18.7) min, (119.3±34.3) ml, (4.1±0.5) months respectively. Operation time, intraoperatve blood loss, fracture healing time in group A and group C were better than that of group B( P <0.05). Five patients in group A occurred ineffective internal fixation, other groups did not occurred;9 patients in group A occurred skin irritability, 3 patients in group B and no patient occurred in group C; there were statistical differences in complications among three groups ( P <0.05). There were no differences in VAS score at 1 week after operation and Broberg-Morrey function score of elbow joint at the final follow-up among three groups ( P >0.05)., Conclusion: Common Kirschner wire has more complications; anatomical plate has greater surgical trauma and long fracture healing time;while perforated Kirschner wire was not only benefit for fracture union with less trauma, but also could reducing the incidence of postoperative complications, and it is the appropriate method for patients with olecranon fracture.

Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013-2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not.

Sperm-associated Antigen 5 (SPAG5) is a mitotic spindle protein. Recent studies have found that it is overexpressed in many human cancers and functions as an oncogene. Here, we summarize the current underlying mechanisms for its oncogenic roles in regulating cellular behaviors of cancer cells and discuss the possibility of targeting SPAG5 for cancer treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Zaire ebolavirus (EBOV) causes Ebola virus disease (EVD), which carries a fatality rate between 25% and 90% in humans. Liver pathology is a hallmark of terminal EVD; however, little is known about temporal disease progression. We used multiplexed fluorescent immunohistochemistry and in situ hybridization in combination with whole slide imaging and image analysis (IA) to quantitatively characterize temporospatial signatures of viral and host factors as related to EBOV pathogenesis. Eighteen rhesus monkeys euthanized between 3 and 8 days post-infection, and 3 uninfected controls were enrolled in this study. Compared with semiquantitative histomorphologic ordinal scoring, quantitative IA detected subtle and progressive features of early and terminal EVD that was not feasible with routine approaches. Sinusoidal macrophages were the earliest cells to respond to infection, expressing proinflammatory cytokine interleukin 6 (IL6) mRNA, which was subsequently also observed in fibrovascular compartments. The mRNA of interferon-stimulated gene-15 (ISG-15), also known as ISG15 ubiquitin like modifier (ISG15), was observed early, with a progressive and ubiquitous hybridization signature involving mesenchymal and epithelial compartments. ISG-15 mRNA was prominent near infected cells, but not in infected cells, supporting the hypothesis that bystander cells produce a robust interferon gene response. This study contributes to our current understanding of early EVD progression and illustrates the value that digital pathology and quantitative IA serve in infectious disease research., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 ( CR2 ), nitric oxide synthase 3 ( NOS3 ), collagen type II alpha 1 chain ( COL2A1 ), protein tyrosine phosphatase non-receptor type 22 ( PTPN22 ), and transient receptor potential cation channel subfamily V member 4 ( TRPV4 ) were reported to be involved in this process., Aim: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes., Methods: SNVs in the CR2 , NOS3 , COL2A1 , PTPN22 , and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows-wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs., Results: Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S)., Conclusion: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1 , and CR2 ., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To evaluate the clinical outcomes of on-pump total arterial revascularization with bilateral radial artery (BRA) and left internal mammary artery (LIMA) as conduits in coronary artery bypass grafting (CABG) patients with left ventricular dysfunction (LVD). Methods: All the perioperative medical records and follow-up results of coronary artery disease patients with left ventricular ejection fraction (LVEF) ≤ 40% undergoing CABG from 24 heart centers of 15 provinces and autonomous regions in China between July 2015 and December 2019 were retrospectively analyzed. Results: A total of 87 consecutive patients (55 males and 32 females) underwent on-pump CABG with BRA and LIMA, with a mean age of (57.5±9.1) years old. There were 22 patients complicated with primary hypertension, 12 with diabetes mellitus, 8 with peripheral vascular disease, 7 with chronic obstructive lung disease, 12 with mild renal injury and 3 with partial aortic calcification. There were 43 cases with in-stent stenosis, and 21 had left main disease. The mean LVEF and left ventricular end-diastolic diameter (LVEDD) was (35.5±7.3)% and (65.5±2.6) mm, respectively. The mean graft number, aortic cross-clamp time and cardiopulmonary bypass duration was 3.2±0.9, (90.5±22.7) min and (113.4±19.2) min, respectively. There were 32 mitral and 9 aortic valve replacements, and 5 tricuspid annuloplasties. Prophylactic intra-aortic balloon pumps were implanted in 27 patients. There were 2 operative deaths from acute heart failure. After surgery, there were 15 cases of atrial fibrillation, 1 case of acute kidney injury, 1 case of acute myocardial infarction, and 1 cases of stroke. All the patients fulfilled the follow-up, with a mean time of (39.5±7.7) months. At 3 months after surgery, LVEDD was decreased and LVEF was improved significantly compared with pre-operative indicators [(53.0±1.5) mm vs (65.5±2.6) mm, t= 9.51 P= 0.02; (45.2±3.3)% vs (35.5±7.3)%, t= 13.79, P= 0.001]. No major cardiac events were reported during the follow-up. At (30.5±7.4) months after surgery, 62.4% of patients (53/85) underwent coronary CT angiography examination, and the results indicated that the graft patency was 98.8%, with only one case of RA occlusion occurred. Conclusion: In selected patients of LVD, on-pump total arterial revascularization with BRA and LIMA conduits was proved to be safe and effective.

Recent experimental study shows that the pre-lithiated MoS 2 monolayer exhibits an enhanced electrochemical performance, coulombic efficiency of which is 26% higher than the pristine MoS 2 based anode. The underlying mechanism of such significant enhancement, however, has not yet been addressed. By means of density functional theory (DFT) calculations, we systematically investigated the adsorption and diffusion behavior of lithium (Li) atoms on the MS 2 (M = Mo, W, V) monolayers. On the pre-lithiated MS 2 monolayers, the adsorption energy of extra Li ions are not significantly changed, implying the feasibility of multilayer adsorption. Of importance, the Li diffusion barriers on pre-lithiated MS 2 are negligibly small because of the charge accumulation between the diffusing Li ions and the pre-lithiating Li layer. Correspondingly, we report that the pre-lithiation should be a general treatment which can be employed on many transition-metal di-chalcogenides to improve their storage capacities and charge-discharge performance in Li ion batteries. In addition, we propose that the pre-lithiated VS 2 may serve as an outstanding anode material in LIBs.

Two new compounds were obtained by assembling the [(2-methoxy-5-nitro-anilinium)(18-crown-6)]+ cation with non-polar PF6- and polar SO3CF3- anions, respectively. Benefiting from its polar anion, the SO3CF3- compound reveals a more significant dielectric switching behaviour during phase transition, demonstrating an effective strategy to enhance the dielectric property by adding polar components.

Lassa virus (LASV) poses a significant public health problem within the regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding intergenic region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication. IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding intergenic region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

The expression of contactin-associated protein 1 (Caspr1) in brain microvascular endothelial cells (BMECs), one of the major cellular components of the neurovascular unit (NVU), has been revealed recently. However, the physiological role of Caspr1 in BMECs remains unclear. We previously reported the nonamyloidogenic processing of amyloid protein precursor (APP) pathway in the human BMECs (HBMECs). In this study, we found Caspr1 depletion reduced the levels of soluble amyloid protein precursor α (sAPPα) in the supernatant of HBMECs, which could be rescued by expression of full-length Caspr1. Our further results showed that ADAM9, the α-secretase essential for processing of APP to generate sAPPα, was decreased in Caspr1-depleted HBMECs. The reduced sAPPα secretion in Caspr1-depleted HBMECs was recovered by expression of exogenous ADAM9. Then, we identified that Caspr1 specifically regulates the expression of ADAM9, but not ADAM10 and ADAM17, at transcriptional level by nuclear factor-κB (NF-κB) signaling pathway. Caspr1 knockout attenuated the activation of NF-κB and prevented the nuclear translocation of p65 in brain endothelial cells, which was reversed by expression of full-length Caspr1. The reduced sAPPα production and ADAM9 expression upon Caspr1 depletion were effectively recovered by NF-κB agonist. The results of luciferase assays indicated that the NF-κB binding sites are located at -859 bp to -571 bp of ADAM9 promoter. Taken together, our results demonstrated that Caspr1 facilitates sAPPα production by transcriptional regulation of α-secretase ADAM9 in brain endothelial cells., (Copyright © 2020 Tang, Liu, Li, Wang, Wang, Su, Fang, Qin, Wei, Zhao and Chen.)

Introduction: The purpose of this study was to comparatively evaluate the effects of Twin-block (TB) appliance and sagittal-guidance Twin-block (SGTB) appliance on alveolar bone around mandibular incisors in growing patients with Class II Division 1 malocclusion, using cone-beam computed tomography., Methods: The sample consisted of 25 growing patients with Class II Division 1 malocclusion (14 boys and 11 girls, mean age 11.92 ± 1.62 years) and was randomly distributed into the TB group (n = 13) and the SGTB group (n = 12). The treatment duration was 11.56 ± 1.73 months. Pretreatment (T1) and posttreatment (T2) cone-beam computed tomography scans were taken in both groups. Height, thickness at apex level, and volume of the alveolar bone around mandibular left central incisors were measured respectively on labial and lingual side, using Mimics software (version 19.0; Materialise, Leuven, Belgium). Based on the stable structures, 3-dimensional (3D) registrations of T1 and T2 models were taken to measure the sagittal displacement of incisors. Intragroup comparisons were evaluated by paired-samples t tests and Wilcoxon tests. Independent-samples t tests and Mann-Whitney U tests were used for intergroup comparisons., Results: In both groups, alveolar bone height and volume on the labial side of the incisors significantly decreased after treatment (P <0.05). Lingual alveolar bone height, lingual and total alveolar bone volume, labial, lingual and total alveolar bone thickness showed no significant difference between T1 and T2 (P >0.05). In both groups the incisors tipped labially and drifted to the labial side. Compared with the TB group, less labial alveolar bone loss, less incisor proclination and crown edge drift were found in the SGTB group (P <0.05)., Conclusions: Labial alveolar bone loss around mandibular incisors was observed after both types of appliances treatment in growing patients with Class II Division 1 malocclusion. Less labial alveolar bone loss, less incisor proclination, and crown edge drift were found in the SGTB group than in the TB group during treatment., (Copyright © 2019 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Lassa virus (LASV) is endemic in Western Africa and is estimated to infect hundreds of thousands of individuals annually. A considerable number of these infections result in Lassa fever (LF), which is associated with significant morbidity and a case-fatality rate as high as 69% among hospitalized confirmed patients. U.S. Food and Drug Administration-approved LF vaccines are not available. Current antiviral treatment is limited to off-label use of a nucleoside analogue, ribavirin, that is only partially effective and associated with significant side effects. We generated and characterized a recombinant LASV expressing a codon-deoptimized (CD) glycoprotein precursor gene (GPC), rLASV-GPC/CD. Comparison of growth kinetics and peak titers showed that rLASV-GPC/CD is slightly attenuated in cell culture compared to wild-type (WT) recombinant LASV (rLASV-WT). However, rLASV-GPC/CD is highly attenuated in strain 13 and Hartley guinea pigs, as reflected by the absence of detectable clinical signs in animals inoculated with rLASV-GPC/CD. Importantly, a single subcutaneous dose of rLASV-GPC/CD provides complete protection against an otherwise lethal exposure to LASV. Our results demonstrate the feasibility of implementing a CD approach for developing a safe and effective LASV live-attenuated vaccine candidate. Moreover, rLASV-GPC/CD might provide investigators with a tool to safely study LASV outside maximum (biosafety level 4) containment, which could accelerate the elucidation of basic aspects of the molecular and cell biology of LASV and the development of novel LASV medical countermeasures. IMPORTANCE Lassa virus (LASV) infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever (LF) cases. Licensed LF vaccines are not available, and anti-LF therapy is limited to off-label use of the nucleoside analog ribavirin with uncertain efficacy. We describe the generation of a novel live-attenuated LASV vaccine candidate. This vaccine candidate is based on mutating wild-type (WT) LASV in a key region of the viral genome, the glycoprotein precursor (GPC) gene. These mutations do not change the encoded GPC but interfere with its production in host cells. This mutated LASV (rLASV-GPC/CD) behaves like WT LASV (rLASV-WT) in cell culture, but in contrast to rLASV-WT, does not cause disease in inoculated guinea pigs. Guinea pigs immunized with rLASV-GPC/CD were protected against an otherwise lethal exposure to WT LASV. Our results support the testing of this candidate vaccine in nonhuman primate models ofLF., (Copyright © 2020 Cai et al.)

MR pulmonary angiography (MRPA) combined with indirect MR venography (MRV) was attempted by using 3D contrast-enhanced MR volume interpolated body examination (VIBE) sequence. Agreement rate for deep venous thrombosis (DVT) detection between MRV and duplex sonography (DUS) was evaluated; the potential of this method for venous thromoembolism (VTE) was also investigated. Thirty-four patients with DUS-identified DVT were enrolled in this study. MRI was performed after a single administration of Gadopentetate dimeglumine. Fat-suppressed 3D VIBE was applied for visualizing pulmonary arteries, abdominal veins, pelvic and leg veins, ranging from lung apex to ankle level. Two radiologists observed the MR images in consensus, recorded the location and number of emboli. MRV images were assessed based on per-vein segment. The agreement rate between MRV and DUS for venous segment-to-segment comparison was analyzed by Wilcoxon rank sum test. All the patients were diagnosed as having DVT by MRV. MRV detected 55 more venous segments with thrombi than DUS based on per-vein segment analysis. Twenty-three patients with pulmonary embolism (PE) were detected by MRPA. Twenty-one patients underwent both pulmonary CT angiography and MRPA, and consistency for PE detection was 100%. Total examination time of the combined MR protocol was 7 min for each patient. The contrast-enhanced VIBE sequence proves to be a feasible and reliable method for VTE diagnosis in one-stop MR scanning procedure, and contrast-enhanced VIBE performs better to depict DVT than DUS on per-vein segment basis.

Coronavirus (CoV) envelope (E) protein is a small structural protein critical for virion morphogenesis and release. The recently characterized E protein ion channel activity (EIC) has also been implicated in modulating viral pathogenesis. In this study, we used infectious bronchitis coronavirus (IBV) as a model to study EIC. Two recombinant IBVs (rIBVs) harboring EIC-inactivating mutations - rT16A and rA26F - were serially passaged, and several compensatory mutations were identified in the transmembrane domain (TMD). Two rIBVs harboring these putative EIC-reverting mutations - rT16A/A26V and rA26F/F14N - were recovered. Compared with the parental rIBV-p65 control, all four EIC mutants exhibited comparable levels of intracellular RNA synthesis, structural protein production, and virion assembly. Our results showed that the IBV EIC contributed to the induction of ER stress response, as up-regulation of ER stress-related genes was markedly reduced in cells infected with the EIC-defective mutants. EIC-defective mutants also formed smaller plaques, released significantly less infectious virions into the culture supernatant, and had lower levels of viral fitness in cell culture. Significantly, all these defective phenotypes were restored in cells infected with the putative EIC revertants. EIC mutations were also implicated in regulating IBV-induced apoptosis, induction of pro-inflammatory cytokines, and viral pathogenicity in vivo . Taken together, this study highlights the importance of CoV EIC in modulating virion release and various aspects of CoV - host interaction., (Copyright © 2020 Li, Yuan, Dai, Chen, Liu and Fung.)

Background : Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. Methods : In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. Four patients are locally advanced and four are metastatic. All the patients received at least two doses of PD-1 antibody with or without chemotherapy as neoadjuvant therapy. The aim of the present study was to evaluate the short-term efficacy and toxicities of this strategy. Results : All the enrolled eight patients had a major response in imaging and/or pathological evaluation. Five of the seven resected patients were evaluated as pathological complete response. One patient without surgery has a clinical complete response (cCR) tumor response. Conclusions : Neoadjuvant PD-1 blockade induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H colorectal cancer. Further studies are required to evaluate the long-term effect of this strategy., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Ketamine has gained increasing popularity in adolescent drug abusers worldwide. However, relatively little is known about the long-term effects of recreational ketamine on adolescent hippocampus. The present study investigates the effects of different periods (1, 3 and 6 months) of recreational ketamine administration on locomotor activity and neuron damage in the hippocampus of adolescent cynomolgus monkeys. 32 4-year-old male cynomolgus monkeys were divided into control, 1-month, 3-month and 6-month groups. All animals in ketamine groups received daily intravenous injection with 1 mg/kg ketamine in saline for respective 1, 3 or 6 months while control group received normal saline. Automatic behaviors were recorded for 10 min before and after ketamine and saline administration. Meanwhile, the markers of apoptosis in the hippocampus were assessed using terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL), electron microscopy and western blotting. Results showed that ketamine significantly decreased locomotor activity, increased apoptotic neurons and pro-apoptotic proteins, cleaved Caspase-3 and Bax, while decreased the anti-apoptotic protein Bcl-2 in the hippocampus after 6-month ketamine administration. Our study suggested that chronically recreational ketamine might induce hypolocomotion and neurotoxic effect via apoptotic pathway in adolescent hippocampus of monkeys., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study aimed to investigate the clinical effects of the brand new perioperative transfusion trigger score (POTTS) system in patients undergoing malignant tumor surgeries. 442 cases of patients diagnosed with malignant tumor were randomly selected (from January 2012 to December 2016) from Zunyi Medical University and were divided into 3 experimental groups. Patients in the POTTS group were transfused by the POTTS guideline perioperatively, while patients in the 7-10 g group were treated by the traditional transfusion guidelines existed (restrictive transfusion strategy), patients in the 10 g group should be transfused to keep the Hb level no less than 10 g/dL (liberal transfusion strategy). Baseline information, operation time, bleeding volume, transfusion amount, incision healing time, postoperative complications, metastasis and recurrence were observed and recorded. Postoperative short-term mortality was comparable of the 3 groups, 3 cases of death all occurred in 10 g group, there was no significant difference in the incidence of postoperative complications, including infectious complications and coagulation related complications. Follow-up to date, there were 25 cases, 29 cases and 29 cases of tumor recurrence and metastasis in the three groups, but no statistical difference observed. The present findings show that the POTTS transfusion system is more advantageous with regard to save blood and relieve economic burdens of patients, and does not affect the long-term recurrence and metastasis rate of malignant tumor., (© Indian Society of Hematology and Blood Transfusion 2019.)

Rhesus macaques are physiologically similar to humans and, thus, have served as useful animal models of human diseases including cardiovascular disease. The purpose of this study was to characterize the distribution, composition, and phenotype of macrophages in heart tissues of very young (fetus: 0.5 years, n = 6), young adult (2-12 years, n = 12), and older adult (13-24 years, n = 9) rhesus macaques using histopathology and immunofluorescence microscopy. Results demonstrated that macrophages were uniformly distributed throughout the heart in animals of all age groups and were more prevalent than CD3-positve T-cells and CD20-positive B-cells. Macrophages comprised approximately 2% of heart tissue cells in the younger animals and increased to a mean of nearly 4% in the older adults. CD163-positive macrophages predominated over HAM56-positive and CD206-positive macrophages, and were detected at significantly higher percentage in the animals between 13 and 24 years of age, as well as in heart tissues exhibiting severe histopathology or inflammation in animals of all age groups. In vivo dextran labeling and retention indicated that approximately half of the macrophages were longer lived in healthy adult heart tissues and may comprise the tissue-resident population of macrophages. These results provide a basis for continued studies to examine the specific functional roles of macrophage subpopulations in heart tissues during homeostasis and in cardiovascular disease for then developing intervention strategies., (©2019 Society for Leukocyte Biology.)

Cerebral angiogenesis is a key event during brain development and recovery from brain injury. We previously demonstrated that Atg7 knockout impaired angiogenesis in the mouse brain. However, the role of Atg7 in angiogenesis is not completely understood. In this study, we used human brain microvascular endothelial cells (HBMECs) to investigate the mechanism of Atg7-regulated cerebral angiogenesis. We found that Atg7 depletion specifically diminished the expression of the β3 and γ2 chains of laminin-5, a major component of the extracellular matrix. In contrast, autophagy inhibitors did not affect laminin-5 expression, suggesting that Atg7-regulated laminin-5 expression is autophagy-independent. We also found that Atg7-regulated laminin-5 expression occurred at the transcriptional level through NF-κB signaling. Exogenous laminin-5 or the NF-κB agonist betulinic acid effectively rescued tube formation by Atg7-deficient HBMECs. Taken together, our study identified a novel mechanism by which Atg7 regulates laminin-5 expression via NF-κB to modulate tube formation by brain endothelial cells during cerebral angiogenesis. Anat Rec, 302:2255-2260, 2019. © 2019 American Association for Anatomy., (© 2019 American Association for Anatomy.)

The solid dispersion technique, which is widely used in the medical field, was applied to prepare a pesticide dosage form of emamectin benzoate (EM). The preparation, physicochemical characterization, aqueous solubility, release dynamics, photolytic degradation, bioactivity, and sustained-release effects of the prepared EM solid dispersions were studied by a solvent method, using polymer materials as the carriers. Water-soluble polyvinyl pyrrolidone (PVP) K30 and water-insoluble polyacrylic resin (PR)III were used as the carriers. The influence of various parameters, such as different EM:PVP-K30 and EM:PRIII feed ratios, solvent and container choices, rotational speed and mixing time effects on pesticide loading, and the entrapment rate of the solid dispersions were investigated. The optimal conditions for the preparation of EM-PVP-K30 solid dispersions required the use of methanol and a feed ratio between 1:1 and 1:50, along with a rotational speed and mixing time of 600 rpm and 60 min, respectively. For the preparation of EM-PRIII solid dispersions, the use of methanol and a feed ratio between 1:4 and 1:50 were required, in addition to the use of a porcelain mortar for carrying out the process. Under optimized conditions, the prepared EM-PVP-K30 solid dispersions resembled potato-like, round, and irregular structures with a jagged surface. In contrast, the EM-PRIII solid dispersions were irregular solids with a microporous surface structure. The results of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), ultraviolet (UV) spectrometry, and infrared (IR) spectrometry showed that the solid dispersions were formed by intermolecular hydrogen bonding. The solid dispersion preparation in PVP-K30 significantly improved the solubility and dissolution rate of EM, particularly the aqueous solubility, which reached a maximum of 37.5-times the EM technical solubility, when the feed ratio of 1:10 was employed to prepare the dispersion. Importantly, the wettable powder of EM-PVP-K30 solid dispersion enhanced the insecticidal activity of EM against the Plutella xylostella larvae. Furthermore, the solid dispersion preparation in PRIII afforded a significant advantage by prolonging the EM technical release in water at a pH below 7.0, especially when the PRIII content in solid dispersions was high. While the amplified toxicity of the wettable powder of EM-PRIII solid dispersions against the P. xylostella larvae showed no significant differences from that of the EM technical, the long-term toxicity under the field condition was much better than that of the commercially available EM 1.5% emulsifiable concentrate. Notably, solid dispersions with both the PVP-K30 and PRIII carriers reduced the effect of UV photolysis.

Objective: To understand the etiology of hepatopathy of unknown etiology in patients undergoing liver biopsy. Methods: Demographic data and pathological examination reports of patients with hepatopathy of unknown etiology who underwent liver biopsy examination at outpatient and inpatient of the Second Hospital of Nanjing between January 2017 and June 2018 were retrospectively collected. All liver histopathological sections combined with clinical and pathological features based on liver biopsy examinations were diagnosed by a reputed clinician and a pathologist. Results: A total of 470 cases with hepatopathy of unknown etiology who underwent liver biopsy were enrolled. Of these, 425 cases (90.4%) had a definite diagnosed disease after comprehensive analysis of pathological and clinical data. The diagnosis of hepatopathy of unknown etiology included 11 diseases: 90 cases with autoimmune hepatitis had autoimmune liver disease (19.1%), 38 cases had primary biliary cholangitis (8.1%), 43 cases with overlap syndrome of autoimmune hepatitis had primary biliary cholangitis (9.1%), 118 cases had drug-induced liver injury (25.1%), 75 cases had nonalcoholic fatty liver disease (NAFLD) (16.0%), 12 cases had alcoholic liver disease (2.6 cases) %), 15 cases (3.2%) had vascular liver disease, 7 cases (1.5%) had hereditary metabolic liver disease, 5 cases (1.1%) had other systemic diseases, 16 cases (3.4%) had more than two kinds of liver diseases, and 6 cases (1.3%) had others rare liver diseases. Conclusion: Over 90% cause of the hepatopathy of unknown etiology in the long run can be determined, and the main causes are autoimmune liver disease, drug-induced liver injury, and nonalcoholic fatty liver disease, which needs multidisciplinary cooperation to diagnose, and clinicians need to master the basic and clinical knowledge of liver diseases as well as liver pathology, hepatobiliary imaging, and genetics.

Objective: To evaluate the mid-term outcomes of coronary artery bypass grafting (CABG) with left radial artery (RA) graft bypassed to right main coronary artery (RCA) of severe stenosis. Methods: Between September 2014 and April 2019, a total of consecutive 47 patients who had severe stenosis (≥90%) of RCA underwent total arterial revascularization, with left RA bypassed to RCA. There were 31 males and 16 females, with a mean age of (56.5±9.7) years old. The perioperative outcomes were observed and mid-term results were followed up. Results: A total of 46 left internal mammary artery (LIMA) grafts, 47 left radial artery (LRA), and 40 right RA grafts (RRA) were harvested with pedicles. LIMA was bypassed to LAD in 43 patients, RRA was to diagonal branches, ramus or oblique marginal in 37 cases, and LRA was to RCA. All grafts (except 3 composite Y or T grafts) were single. Mean graft number was 2-4 (2.7±0.9). There was one death due to cardiac tamponade. Three patients had postoperative atrial fibrillation, 1 had a forearm hematoma, 1 had acute renal insufficiency, and 2 had acute myocardial infarction. The mean tracheal intubation duration was 3.5-20.3 (8.3±4.7) hours, and the mean hospital stay was 6-13 (7.1±2.9) days. The average follow-up was 3-47 (23.3±7.5) months, with a follow-up rate of 86.96% (40/46). There were no major cardiovascular events during the follow-up. Three month after surgery, the mean left ventricular ejection fraction was significantly improved than that of pre-operation (60.0%±4.0% vs 42.4%±7.5%, P= 0.003). Computed tomography angiography (CTA) examination showed that 58.7% (27/46) of patients had patent LRA after a mean follow-up duration of (19.5±7.3) months. Conclusion: CABG with LRA bypassed to RCA of severe stenosis proves to be safe and effective, with good mid-term outcomes.

Objective: This study was aimed to observe the effects of wireless audio microphone on hearing aids effect in noise at different listening distances. Method: Twenty-three subjects with bilateral sensorineural hearing loss, including 17 males and 6 females were fitted with binaural hearing aids. These patients did sentences recognition tests at two different listening distance（1.5 and 3 meters） in noise. The subjects were tested under three conditions, ①with hearing aids alone; ②with the wireless audio microphone alone; ③with hearing aid microphone and mini audio microphone simultaneously. Result: The sentence recognition threshold at 3 meters listening distance is significantly higher than it at 1.5 meters listening distance with hearing aids alone（ P <0.05）. There is no significant difference in the sentence recognition threshold between two listening distances when the wireless audio microphone was switched on（ P >0.05）. Conclusion: Mini audio microphone can significantly improve hearing aids effect in long distance listening in noise., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Our recent publications showed that multidrug resistance protein 2 (MRP2, encoded by the ABCC2 gene) conferred oxaliplatin resistance in human liver cancer HepG2 cells. However, the contribution of MRP2 to oxaliplatin resistance remains unclear in colorectal and pancreatic cancer lines. We investigated the effects of silencing MRP2 by siRNA on oxaliplatin accumulation and sensitivity in human colorectal cancer Caco-2 cells and pancreatic cancer PANC-1 cells. We characterized the effects of oxaliplatin on MRP2 ATPase activities using membrane vesicles. Over-expression of MRP2 (endogenously in Caco-2 and PANC-1 cells) was associated with decreased oxaliplatin accumulation and cytotoxicity, but those deficits were reversed by inhibition of MRP2 with myricetin or siRNA knockdown. Silencing MRP2 by siRNA increased oxaliplatin-induced apoptotic rate in Caco-2 and PANC-1 cells. Oxaliplatin stimulated MRP2 ATPase activity with a concentration needed to reach 50% of the maximal stimulation (EC 50 ) value of 8.3 ± 0.7 µM and Hill slope 2.7. In conclusion, oxaliplatin is a substrate of MRP2 with possibly two binding sites, and silencing MRP2 increased oxaliplatin accumulation and cytotoxicity in two widely available gastrointestinal tumour lines (PANC-1 and Caco-2).

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication of HCoV is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. Activation of critical signaling pathways during HCoV infection modulates the induction of antiviral immune response and contributes to the pathogenesis of HCoV. Recent studies have begun to reveal some fundamental aspects of the intricate HCoV-host interaction in mechanistic detail. In this review, we summarize the current knowledge of host factors co-opted and signaling pathways activated during HCoV infection, with an emphasis on HCoV-infection-induced stress response, autophagy, apoptosis, and innate immunity. The cross talk among these pathways, as well as the modulatory strategies utilized by HCoV, is also discussed.

Graphene is an attractive candidate for developing high conductivity materials (HCMs) owing to an extraordinary charge mobility. While graphene itself is a semi-metal with an inherently low carrier density, and methods used for increasing carrier density normally also cause a marked decrease in charge mobility. Here, we report that ordered nitrogen doping can induce a pronounced increase in carrier density but does not harm the high charge mobility of graphene nanoribbons (GNRs), giving rise to an unprecedented ultrahigh conductivity in the system. Our first-principles calculations for orderly N-doped GNRs (referred to as C 5 N-GNRs) show that N-doping causes a significant shift-up of the Fermi level (Δ E F ), resulting in the presence of multiple partially-filled energy bands (PFEDs) that primarily increase the carrier density of system. Notably, the PFEDs are delocalized well with integral and quantized transmissions, suggesting a negligible effect from N-doping on the charge mobility. Moreover, the PFEDs can cross the E F multiple times as the ribbon widens, causing the conductivity to increase monotonically and reach ultrahigh values (>15 G 0 ) in sub-5 nm wide ribbons with either armchair or zigzag edges. Furthermore, a simple linear relationship between the doing concentration and the Δ E F was obtained, which provides a robust means for controlling the conductivity of C 5 N-GNRs. Our findings should be useful for understanding the effect of ordered atomic doping on the conductivity of graphene and may open new avenues for realizing graphene-based HCMs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Understanding the influence of colloids on radionuclide migration is of significance to evaluate environmental risks for radioactive waste disposals. In order to formulate an appropriate modelling framework that can quantify and interpret the anomalous transport of Strontium (Sr) in the absence and presence of colloids, the continuous time random walk (CTRW) approach is implemented in this work using available experimental information. The results show that the transport of Sr and its recovery are enhanced in the presence of colloids. The causes can be largely attributed to the trap-release processes, e.g. electrostatic interactions of Sr, colloids and natural sediments, and differences in pore structures, which gave rise to the varying interstitial velocities of dissolved and, if any, colloid-associated Sr. Good agreement between the CTRW simulations and the column-scale observations is demonstrated. Regardless of the presence of colloids, the CTRW modelling captures the characteristics of non-Fickian anomalous transport (0 < β < 2) of Sr. In particular, a range of 0 < β < 1, corresponding to the cases with greater recoveries, reveal strongly non-Fickian transport with distinctive earlier arrivals and tailing effects, likely due to the physicochemical heterogeneities, i.e. the repulsive interactions and/or the macro-pores originating from local heterogeneities. The results imply that colloids can increase the Sr transport as a barrier of Sr sorption onto sediments herein, apart from often being carriers of sored radionuclides in aqueous phase. From a modelling perspective, the findings show that the established CTRW model is valid for quantifying the non-Fickian and promoted transport of Sr with colloids., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ketamine has become increasingly popular in adolescent drug abusers worldwide. Meanwhile, alcohol is usually used by ketamine users. However, little work has been conducted to examine the chronic combined effects of ketamine and ethanol on adolescent brain. Here we probed into the effects of chronic administration of ketamine at recreational doses alone or combined with ethanol on behaviors and neuron damage in an adolescent rat model. 28-day old rats were treated with either 20 or 30 mg/kg ketamine plus or not plus 10% ethanol daily for 21 days. Depressive like behaviors, anxiety like behavior and memory impairment were tested using open field test, forced swimming test, elevated plus maze and Morris water maze. Apoptosis in prefrontal cortex (PFC) and hippocampus (HIP) were determined by the TdT-mediated dUTP Nick-End Labeling (TUNEL) and protein and mRNA levels of caspase-3, Bax and Bcl-2. Results show that co-application of ketamine and ethanol significantly increased immobility time in the forced swimming test, up-regulated TUNEL positive cells and both protein and mRNA expressions of caspase-3 and Bax, compared with the control group and ketamine and ethanol use alone groups in the PFC, but not in the HIP. Our study suggests that chronic co-administration of ketamine and ethanol results in depressive-like behavior and the caspase-dependent apoptosis in the PFC of adolescent rats' brains., (Copyright © 2019 Elsevier Inc. All rights reserved.)