Thioredoxin 1 overexpression attenuated diabetes-induced endoplasmic reticulum stress in Müller cells via apoptosis signal-regulating kinase 1

As one of the common and serious chronic complications of diabetes mellitus (DM), the related mechanism of diabetic retinopathy (DR) has not been fully understood. Müller cell reactive gliosis is one of the early pathophysiological features of DR. Therefore, exploring the manner to reduce diabetes-induced Müller cell damage is essential to delay DR. Thioredoxin 1 (Trx1), one of the ubiquitous redox enzymes, plays a vital role in redox homeostasis via protein–protein interactions, including apoptosis signal-regulating kinase 1 (ASK1). Previous studies have shown that upregulation of Trx by some drugs can attenuate endoplasmic reticulum stress (ERS) in DR, but the related mechanism was unclear. In this study, we used DM mouse and high glucose (HG)-cultured human Müller cells as models to clarify the effect of Trx1 on ERS and the underlying mechanism. The data showed that the diabetes-induced Müller cell damage was increased significantly. Moreover, the expression of ERS and reactive gliosis was also upregulated in diabetes in vivo and in vitro. However, it was reversed after Trx1 overexpression. Besides, ERS-related protein expression, reactive gliosis, and apoptosis were decreased after transfection with ASK1 small-interfering RNA in stable Trx1 overexpression Müller cells after HG treatment. Taken together, Trx1 could protect Müller cells from diabetes-induced damage, and the underlying mechanism was related to inhibited ERS via ASK1.     

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 10⁶/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.     

Metabolomic study of the bone trabecula of osteonecrosis femoral head patients based on UPLC–MS/MS

The severity and/or progression of osteonecrosis of the femoral head (ONFH) are commonly assessed by radiography, nuclear magnetic resonance image which aren’t invariably correlated to severity of disease and may be disturbed by other factors. Consequently, exploring the novel biochemical signatures of ONFH may be beneficial for diagnosing and understanding this disease. In this work, a bone trabecula metabolomics was undertaken to determine the expression pattern of low molecular mass metabolites in patients of femoral head necrosis based on the ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS). Histological study showed that necrotic bone was characterized by necrosis, fibrosis and lacuna, but adjacent “normal” bone was pathologically normal. Principal component analysis in combination with orthogonal partial least-squares discrimination analysis was used to find out changed metabolites. MS/MS was used to speculate the corresponding molecule. Both osteonecrotic bone trabecula (ONBT) and adjacent “normal” bone trabecula (ANBT) showed higher levels of amino acids, such as proline, arginine, glutamine, dipeptides and lower levels of antioxidants. Most disrupted lipids, such as fatty acid esters, glycerophospholipids, sphingolipids, were found in osteonecrotic zone. The area under the receiver operating characteristic curve of combinational biomarkers (d-arginine, l-proline, l-carnitine, inosine) in ONBT and ANBT was 0.996 and 0.950, respectively. Our findings might provide a significant insight to understand the metabolic mechanism and diagnosis biomarkers of ONFH in the future.     

西南喀斯特地区两种草本对干湿交替和N添加的生长响应

喀斯特地区的"岩溶干旱"和频繁的变水环境成为喀斯特地区植被生长和分布的重要选择压力,是该地区植被恢复重建的主要障碍因子。N沉降也会对喀斯特地区的生态系统造成难以预测的影响。为了探究喀斯特地区草本植物对干湿交替和N添加的生长响应,以苍耳(Xanthium sibiricum)和三叶鬼针草(Bidens pilosa)为研究对象,通过盆栽水分受控实验,研究了5种不同水分处理[对照组(CK)、干旱组(D)、1周干湿交替处理组(DW-1)、2周干湿交替处理组(DW-2)和3周干湿交替处理组(DW-3)]与N添加(N+、N-)对两种草本植物生长和生物量的影响。结果表明,干旱胁迫抑制了植物生长和生物量的积累,株高、叶面积、总根长和根体积等生长指标和地上生物量均显著降低,根冠比增大。不同程度的干湿交替对植物的生长和生物量的积累均表现出一定程度的补偿效应,但这种补偿效应的大小随着干旱持续时间的延长而减弱。N添加对植物的生长和生物量积累有显著地促进作用,株高、根表面积、根体积和根生物量较对照组显著增加,但这种促进作用随着干旱历时的增加而减弱,可能与土壤水分状况有关。同时,N添加还影响着植物生物量的分配,在促进两种植物地上和地下生长的同时,还促进了植物根冠比的增加。     

杉木与伴生植物凋落物混合分解的相互作用研究

通过对杉木与9种伴生植物凋落物混合分解特征比较研究表明,8种植物对杉木凋落物的分解均有不同程度的促进作用,其中观音座莲对杉木凋落物分解的促进最大,而木荷对杉木凋落物分解的影响则表现出先有一定程度的促进而后又有微弱的抑制作用,促进大小表现出观音座莲＞杜茎山＞三龙爪＞狗脊＞苎麻＞丝栗栲＞闽粤栲＞芒萁。杉木 落物反过来对木荷和闽粤栲凋落物有一些抑制作用,而对丝栗栲则有一些促进作用,但这种相互作用未达到显著差异水平。说明杉木与某些伴生植物种类的凋落物在混合分解过程中存在着相互作用的现象,因此,合理保护和恢复林下植物对加快杉木人工林生态系统的养分循环和地力维护具有重要的意义。     

6种草本植物对干旱胁迫和CO2浓度升高交互作用的生长响应

以CO2浓度升高为主要标志的全球气候变化及由其引起的极端气候变化对陆地生态系统产生了重要的影响。利用步入式CO2生长室模拟研究了CO2浓度变化(400和700μL/L)和干旱胁迫(水分充足CK:100%FC(田间持水量);中度干旱MS:40%FC;重度干旱SS:20%FC)的交互作用对草本植物网果酸模(Rumex chalepensis)、野豌豆(Vicia sepium)、泥胡菜(Hemmistepta lyrata)、风轮菜(Clinopodium chinense)、藜(Chenopodium album)和玉米石(Sedum album)生长特性的影响。结果表明:CO2浓度升高总体上刺激了网果酸模、野豌豆、泥胡菜、风轮菜和藜这5种C3植物在任何水分条件下的生长,也刺激了玉米石在水分条件较好下的生长;干旱胁迫总体上抑制了所有6种植物的生长,但中度干旱胁迫有刺激CAM植物玉米石生长的趋势。CO2浓度升高能否缓解干旱的负面影响具有明显的种间差异:CO2浓度升高减缓了干旱胁迫对泥胡菜和风轮菜的负面影响,这种缓解作用在网果酸模和野豌豆中显著降低,对藜没有明显的促进作用,对干旱下的玉米石的生长却起到了抑制作用。CO2浓度升高总体上增加了根质量分数和干物质含量;干旱胁迫明显提高了6种草本植物的根生物量的分配比例,降低了干物质含量;但CO2浓度升高和干旱胁迫的交互作用可导致不同的物种产生不同的响应,说明植物能够通过调节生物量分配和植株本身的水分含量保持能力来适应CO2浓度和干旱胁迫的交互影响,这种调节能力取决于植物在碳的吸收和水分散失之间的平衡"trade-off"。研究结果有助于增进草本植物对未来气候变化的适应性理解,为评估和预测全球气候和水文变化对植物的生理生态影响提供理论依据。     

TGF-β1基因SNPs与长沙汉族人群脑卒中的相关性研究

目的:通过对长沙汉族人群TGFB1的多态分布规律的研究,从遗传流行病学的角度探讨TGFB1 SNPs(单核甘酸多态性)与长沙汉族人群脑卒中的关系。方法:应用PCR、RFLP及DNA直接测序等方法对研究人群进行-509C>T及+869T>C基因分型。研究对象包括:脑梗死(CI)患者186例,脑出血(CH)患者202例,正常对照人群160例。结果:脑梗死组(CI)和脑出血组(CH)分别与对照组比较,-509C>T和+869T>C基因型及等位基因频率分布无统计学差异(P>0.05),有脑梗死家族史的患者(FCI组)与对照组比较,-509 T等位基因携带者及+869C等位基因携带者频率较高(P<0.05),其中-509 T携带者脑梗死的患病风险为对照组的1.557倍,+869C携带者脑梗死的患病风险为对照组的1.45倍。结论:TGFB1-509C>T及+869T>C与有脑梗死家族史的长沙汉族人群脑梗死发病可能相关,但与有脑出血家族史的长沙汉族人群脑出血发病无关,-509T和+869C等位基因可能是有脑梗死家族史的长沙汉族人群脑梗死发病的危险因子。