Novel mutations in ADAMTS13 CUB domains cause abnormal pre-mRNA splicing and defective secretion of ADAMTS13

Hereditary thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive thrombosis disorder, caused by loss-of-function mutations in ADAMTS13. Mutations in the CUB domains of ADAMTS13 are rare, and the exact mechanisms through which these mutations result in the development of TTP have not yet been fully elucidated. In this study, we identified two novel mutations in the CUB domains in a TTP family with an acceptor splice-site mutation (c.3569−1, G>A, intron 25) and a point missense mutation (c.3923, G>A, exon 28), resulting in a glycine to aspartic acid substitution (p.G1308D). In vitro splicing analysis revealed that the intronic mutation resulted in abnormal pre-mRNA splicing, and an in vitro expression assay revealed that the missense mutation significantly impaired ADAMTS13 secretion. Although both the patient and her brother displayed significantly reduced ADAMTS13 activity and increased levels of ultra-large VWF (ULVWF) multimers in plasma, only the female developed acute episodes of TTP. Our findings indicate the importance of the CUB domains for the protein stability and extracellular secretion of ADAMTS13.     

MicroRNA‐29b‐3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway

Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR‐29b‐3p as a guarder that suppressed migration and invasion of OSCC cells and was down‐regulated in the most invasive cells. Besides that, the invasion suppression role of miR‐29b‐3p was achieved through the IL32/AKT pathway. Thus, miR‐29b‐3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.     

Vacancy in Ultrathin 2D Nanomaterials toward Sustainable Energy Application

The unique physicochemical properties of (2D) nanomaterials make them well‐suited for use in sustainable energy applications. Many of these materials can be further improved with vacancy engineering. This review details recent progress in the vacancy engineering of ultrathin 2D nanomaterials. For clarity, it mainly focuses on various ultrathin 2D materials in three categories: X_a&X_aY_b‐, M_aX_b‐, or M_aX_bY_c‐structured materials. Recently developed vacancies in different types of ultrathin 2D materials, as well as their preparation and characterization, are described. Emphasis is placed on the potential electrochemical energy storage and conversion applications of these materials. This review considers the relationship between vacancy properties and material categories of various ultrathin 2D materials in terms of application requirements, preparation, and characterization techniques. The challenges and future outlook of this promising field are summarized.     

Half‐Heusler Thermoelectric Module with High Conversion Efficiency and High Power Density

Half‐Heusler (HH) compounds have shown great potential in waste heat recovery. Among them, p‐type NbFeSb and n‐type ZrNiSn based alloys have exhibited the best thermoelectric (TE) performance. However, TE devices based on NbFeSb‐based HH compounds are rarely studied. In this work, bulk volumes of p‐type (Nb_0.8Ta_0.2)_0.8Ti_0.2FeSb and n‐type Hf_0.5Zr_0.5NiSn_0.98Sb_0.02 compounds are successfully prepared with good phase purity, compositional homogeneity, and matchable TE performance. The peak zTs are higher than 1.0 at 973 K for Hf_0.5Zr_0.5NiSn_0.98Sb_0.02 and at 1200 K for (Nb_0.8Ta_0.2)_0.8Ti_0.2FeSb. Based on an optimal design by a full‐parameters 3D finite element model, a single stage TE module with 8 n‐p HH couples is assembled. A high conversion efficiency of 8.3% and high power density of 2.11 W cm^?2 are obtained when hot and cold side temperatures are 997 and 342 K, respectively. Compared to the previous TE module assembled by the same materials, the conversion efficiency is enhanced by 33%, while the power density is almost the same. Given the excellent mechanical robustness and thermal stability, matchable thermal expansion coefficient and TE properties of NbFeSb and ZrNiSn based HH alloys, this work demonstrates their great promise for power generation with both high conversion efficiency and high power density.     

Direct Recycling of Spent NCM Cathodes through Ionothermal Lithiation

Ionic liquids (ILs) are a family of nonconventional molten salts that offer many advantages, such as negligible vapor pressures, negligible flammability, wide liquidus ranges, good thermal stability, and much synthesis flexibility. The unique solvation environment of these ILs provides new reaction or flux media for controlling formation of solid‐state materials with a minimum perturbation of morphologies. A successful lithiation via ionothermal synthesis using a cost‐effective Li halide as Li source and recyclable ILs as solvents is reported here for the direct recycling of LiNi_1/3Co_1/3Mn_1/3O₂ (NCM 111) cathodes. In addition, the ionic liquids can be readily recycled and reused after ionothermal lithiation. The lithiation of spent cathodes can enable the direct recycling of spent cathode materials in lithium‐ion batteries.     

小黑杨PsnHB13基因在烟草中的遗传转化与功能分析

克隆小黑杨HD-ZIP家族基因PsnHB13,对该基因进行生物信息学分析、过表达载体构建、烟草的遗传转化。结果表明小黑杨PsnHB13基因cDNA全长870 bp,编码289个氨基酸。成功构建植物过表达载体pROKⅡ-PsnHB13,并通过农杆菌介导的叶盘法将外源基因转入野生型烟草。检测结果显示PsnHB13已成功整合入烟草基因组中,并在mRNA水平表达。通过观察转基因烟草的生长,发现过表达PsnHB13基因的烟草与野生型相比出现叶面积变小、叶型变长,根系生长缓慢,花朵变小等明显表型。说明PsnHB13基因主要对烟草叶片、根系及花的生长发育起到负调控作用。本文为研究PsnHB13基因对杨树生长发育的影响提供理论基础。     

播散型组织胞浆菌病研究进展

组织胞浆菌病是由组织胞浆菌引起的深部真菌疾病。播散型组织胞浆菌病为所有临床分型中最为凶险的类型,其特点为起病急、发展快、死亡率高,诊断及治疗也颇为棘手。该病既往被认为是一种地方流行性疾病,多见于美国中西部等西半球地区,我国少见且多为输入性病例。但现阶段我国本土病例也屡有报道,故本文在复习相关文献基础上总结了播散型组织胞浆菌病的流行病学现状、易感人群、临床表现、诊断方法及治疗进展,以飨读者。     

阻断趋化因子CXCL10对脑缺血再灌注损伤及神经炎症的影响

目的:探讨趋化因子CXCL10在脑缺血再灌注损伤中对神经炎症的影响。方法:(1)线栓法建立脑缺血再灌注损伤大鼠模型,TTC染色检测梗死面积,Western blot检测CXCL10的表达;(2)建立小鼠神经瘤母细胞N2a氧糖剥夺/复氧(oxygen-glucose deprivation/reoxygenation,OGD/R)模型,通过CXCR3拮抗剂-NBI 74330阻断趋化因子CXCL10表达,Western blot检测CXCL10和CXCR3蛋白的表达;Real-time PCR检测CXCL10、CXCR3以及神经炎症因子TNF-α、IL-1β、IL-2 m RNA的表达。结果:(1)脑缺血再灌注(cerebral ischemia reperfusion injury,CIRI)模型大鼠脑梗死侧CXCR10的表达量显著高于其对侧和假手术组(P<0.05);(2)阻断CXCL10使得小鼠神经瘤母细胞N2a中CXCL10、CXCR3以及炎症因子TNF-α、IL-1β、IL-2的表达量均显著降低(P<0.05);(3)阻断CXCL10使得小鼠神经瘤母细胞细胞凋亡率降低(P<0.05)。结论:抑制CXCL10降低了氧糖剥夺模型细胞炎症因子的表达,表明阻断CXCL10可能通过减轻神经炎症在脑缺血再灌注损伤中发挥保护作用。     

合并慢性气道疾病的ARDS临床特征及预后影响因素研究

目的:探讨急性呼吸窘迫综合征(ARDS)合并慢性气道疾病患者的临床特征及影响预后的因素。方法:167例ARDS患者根据并发症发生情况分为对照组(单纯性ARDS组,A组,n=39)及观察组(ARDS合并慢性气道疾,B组,n=49,C组,n=41,D组,n=38),比较各组患者一般情况、临床特征、生化指标、治疗方式及预后状况,通过logistic回归分析ARDS合并慢性气道疾病患者预后的影响因素。结果:观察组(B、C、D组)年龄、中性粒细胞、IL-6、IL-8、TNF-α、白蛋白、pro-BNP、乳酸、氧合指数、住院时间、住院费用与对照组(A组)比较差异有统计学意义,P0.05;128例ARDS合并慢性气道疾病患者中死亡76例,好转52例,病死率59.38%;单因素分析结果显示,观察组(B、C、D组)患者中临床结局好转患者与死亡患者比较,白细胞、淋巴细胞、CRP、TNF-α、IL-8、降钙素、肌酐、pro-BNP、氧合指数、住院费用、机械通气时间、抗生素数量差异有统计学意义,P0.05;通过多因素logistic回归分析发现肌酐是影响ARDS合并慢性气道疾病的潜在危险因素,氧合指数为保护因素,P0.05。结论:ARDS合并慢性气道疾病的能量代谢紊乱程度可能较单纯ARDS加重,且两者炎性特征不同。肌酐、氧合指数是影响ARDS合并慢性气道疾病的重要影响因素。     

尺神经原位松解术与尺神经皮下前置术治疗肘管综合征近期疗效比较的回顾性研究

目的:比较尺神经原位松解术与尺神经皮下前置术治疗肘管综合征(CuTS)近期疗效。方法:本研究为回顾性研究,选取2016年7月～2017年7月期间我院二部收治的60例CuTS患者,根据手术方式的不同分为A组(n=32,尺神经原位松解术)和B组(n=28,尺神经皮下前置术),比较两组患者优良率、并发症、围术期指标、感觉运动功能(肌力、小指指端两点辨别觉、神经传导速度)以及DASH上肢功能障碍(DASH)评分。结果:B组术后12个月的优良率为92.86%(26/28),高于A组的68.75%(22/32)(P0.05)。两组术后并发症总发生率比较差异无统计学意义(P0.05)。两组术后12个月肌力、神经传导速度升高,且B组高于A组(P0.05),两组术后12个月小指指端两点辨别觉降低,且B组低于A组(P0.05)。两组术后3个月、术后6个月、术后12个月DASH评分呈下降趋势,且B组低于A组(P0.05)。B组手术切口长度、手术时间长于A组(P0.05),两组术后住院时间比较差异无统计学意义(P0.05)。结论:与尺神经原位松解术相比,尺神经皮下前置术治疗CuTS患者,虽然手术切口长度、手术时间相对较长,但其优良率更高,同时可有效恢复患者感觉运动功能及减轻其上肢功能障碍,且不增加并发症发生率,具有一定的临床应用价值。