Crystal Structural Framework of Lithium Super‐Ionic Conductors

As technologically important materials for solid‐state batteries, Li super‐ionic conductors are a class of materials exhibiting exceptionally high ionic conductivity at room temperature. These materials have unique crystal structural frameworks hosting a highly conductive Li sublattice. However, it is not understood why certain crystal structures of the super‐ionic conductors lead to high conductivity in the Li sublattice. In this study, using topological analysis and ab initio molecular dynamics simulations, the crystal structures of all Li‐conducting oxides and sulfides are studied systematically and the key features pertaining to fast‐ion conduction are quantified. In particular, a unique feature of enlarged Li sites caused by large local spaces in the crystal structural framework is identified, promoting fast conduction in the Li‐ion sublattice. Based on these quantified features, the high‐throughput screening identifies many new structures as fast Li‐ion conductors, which are further confirmed by ab initio molecular dynamics simulations. This study provides new insights and a systematic quantitative understanding of the crystal structural frameworks of fast ion‐conductor materials and motivates future experimental and computational studies on new fast‐ion conductors.     

MobiSeq: De novo SNP discovery in model and non‐model species through sequencing the flanking region of transposable elements

In recent years, the availability of reduced representation library (RRL) methods has catalysed an expansion of genome‐scale studies to characterize both model and non‐model organisms. Most of these methods rely on the use of restriction enzymes to obtain DNA sequences at a genome‐wide level. These approaches have been widely used to sequence thousands of markers across individuals for many organisms at a reasonable cost, revolutionizing the field of population genomics. However, there are still some limitations associated with these methods, in particular the high molecular weight DNA required as starting material, the reduced number of common loci among investigated samples, and the short length of the sequenced site‐associated DNA. Here, we present MobiSeq, a RRL protocol exploiting simple laboratory techniques, that generates genomic data based on PCR targeted enrichment of transposable elements and the sequencing of the associated flanking region. We validate its performance across 103 DNA extracts derived from three mammalian species: grey wolf (Canis lupus), red deer complex (Cervus sp.) and brown rat (Rattus norvegicus). MobiSeq enables the sequencing of hundreds of thousands loci across the genome and performs SNP discovery with relatively low rates of clonality. Given the ease and flexibility of MobiSeq protocol, the method has the potential to be implemented for marker discovery and population genomics across a wide range of organisms—enabling the exploration of diverse evolutionary and conservation questions.     

Kallikrein 5 inhibitors identified through structure based drug design in search for a treatment for Netherton Syndrome

Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10–100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology.     

关联分析在作物种质资源分子评价中的应用

发掘优异基因资源是作物种质资源分子评价的重要部分,对作物育种尤其是分子育种具有非常重要的实践意义。基于连锁不平衡(LD)的关联分析是基因发掘也是等位基因发掘的有效途径。本文系统介绍了关联分析的基本理论、策略、特点及应用现状,并探讨了其在作物种质资源新(等位)基因发掘中的发展趋势及展望。可以预见,与传统QTL作图及功能基因组学相整合的关联分析必将大大加快我国作物种质资源的研究进程,实现我国种质资源优势向基因资源优势的转变。     

Drugging the undruggable proteins in cancer: A systems biology approach

In recent years, the research community has, with comprehensive systems biology approaches and related technologies, gained insight into the vast complexity of numerous cancers. These approaches allow an in-depth exploration that cannot be achieved solely using conventional low-throughput methods, which do not closely mimic the natural cellular environment. In this review, we discuss recent integrative multiple omics approaches for understanding and modulating previously identified ‘undruggable’ targets such as members of the RAS family, MYC, TP53, and various E3 ligases and deubiquitinases. We describe how these technologies have revolutionized drug discovery by overcoming an array of biological and technological challenges and how, in the future, they will be pivotal in assessing cancer states in individual patients, allowing for the prediction and application of personalized disease treatments.     

绿绒蒿属一中国新记录种——尼东绿绒蒿

中国西藏植物多样性较为丰富,尽管已经进行了多次的植物多样性调查,但仍存在较严重的不均衡现象,部分地区和类群存在采集不足,甚至空白。我们针对西藏日喀则植物多样性调查薄弱区域开展调查,发现一个未记录的绿绒蒿属(Meconopsis Viguier)植物,采集了标本和种子。经查阅《西藏植物志》《中国植物志》、Flora of China、Flora of Nepal鉴定为尼东绿绒蒿(M. dhwojii G. Taylor ex Hay)。该文植物新资料报道如下:(1)尼东绿绒蒿形态描述及其彩色图片。(2)该植物种子微形态、与近似种间的形态差异。新发现丰富了中国绿绒蒿属植物多样性,对研究西藏乃至中国绿绒蒿属植物具有一定的生物地理学意义和潜在的园艺价值。绿绒蒿属分类须加强野外调研,多技术手段开展研究。     

Viridiflorol induces anti-neoplastic effects on breast,lung, and brain cancer cells through apoptosis

All active natural molecules are not fully exploited as therapeutic agents, causing delays in the advancement of anticancer drug discovery. Viridiflorol is a natural volatile element that may work as anti-cancer compound. We tested the anticancer properties of viridiflorol at different concentrations ranging from 0.03 to 300 μM in vitro on three cancer cells including breast (MCF-7), lung (A549) and brain (Daoy). The cancer cells responses were documented after treatment using MTT and Annexin V assays. Viridiflorol showed cytotoxic effects against all tested cell lines, reducing cell viability in a concentration-dependent manner with variable IC₅₀ values. Daoy and A549 cell lines were more sensitive to viridiflorol when compared with temozolomide and doxorubicin, respectively. Viridiflorol demonstrated the highest anticancer activity against the Daoy cells with an estimated IC₅₀ of 0.1 µM followed by MCF-7 at 10 µM, and A549 at 30 µM. In addition, upon exposure to concentrations ranging from 30 µM to 300 µM of viridiflorol, early and late apoptotic cell death was induced in a concentration dependent manner in Daoy (55.8%-72.1%), MCF-7 (36.2%-72.7%) and A459 (35%-98.9%) cell lines, respectively. In conclusion, viridiflorol demonstrates cytotoxic and apoptotic ability in three different cancer cell lines (brain, breast and lung).     

Dynamic mass spectrometry probe for electrospray ionization mass spectrometry monitoring of bioreactors for therapeutic cell manufacturing

Large-scale manufacturing of therapeutic cells requires bioreactor technologies with online feedback control enabled by monitoring of secreted biomolecular critical quality attributes (CQAs). Electrospray ionization mass spectrometry (ESI-MS) is a highly sensitive label-free method to detect and identify biomolecules, but requires extensive sample preparation before analysis, making online application of ESI-MS challenging. We present a microfabricated, monolithically integrated device capable of continuous sample collection, treatment, and direct infusion for ESI-MS detection of biomolecules in high-salt solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass exchanger to rapidly condition samples for online MS analysis by removing interfering salts, while concurrently introducing MS signal enhancers to the sample for sensitive biomolecular detection. Exploiting this active conditioning capability increases MS signal intensity and signal-to-noise ratio. As a result, sensitivity for low-concentration biomolecules is significantly improved, and multiple proteins can be detected from chemically complex samples. Thus, the DMSP has significant potential to serve as an enabling portion of a novel analytical tool for discovery and monitoring of CQAs relevant to therapeutic cell manufacturing.