Upregulation of LRRC8A by m5C modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer

Cervical cancer (CC) is one of the most common gynecological malignancies with poor prognosis for advanced CC patients. LRRC8A is a volume-regulated anion channel protein involved in cellular homeostasis, but its role in CC remains largely unknown. In this study, we found that LRRC8A is elevated in CC and associated with poor prognosis. LRRC8A maintains cell survivals under the hypotonic condition, and promotes tumorigenesis through apoptosis suppression in vitro and in vivo. Notably, LRRC8A is upregulated by NSUN2-mediated m⁵C modification. m⁵C modified-LRRC8A mRNA is bound by the RNA binding protein YBX1 followed by the increased RNA stability. Moreover, loss of NSUN2 suppresses the proliferation and metastasis of CC cells, and NSUN2 expression is positively correlated with LRRC8A expression in CC. Altogether, our study demonstrates that the NSUN2-m⁵C-LRRC8A axis is crucial and would be a potential therapeutic target for CC.     

来源于铜绿假单胞杆菌(Pseudomonas aeruginosa)所产蛋白酶PT121克隆表达及其在小肽合成上的应用

【目的】基于前期筛选到的P.aeruginosa PT121所产有机溶剂耐受性蛋白酶,本研究对该蛋白酶进行克隆表达,研究了重组蛋白的酶学性质及小肽合成上的应用。【方法】参考文献中报道的相似蛋白酶pseudolysin设计引物从菌株PT121基因组中克隆到耐有机溶剂蛋白酶PT121基因las B。构建诱导表达重组质粒p ET22b-las B,于大肠杆菌中进行表达。考察蛋白酶PT121酶学性质及小肽合成上的应用。【结果】序列分析表明las B基因编码信号肽、前肽及成熟肽3个部分,成熟肽部分含有301个氨基酸,分子量约33 k Da,属于金属蛋白酶M4家族。通过破碎条件优化,一步法制备得到较为纯净的重组蛋白酶PT121,其比活力达7700 U/mg,该酶呈现了较高的热稳定性,p H稳定性及溶剂耐受性,与野生菌P.aeruginosa PT121所产蛋白酶性质一致。在50%DMSO体系中高效催化合成了多种小肽,其中阿斯巴甜前体(Cbz-Asp-Phe-NH2)产率高达91%。【结论】蛋白酶PT121基因在大肠杆菌中克隆表达为进一步研究相关催化机理及分子改造奠定了基础。     

脓毒性心肌功能障碍

脓毒症是由感染引起的全身炎症反应综合征,证实有感染灶存在或有高度可疑的感染灶。脓毒症是ICU内重症患者的主要死亡原因,且发病率随着年龄的增长而逐渐增加。近十年来,虽然政府在救治脓毒症患者中投入了巨大的资金和技术支持,但源于脓毒症或脓毒性休克患者的病死率仍高达30%~60%。心血管系统在脓毒症与脓毒性休克的病理生理学中扮演着重要着色。过去的四五十年,开展了很多脓毒性心肌功能障碍方面的研究,也积累了不少循证医学证据。然而,心脏只是心血管系统的一部分。诸如脓毒症患者机体血流动力学的变化系脓毒症对心脏的直接效应,还是脓毒症引起心脏前、后负荷及神经体液因素的变化,继而引起心脏继发改变的研究,至今仍在继续。本文概述了近年来脓毒性心肌功能障碍的研究进展,使读者更全面地了解脓毒性心肌功能障碍的病理生理学改变,合理有效地指导脓毒症和脓毒性休克患者的临床救治。     

中华山蝠翼的形态学发育模式

为了揭示中华山蝠翼的形态学发育模式,2012-2014年, 通过对50只中华山蝠幼蝠进行人工饲养实验观察及测量,辅以野外标志重捕,研究中华山蝠翼的生长。结果显示：中华山蝠翼外形各量度值先呈直线增长,后增长速度逐渐减慢。各指标增长速度减慢的日龄各不相同,臂膜长在25日龄生长速度逐渐减慢;翼展、翼面积、臂膜面积在30日龄增长速度减慢;掌膜长及掌膜面积则在40日龄增长速度减慢。臂膜长发育最快,试飞前 (28日龄) 已达到成体臂膜长的80.9%。翼载在幼蝠生后14日龄内呈直线增长,然后开始直线下降,到试飞期 (35日龄左右),翼载值降到最低,是成体翼载的80.0%,此后呈极缓慢增长趋势。中华山蝠翼的生长主要集中在试飞前。试飞后,则通过减缓体重的增长速度甚至减轻体重,保持翼面积尤其是掌膜面积的增长速度,从而降低翼载,以便更快地适应飞行生活。Logistic, Von Bertalanffy和Gompertz 3种非线性曲线中,Gompertz模型对翼展拟合度最佳,Gompertz和Von Bertalanffy模型对翼面积拟合度优于Logistic曲线。     

Highly sensitive and selective uric acid biosensor based on a three-dimensional graphene foam/indium tin oxide glass electrode

A three-dimensional (3D) continuous and interconnected network graphene foam (GF) was synthesized by chemical vapor deposition using nickel foam as a template. The morphologies of the GF were observed by scanning electron microscopy. X-ray diffraction and Raman spectroscopy were used to investigate the structure of GF. The graphene with few layers and defect free was closely coated on the backbone of the 3D nickel foam. After etching nickel, the GF was transferred onto indium tin oxide (ITO) glass, which acted as an electrode to detect uric acid using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The GF/ITO electrode showed a high sensitivity for the detection of uric acid: approximately 9.44 mA mM⁻¹ in the range of 25 nM–0.1 μM and 1.85 mA mM⁻¹ in the range of 0.1–60 μM. The limit of detection of GF/ITO electrode for uric acid is 3 nM. The GF/ITO electrode also showed a high selectivity for the detection of uric acid in the presence of ascorbic acid. This electrode will have a wide range of potential application prospects in electrochemical detection.     

PCR-DGGE技术解析东北稻田蓝藻群落结构

[目的]明确东北稻田生态系统蓝藻群落结构组成变化及主要驱动因子。[方法]采用蓝藻特异性引物GC-Cya-b-F371和Cya-R783对采自东北不同土壤类型稻田土壤及田面水提取的DNA进行PCR扩增,采用DGGE电泳和条带测序技术解析稻田蓝藻群落结构。[结果]多样性指数表明,土壤中蓝藻群落结构比田面水体丰富。图谱冗余分析(RDA)显示,稻田土壤中蓝藻群落结构具有明显的地域差异,土壤碳氮比值是驱动土壤蓝藻分布的主要环境因素;而田面水体蓝藻群落结构地域差异不明显,p H值是驱动水体蓝藻分布的主要环境因素。DGGE条带测序发现,稻田蓝藻群落结构组成以丝状颤藻亚纲蓝藻(Oscillatoriophycideae)为主,一些条带基因序列与已知蓝藻相似度低于97%。[结论]东北稻田生态系统蓝藻群落结构复杂多样,生存着一些未知的蓝藻种群。     

Intrinsic Functional Plasticity of the Sensorimotor Network in Relapsing-Remitting Multiple Sclerosis: Evidence from a Centrality Analysis

Background and Purpose

Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS). However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN) and to assess network integrity and connectedness.

Methods

Thirty-four patients with clinically definite RRMS and well-matched healthy controls participated in the study. Twenty-three patients in the remitting phase underwent one resting-state functional MRI, and 11 patients in the relapsing-remitting phase underwent two different MRIs. We measured voxel-wise centrality metrics to determine direct (degree centrality, DC) and global (eigenvector centrality, EC) functional relationships across the entire SMN.

Results

In the relapsing phase, DC was significantly decreased in the bilateral primary motor and somatosensory cortex (M1/S1), left dorsal premotor (PMd), and operculum-integrated regions. However, DC was increased in the peripheral SMN areas. The decrease in DC in the bilateral M1/S1 was associated with the expanded disability status scale (EDSS) and total white matter lesion loads (TWMLLs), suggesting that this adaptive response is related to the extent of brain damage in the rapid-onset attack stage. During the remission process, these alterations in centrality were restored in the bilateral M1/S1 and peripheral SMN areas. In the remitting phase, DC was reduced in the premotor, supplementary motor, and operculum-integrated regions, reflecting an adaptive response due to brain atrophy. However, DC was enhanced in the right M1 and left parietal-integrated regions, indicating chronic reorganization. In both the relapsing and remitting phases, the changes in EC and DC were similar.

Conclusions

The alterations in centrality within the SMN indicate rapid plasticity and chronic reorganization with a biased impairment of specific functional areas in RRMS patients.     

New strategy for in vitro activation of primordial follicles with mTOR and PI3K stimulators

It had been known for decades that primordial follicles in mammalian ovaries are assembled with definite numbers and represent the ovarian reserve throughout the reproductive life. Intra-oocyte PI3K/mTOR pathways have been indicated to play a central role on the activation of primordial follicles. Genetic modified mouse models with chronic activation of PI3K/mTOR signals in primordial oocytes showed premature activation of all primordial follicles and eventually their exhaustion. On the other hand, this may suggest that, unlike chronic activation of PI3K/mTOR, its acute activation in infertility would activate primordial follicles, permitting fertility during the treatment. Previously, PI3K stimulators were reported as a temporary measure to accelerate primordial follicle activation and follicular development in both mouse and human, and were applied in the treatment of infertility in premature ovarian failure (POF) patients. To address whether mTOR stimulators could play similar role in the process, we transiently treated neonatal and aged mouse ovaries with mTOR stimulators-phosphatidic acid (PA) and propranolol. Our results demonstrated the stimulators increased activation of primordial follicles and the production of progeny. Human ovarian cortex cubes were also treated with mTOR or/and PI3K stimulators in vitro. When they were used separately, both of them showed similar promotive effects on primordial follicles. Surprisingly, after joint-treatment with the 2 kinds of stimulators together, synergistic effects on follicular development were observed. Based on increased efficiency of follicular activation in humans, here we propose in vitro transient treatment with mTOR and PI3K stimulators as an optimized protocol for the application in different clinical conditions with limited follicle reserve.