The Genomic Evolution and the Transmission Dynamics of H6N2 Avian Influenza A Viruses in Southern China

In China, the broad prevalence of H6 subtype influenza viruses, increasingly detected in aquatic birds, promotes their exchange materials with other highly pathogenic human-infecting H5N1, H5N6, and H7N9 influenza viruses. Strikingly, some H6 subtype viruses can infect pigs, dogs, and humans, posing risks to public health. In this study, 9 H6N2 viruses recovered from waterfowl species in the Guangdong province of China in 2018 were isolated and sequenced. Phylogenetic analysis revealed that the genome sequences of these H6N2 viruses belonged to Group I, except for the NP gene in Group III. Coalescent analyses demonstrated that the reassortment of NA and NS genes have occurred in two independent clusters, suggesting H6 subtype viruses had been undergoing a complex reassortant. To examine the evolutionary dynamics and the dissemination of the H6 subtype viruses, a Bayesian stochastic search variable selection was performed for results showing higher viral migration rates between closer provinces, including Guangdong, Jiangxi, Guangxi, and Fujian. Notably, the transmission routes of the H6 subtype viruses were concentrated in Jiangxi Province, the most frequent location for input and output transmission and a region containing Poyang Lake, a well-known wintering site for migration birds. We also found that the aquatic birds, especially ducks, were the most common input source of the viral transmission. In addition, we also found that eight positively selected amino acid sites were identified in HA protein. Given their continuous dissemination and the broad prevalence of the H6 subtype influenza viruses, continued surveillance is warranted in the future.     

Insight into the Epidemiology and Evolutionary History of Novel Goose Astrovirus-Associated Gout in Goslings in Southern China

A novel gout disease, characterized by visceral urate deposition with high-mortality, with outbreaks in goslings in China since 2016 was caused by a novel goose astrovirus (GoAstV) and resulted in serious economic loss. However, the epidemiology and variation of the GoAstV in goslings in southern China and its evolutionary history as well as the classification of the GoAstV are unclear. In the present study, systematic molecular epidemiology, and phylogenetic analyses of the GoAstV were conducted to address these issues. Our results showed that the GoAstV is widespread in goslings in southern China, and the genomes of six GoAstV strains were obtained. Two amino acid mutations (Y36H and E456D) were identified in capsid proteins in this study, which is the dominant antigen for the GoAstV. In addition, the GoAstV could be divided into two distinct clades, GoAstV-1 and GoAstV-2, and GoAstV-2 is responsible for gout outbreaks in goslings and could be classified into Avastrovirus 3 (AAstV-3), while GoAstV-1 belongs to Avastrovirus 1 (AAstV-1). Moreover, the emergence of GoAstV-2 in geese was estimated to have occurred in January 2010, approximately 12 years ago, while GoAstV-1 emerged earlier than GoAstV-2 and was estimated to have emerged in April 1985 based on Bayesian analysis. The mean evolutionary rate for the GoAstV was also calculated to be approximately 1.42 × 10⁻³ nucleotide substitutions per site per year. In conclusion, this study provides insight into the epidemiology of the GoAstV in goslings in southern China and is helpful for understanding the origin and evolutionary history as well as the classification of the GoAstV in geese.     

Numerical Simulation and Experimental Validation of Squeeze Casting of AlSi9Mg Aluminum Alloy Component with a Large Size

The squeeze casting process for an AlSi9Mg aluminum alloy flywheel housing component was numerically simulated using the ProCAST software, and orthogonal simulation tests were designed according to the L16 (4) ⁵ orthogonal test table to investigate the alloy melt flow rule under four factors and four levels each of the pouring temperature, mold temperature, pressure holding time and specific pressure, as well as the distributions of the temperature fields, stress fields and defects. The results showed that the flywheel housing castings in all 16 test groups were fully filled, and the thinner regions solidified more quickly than the thicker regions. Hot spots were predicted at the mounting ports and the convex platform, which could be relieved by adding a local loading device. Due to the different constraints on the cylinder surface and the lower end surface, the solidification was inconsistent, the equivalent stress at the corner junction was larger, and the castings with longer pressure holding time and lower mold temperature had larger average equivalent stress. Shrinkage cavities were mainly predicted at mounting ports, the cylindrical convex platform, the peripheral overflow groove and the corner junctions, and there was also a small defect region at the edge of the upper end face in some test groups.     

心律平联合ACEI或ARB对高血压室性心律失常患者QT离散度的影响

目的探讨心律平联合血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(ARB)对伴有左室肥厚的高血压室性心律失常患者QT离散度(QT interval disperson,QTd)的影响。方法检测60例伴有左室肥厚的高血压室性心律失常患者应用心律平和ACEI或ARB前后的QTd,并与60例健康对照者进行比较。结果病例组用药前与正常对照组相比,QTd有明显延长(P<0.05)。用药1个月后,病例组QTd较用药前略有缩短,但无统计学意义(P>0.05);用药3个月后,QTd较用药前仍有缩短与用药1个月时相似(P>0.05);用药6个月后,QTd较用药前有较明显缩短(P<0.05)。结论心律平联合ACEI或ARB应用于高血压伴左室肥厚及室性心律失常的患者时QTd无延长,是安全的用药方案。     

不同给药途径时抗核抗体独特型多肽对狼疮样肾炎小鼠作用的探讨

目的应用抗核抗体独特型多肽免疫治疗狼疮肾炎小鼠,观察其对狼疮肾炎模型小鼠肾脏的保护作用。方法将35只雌性GVHD狼疮样肾炎小鼠(C57BL/10×DBA/2)F1分为3组,肾炎模型对照组(10只),口服多肽实验组(10只),皮下注射多肽实验组(15只)。3组小鼠均于24周龄处死,观察3组小鼠体质量、尿蛋白、肾脏组织学及血清IL-6水平的变化。结果在给予多肽12周时,皮下注射组和口服多肽组小鼠肾脏损害较对照组明显减轻;血清IL-6水平也较对照组明显降低。在给予多肽10周时,皮下注射组小鼠体质量明显高于对照组小鼠,12周时口服组体质量也明显高于对照组。给予多肽4周时,皮下注射组小鼠尿蛋白明显少于对照组,8周时口服组尿蛋白也明显少于对照组。结论口服独特型多肽对GVHD狼疮样肾炎小鼠肾脏同样有保护作用。     

常见革兰阳性细菌鉴定与耐药检测基因芯片的临床应用

目的利用基因芯片技术进行常见革兰阳性细菌的细菌鉴定和耐药性检测。方法用生理生化鉴定和药敏纸片法确定445份革兰阳性细菌菌株的细菌种类和耐药性,盲法进行革兰阳性细菌鉴定与耐药检测基因芯片的检测,用SPSS 10.0 for Windows软件统计分析。结果与临床常规方法相比,耐药检测基因芯片鉴定指标的灵敏度均>96%,特异度均>98%;耐药检测指标的灵敏度均>94%,特异度均>90%。χ2检验结果P值均>0.05,基因芯片检测结果与临床常用方法检测结果差异无统计学意义。Kappa值均>0.75,2种方法一致性较好。结论基因芯片技术对细菌鉴定和耐药检测有一定的临床应用价值。     

The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice

Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS.Objectives: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.Methods: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms.Results: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice.Conclusions: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281     

Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension

BackgroundAberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.MethodsFresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E₂) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.ResultsMany circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E₂ strongly regulated it. E₂ decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E₂ reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E₂ and miR‐21‐5p antagonist.ConclusionsmiR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E₂ on MCT‐PH through ERβ.     

Preparation and characterization of pure phase CdMnTe nanopowders by a hydrothermal route

In this paper, CdMnTe nanopowders with uniform shapes were prepared through a facile hydrothermal route using 3-mercaptopropionic acid (MPA) as the stabilizer and modifier. The effects of different experimental conditions including Cd-to-MPA ratio, pH value and reaction temperature on the phase composition and formation mechanism of as-prepared nanopowders were studied. XRD results indicated as-prepared CdMnTe nanopowders were pure phase and had cubic sphalerite structure with high crystallinity. SEM and Rietveld refinement clearly showed that the powders were about 10–100 nm in size. In PL measurement, there was a strong luminescence peak in the infrared region 1.717–1.826 eV. Compared with the CdMnTe single crystal, a blue shift of about 0.109 eV indicated a wider band gap. In UV-vis spectra, the absorption peak of the sample blue shifted with the decrease of crystal size, which indicated an obvious quantum confinement effect (QCE) in nanopowders. The optimal conditions for the preparation of CdMnTe nanopowders are 180 °C for 24 h with the molar ratio 1 : 1 of Cd : MPA at pH 13. In particular, the growth kinetics and possible formation mechanism of the nanopowders were proposed.

CdMnTe high-quality and pure phase nanopowders, with diameters of 20 nm to 100 nm, were synthesized by a hydrothermal route using mercapto propionic acid as the stabilizer. A CdMnTe single crystal was produced by melting method and flash sintering using CdMnTe nanopowder.     

局部晚期不可手术食管癌同步放化疗联合尼妥珠单抗的初步临床分析

目的:探讨局部晚期食管癌同步放化疗联合尼妥珠单抗治疗的不良反应及疗效。方法:回顾性分析北京大学肿瘤医院2015—2020年间使用同步放化疗联合尼妥珠单抗治疗的30例患者资料,采用 Kaplan- Meier法生存分析。 结果:中位随访时间22.5个月,总客观有效率为93%。1、2、3年...