Gentiopicroside promotes the osteogenesis of bone mesenchymal stem cells by modulation of β-catenin-BMP2 signalling pathway

Osteoporosis is characterized by increased bone fragility, and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN), a class of natural compounds with numerous biological activities such as anti-resorptive properties and protective effects against bone loss. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy. In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, whereas in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months. Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and up-regulated the osteogenic factors (Runx2, OSX, OCN, OPN and BMP2). In vivo, GEN promoted the expression of Runx2, OCN and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/β-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/β-catenin inhibitor DKK1. Silencing the β-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only β-catenin was silenced, although the knockout of BMP2 did not affect β-catenin expression induced by GEN. Therefore, GEN promotes BMSC osteogenesis by regulating β-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.     

The History and Advances of Reversible Terminators Used in New Generations of Sequencing Technology

DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the "REAP" method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application.     

上升流和水团对浙江中部近海浮游动物生态类群分布的影响

依据2010年4月、7月和11月对浙江中部近海上升流海域进行的海洋调查资料,运用定量、定性方法,探讨了上升流对该海域浮游动物生态类群分布的影响.结果表明:3个季节共鉴定浮游动物64种,桡足类占主要优势,包括5个生态类群,分别是暖温带近海种、暖温带外海种、亚热带近海种、亚热带外海种和热带大洋种.在种类数组成上,春季以暖温带近海种为主,夏季则是亚热带近海种和亚热带外海种居多,秋季也是亚热带种居多,其中夏季暖温带种种类数要高于春季和秋季,这一现象与同时期东黄海沿海有所不同,主要是由于上升流将一些在海洋底部度夏的暖温种带至海洋表面造成的.此外,3个季节生态类群都是以近海种为主,表明沿岸流是影响这一海域的最主要的水团.在丰度组成上,4月暖温带近海种占总丰度的98.79％,7月暖温带近海种也是组成丰度的重要部分,10月则是亚热带近海种丰度最高.丰度组成所反映的规律与种类数组成规律一致.上升流的存在导致夏季近海暖温带种大量出现,是影响这一海域浮游动物生态类群组成的重要因素;受长江径流和椒江径流的影响,近海种成为主要生态类群,是这一海域浮游动物的一个重要的生态特征.     

Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II

Crigler–Najjar Syndrome type II (CNS-II) is an autosomal recessive hereditary condition of unconjugated hyperbilirubinemia without hemolysis, with bilirubin levels ranging from 102.6 μmol/L to 342 μmol/L. CNS-II is caused by a deficiency of UDP-glucuronyl transferase (UGT), which is encoded by the UDP-glucuronyl transferase 1A1 gene (UGT1A1). In East Asian populations, the compound homozygous UGT1A1 G71R and Y486D variants are frequently observed in cases with bilirubin levels exceeding 200 μmol/L. In this study, we investigated the spectrum of UGT1A1 variations in Chinese CNS-II patients. We sequenced the enhancer, promoter, and coding regions of UGT1A1 in 11 unrelated Chinese CNS-II patients and 80 healthy controls. Nine of these patients carried variations that are here reported for the first time in CNS-II patients, although they have been previously reported for other types of hereditary unconjugated hyperbilirubinemia. These individual variations have less influence on UGT activity than do the compound homozygous variation (combination of homozygous G71R variant and Y486D variant). Therefore, we propose that the spectrum of UGT1A1 variations in CNS-II differs according to the bilirubin levels.     

ACE2 and FZD1 are prognosis markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of gallbladder

The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan–Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1^?ACE2⁺ expression was significantly longer than that in patients with FZD1⁺ACE2^? or FZD1⁺ACE2⁺ (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer.     

用SARS冠状病毒全基因组芯片杂交方法分析SARS-CoV

为从临床样品中检测和分析SARSCoV病毒打基础,并为分析SARSCoV病毒的复制和转录等机理提供一种有效方法。以SARS冠状病毒TOR2株序列作为标准设计和制备一种覆盖SARS冠状病毒全基因组的寡聚核苷酸芯片,探针长度为70nt,每相邻的探针序列重复25nt,共660条。用该芯片分析了细胞培养的SARSCoV病毒总RNA、7个SARSCoV病毒的基因克隆片段。对RNA样品用随机引物进行反转录PCR获得cDNA。对DNA用随机引物扩增和dUTPcy3标记。结果用这种芯片杂交检测SARSCoV病毒RNA可见阳性信号呈全基因组分布,并且有多处连续的阳性信号点;用正常人的白细胞RNA为对照,杂交未出现明显阳性信号。检测7个SARSCoV病毒基因克隆片段,在该片段相应的探针区段出现连续阳性信号点。这种方法可有效地检测和分析样品中SARS冠状病毒全基因组的信息。     

基于湿度分布特征的小尺度土壤碳通量空间采样策略

由于土壤碳通量的空间异质性很强,传统的随机抽样方法无法对区域土壤碳通量进行准确估算,而多点采样需耗费大量的人力及设备成本,因此确定适当的采样点数量及分布策略对于区域土壤碳通量的测算非常重要。提出一种基于湿度空间分布特征的小尺度土壤碳通量空间采样策略:首先利用无线传感网密集测量区域的土壤湿度,根据湿度数据的空间分布特征划分监测区域,通过Hammond Mc Cullagh方程计算各子区域内的最优采样点数量,最终确定整个监测区域的空间采样点部署策略。提出的方法考虑了各子区域间土壤碳通量空间分布的差异,使得采样点的部署位置与土壤碳通量的分布具有较好的相关性。研究结果证明:土壤碳通量部署策略能够获得比均匀部署策略、随机部署策略更高的区域土壤碳通量估算准确度。     

Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the N-protecting group

This article describes the synthesis and biological evaluation of a group of N-protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to contribute to caspase-3 inhibiting activity, and compounds with a large group such as Cbz are more active than compounds with a small group such as Ac. Compounds with more hydrophobic protecting groups were found to be more active in cell apoptosis protection assays, probably due to increased cell permeability. MX1122, 2,4-di-Cl-Cbz-Val-Asp-fmk, is identified as a potent broad-spectrum caspase inhibitor and is selective for caspases versus other proteases, with good activity in the cell apoptosis protection assays as well as good efficacy in the mouse liver apoptosis model.     

An In Situ Formed Surface Coating Layer Enabling LiCoO2 with Stable 4.6 V High‐Voltage Cycle Performances

The development of high‐voltage LiCoO₂ is essential for achieving lithium‐ion batteries with high volumetric energy density, however, it faces a great deal of challenges owing to the materials, structure and interfacial instability issues. In this work, a strategy is developed, through heat annealing a precoated surface layer to in situ form a high‐voltage‐stable surface coating layer, which is demonstrated to be highly effective to improve the high‐voltage performance of LiCoO₂. It is discovered that LiCoO₂ reacts with Li_1.5Al_0.5Ti_1.5(PO₄)₃ (LATP) at 700 °C to form exclusively spinel phases in addition to Li₃PO₄, which are structurally coherent to the layered lattice of LiCoO₂. The heat annealing of the precoated thin layer of LATP enables the formation of a high‐quality surface layer. Spinel phases possess high‐voltage‐stable structures with much weaker oxidizing ability of lattice oxygen than layered structure. In addition, the Li₃PO₄ is a good lithium‐ion conductor with excellent chemical stability at high voltages. All these benefits contribute to the construction of a uniform and conformal high‐voltage‐stable surface layer with favorable lithium conducting kinetics at the LiCoO₂ surface. The modified LiCoO₂ shows excellent 4.6 V high‐voltage cycle performance at both room temperature and 45 °C. The thermal stability is greatly enhanced as well.