基于动物学、临床医学跨界研究快速准确诊断1例不明蛇类咬伤的分析

目的 探讨动物学、临床医学跨界研究成果联合运用于快速准确诊断不明蛇类咬伤中的作用及效果.方法 通过回顾性分析1例不明蛇类咬伤患者的临床资料,从病史、动物学生活习性、咬痕鉴别、流行病学、临床表现、蛇类动物学分布6个方面进行剖析不明蛇类咬伤的诊断思路与方法.结果 该例蛇伤患者的病史特征以及诊断与鉴别诊断:(1)病史特征符合...     

The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.     

LOXL1‐AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR‐374b‐5p/MMP14 axis

At present, growing evidence indicates that long non‐coding RNAs (lncRNAs) participate in the progression of glioma. The function of LOXL1‐AS1 in vasculogenic mimicry (VM) in glioma remains unclear. First, the expressions of TIAR, the lncRNA LOXL1‐AS1, miR‐374b‐5p and MMP14 were examined by qRT‐PCR and Western blot in both, glioma tissues and glioma cell lines. Proliferation, migration, invasion and tube formation assays were conducted to evaluate the roles of TIAR, LOXL1‐AS1, miR‐374b‐5p and MMP14 in malignant cellular behaviours in glioma cells. A nude mouse xenograft model and dual staining for CD34 and PAS were used to assess whether VM was affected by TIAR, LOXL1‐AS1 or miR‐374b‐5p in vivo. In this study, low levels of TIAR and high levels of LOXL1‐AS1 were found in glioma cells and tissues. TIAR downregulated the expression of LOXL1‐AS1 by destabilizing it. LOXL1‐AS1 acted like a miRNA sponge towards miR‐374b‐5p so that downregulation of the former greatly inhibited cell proliferation, migration, invasion and VM. Additionally, miR‐374b‐5p overexpression repressed malignant biological behaviours and VM in glioma by modifying MMP14. In summary, we demonstrated that TIAR combined with LOXL1‐AS1 modulates VM in glioma via the miR‐374b‐5p/MMP14 axis, revealing novel targets for glioma therapy.     

Correlation between vaginal microbiota and different progression stages of cervical cancer

The process from high-risk human papillomavirus (HR-HPV) infection to cervical cancer is a continuous and long-term process, but the pathogenesis of the whole process is not completely clear. Here, 59 Chinese women were engaged in this study, and divided into five groups: normal healthy group, HR-HPV infections group, low-grade intraepithelial neoplasia (LSIL) group, high-SIL(HSIL) group, and cervical cancer group. With the occurrence of HR-HPV infection and the development of cervical lesions, the diversity of vaginal microbiota species was increased, and the relative abundance of Lactobacillus (L.), the dominant bacteria in maintaining vaginal microecological balance, was decreased gradually. In contrast, the abundance of Actinobacteria in the four disease groups was significantly higher than that in normal group. Furthermore L. iners may be related to the serious progression of cervical cancer. After analyzing the whole process, we found that Gardnerella(G.), Atopobium(A.) and Dialister(D.) have important effects on both persistent HR-HPV infection and the pathogenesis of cervical cancer. In addition, PICRUSt2 and KEGG results showed that the KEGG pathways enriched by the predicted genes of vaginal microbiota in cancer group included metabolic diseases, endocrine system and immune systems when compared with that in normal group. These findings may provide insights into the pathogenesis of cervical cancer, and help to improve the early detection and prevention of cervical precancerous lesions.     

Airway secretory cell fate conversion via YAP‐mTORC1‐dependent essential amino acid metabolism

Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular mechanisms governing these processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells, which subsequently lose their cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lung. This cell fate conversion is mediated via distinctive transitional cell states of damage‐associated transient progenitors (DATPs), recently shown to emerge during injury repair in mouse and human lungs. We further describe a YAP/TAZ signaling cascade to be integral for the fate conversion of secretory cells into AT1 fate, by modulating mTORC1/ATF4‐mediated amino acid metabolism in vivo. Importantly, we observed aberrant activation of the YAP/TAZ‐mTORC1‐ATF4 axis in the altered airway epithelium of bronchiolitis obliterans syndrome, including substantial emergence of DATPs and AT1 cells with severe pulmonary fibrosis. Genetic and pharmacologic inhibition of mTORC1 activity suppresses lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases.     

Improve survival prediction using principal components of gene expression data

The purpose of many microarray studies is to find the association between gene expression and sample characteristics such as treatment type or sample phenotype. There has been a surge of efforts developing different methods for delineating the association. Aside from the high dimensionality of microarray data, one well recognized challenge is the fact that genes could be complicatedly inter-related, thus making many statistical methods inappropriate to use directly on the expression data. Multivariate methods such as principal component analysis （PCA） and clustering are often used as a part of the effort to capture the gene correlation, and the derived components or clusters are used to describe the association between gene expression and sample phenotype. We propose a method for patient population dichotomization using maximally selected test statistics in combination with the PCA method, which shows favorable results. The proposed method is compared with a currently well-recognized method.     

PLA2R-IgG间接荧光定量免疫层析分析的构建与应用

目的 血清抗磷脂酶A2受体抗体IgG (PLA2R-IgG)水平是诊断和治疗特发性膜性肾病（IMN）的重要依据,而目前国内外常规检测手段主要是酶免法。为提升检测的便捷性,同时满足灵敏、宽量程分析需求,本研究构建了一种新的PLA2R-IgG检测技术。方法 采用包裹铕元素的微球示踪,对反应步骤进行选择,对微球制备液的p H、微球-抗体反应比例和反应时间优化,本文基于间接法构建了PLA2R-IgG的荧光定量免疫层析检测方法,并进行了初步临床评价。结果 本方法的灵敏度达0.7 RU/ml,标准曲线方程为y=0.771x-1.437,相关系数0.995,线性测量范围为0.7～1 500 RU/ml,回收率为86.27%～98.98%,平均批内变异系数为8.13%,交叉反应率均小于0.1%,试剂37℃储存10 d稳定。本方法与市售酶免试剂盒相关性为0.953,阴阳性判断一致,对IMN的检出率为76.9%。结论 采用两步法反应的PLA2R-IgG间接荧光定量免疫层析分析,快速、灵敏、准确,具有临床实用性。     

新疆准噶尔盆地玛湖凹陷玛页1井宾夕法尼亚亚系至乌拉尔统风城组孢粉地层学研究

提要准噶尔盆地西北缘玛湖凹陷风城组主要形成于碱湖环境,含有优质生烃母岩。对玛页1井风城组岩心样品的孢粉分析建立了Protohaploxypinus perfectus–Lunatisporites tersus (PT)孢粉组合。该组合包括20属29种孢粉化石。PT组合以双气囊具肋花粉占主导,蕨类孢子含量很低为特征;孢粉母体植物类群以裸子植物门种子蕨盾籽目为主,其次为松柏纲松柏目。该组合与准噶尔盆地南缘塔什库拉组上部至乌拉泊组的Crustaesporites–Protohaploxypinus–Hamiapollenites孢粉组合可以对比,均以双气囊具肋花粉为主要特征,又同时出现重要的属种Gardenasporites bilabiatus,Triangulisaccites boleensis和Hamiapollenites saccatus。孢粉地层学和同位素年代学资料表明,玛页1井风城组PT组合的时代很可能属于石炭纪宾夕法尼亚亚纪卡西莫夫期至二叠纪乌拉尔世阿瑟尔期,玛湖凹陷区整个风城组沉积时代晚于宾夕法尼亚亚纪巴什基尔期,其上部可能包含部分乌拉尔世阿瑟尔期沉积。风城组黑色页岩中...     

Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase

N-demethylases have been reported to remove the methyl groups on primary or secondary amines, which could further affect the properties and functions of biomacromolecules or chemical compounds; however, the substrate scope and the robustness of N-demethylases have not been systematically investigated. Here we report the recreation of natural evolution in key microdomains of the Thermomicrobium roseum sarcosine oxidase (TrSOX), an N-demethylase with marked stability (melting temperature over 100 °C) and enantioselectivity, for enhanced substrate scope and catalytic efficiency on -C-N- bonds. We obtained the structure of TrSOX by crystallization and X-ray diffraction (XRD) for the initial framework. The natural evolution in the nonconserved residues of key microdomains—including the catalytic loop, coenzyme pocket, substrate pocket, and entrance site—was then identified using ancestral sequence reconstruction (ASR), and the substitutions that accrued during natural evolution were recreated by site-directed mutagenesis. The single and double substitution variants catalyzed the N-demethylation of N-methyl-L-amino acids up to 1800- and 6000-fold faster than the wild type, respectively. Additionally, these single substitution variants catalyzed the terminal N-demethylation of non-amino-acid compounds and the oxidation of the main chain -C-N- bond to a -C=N- bond in the nitrogen-containing heterocycle. Notably, these variants retained the enantioselectivity and stability of the initial framework. We conclude that the variants of TrSOX are of great potential use in N-methyl enantiomer resolution, main-chain Schiff base synthesis, and alkaloid modification or degradation.