Base excision repair but not DNA double‐strand break repair is impaired in aged human adipose‐derived stem cells

The decline in DNA repair capacity contributes to the age‐associated decrease in genome integrity in somatic cells of different species. However, due to the lack of clinical samples and appropriate tools for studying DNA repair, whether and how age‐associated changes in DNA repair result in a loss of genome integrity of human adult stem cells remains incompletely characterized. Here, we isolated 20 eyelid adipose‐derived stem cell (ADSC) lines from healthy individuals (young: 10 donors with ages ranging 17–25 years; old: 10 donors with ages ranging 50–59 years). Using these cell lines, we systematically compared the efficiency of base excision repair (BER) and two DNA double‐strand break (DSB) repair pathways—nonhomologous end joining (NHEJ) and homologous recombination (HR)—between the young and old groups. Surprisingly, we found that the efficiency of BER but not NHEJ or HR is impaired in aged human ADSCs, which is in contrast to previous findings that DSB repair declines with age in human fibroblasts. We also demonstrated that BER efficiency is negatively associated with tail moment, which reflects a loss of genome integrity in human ADSCs. Mechanistic studies indicated that at the protein level XRCC1, but not other BER factors, exhibited age‐associated decline. Overexpression of XRCC1 reversed the decline of BER efficiency and genome integrity, indicating that XRCC1 is a potential therapeutic target for stabilizing genomes in aged ADSCs.     

The protective effects of C16 peptide and angiopoietin-1 compound in lipopolysaccharide-induced acute respiratory distress syndrome

C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C  +  A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO₂), decreased arterial carbon dioxide partial pressure (PCO₂), and increased oxygen partial pressure (PO₂) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C  +  A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.     

HIF‐1α forms regulatory loop with YAP to coordinate hypoxia‐induced adriamycin resistance in acute myeloid leukemia cells

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl₂ can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML.     

TREEasy: An automated workflow to infer gene trees,species trees,and phylogenetic networks from multilocus data

Multilocus genomic data sets can be used to infer a rich set of information about the evolutionary history of a lineage, including gene trees, species trees, and phylogenetic networks. However, user‐friendly tools to run such integrated analyses are lacking, and workflows often require tedious reformatting and handling time to shepherd data through a series of individual programs. Here, we present a tool written in Python—TREEasy—that performs automated sequence alignment (with MAFFT), gene tree inference (with IQ‐Tree), species inference from concatenated data (with IQ‐Tree and RaxML‐NG), species tree inference from gene trees (with ASTRAL, MP‐EST, and STELLS2), and phylogenetic network inference (with SNaQ and PhyloNet). The tool only requires FASTA files and nine parameters as inputs. The tool can be run as command line or through a Graphical User Interface (GUI). As examples, we reproduced a recent analysis of staghorn coral evolution, and performed a new analysis on the evolution of the “WGD clade” of yeast. The latter revealed novel patterns that were not identified by previous analyses. TREEasy represents a reliable and simple tool to accelerate research in systematic biology ( https://github.com/MaoYafei/TREEasy ).     

Effect of woody plant expansion on decomposition of fine root mixtures in a grass-dominated temperate wetland

Wetlands Ecology and Management - Little is known about the effect of woody plant expansion on decomposition of root mixtures in grass-dominant temperate wetlands. Here, we collected fine roots...     

二氢乳清酸脱氢酶的结构特征和催化循环研究进展

二氢乳清酸脱氢酶是黄素依赖的线粒体酶,它催化嘧啶从头合成的第4步反应,将二氢乳清酸氧化为乳清酸。通过选择性抑制二氢乳清酸脱氢酶,从而抑制嘧啶的合成,已被开发用于治疗癌症、自身免疫性疾病、细菌或病毒感染以及寄生虫疾病等。抑制剂的开发需详细了解二氢乳清酸脱氢酶的结构特征和催化循环机制。因此,文中主要从这两个方面进行了综述,并展望了该酶的抑制剂在临床应用中的前景。     

四川黑竹沟地区非飞行小型兽类物种多样性与群落组成

四川黑竹沟国家级自然保护区位于生物多样性丰富的凉山山系, 在保护和维持区域生物多样性方面具有极其重要的地位, 然而对该自然保护区兽类群落的研究却极为缺乏。为了了解该自然保护区及周边的小型兽类群落,本文作者在2018年4-10月调查了该区域的非飞行小型兽类物种多样性及其群落组成。在海拔1,537-3,830 m间共设置样方184个, 布设鼠夹9,016铗日, 捕获小型兽类536只, 隶属4目7科13属21种。包括滇攀鼠(Vernaya fulva)和等齿鼩鼹(Uropsilus aequodonenia)两个稀有物种在内的共计9个物种为该地区首次报道, 丰富了物种分布记录。结合历史资料, 黑竹沟地区共记录小型兽类43种, 隶属4目9科28属。在43种小型兽类中, 东洋界物种37种, 占绝对优势(86%), 分布型以喜马拉雅-横断山型占优, 为18种(占东洋界48.6%)。本次调查捕获的21种小型兽类中, 群落优势种为中华姬鼠(Apodemus draco, 33.2%)、北社鼠(Niviventer confucianus, 21.3%)和中华绒鼠(Eothenomys chinensis, 12.7%)。随着海拔上升, 群落优势种组成发生变化, 由北社鼠 + 中华姬鼠 + 针毛鼠(Niviventer fulvescens) + 短尾鼩(Anourosorex squamipes)群落, 转变为中华绒鼠 + 中华姬鼠 + 凉山沟牙田鼠(Proedromys liangshanensis) + 西南绒鼠(Eothenomys custos)群落。群落物种区系的分布型组成随着海拔升高而发生变化, 喜马拉雅-横断山型物种随海拔升高所占比例增大; 分布于喜马拉雅-横断山的特有种分布的下限、中点和上限平均海拔都高于非特有种, 且特有种和非特有种的中点和下限平均海拔差异显著(n = 21, df = 19, P = 0.013; n = 21, df = 19, P < 0.01), 说明该区域物种具有明显的东洋界特征, 中高海拔主要由特有种构成。本研究丰富了黑竹沟地区小型兽类及群落多样性的数据资料, 有利于该地区物种多样性的研究和保护。     

Allopatric divergence and hybridization within Cupressus chengiana (Cupressaceae), a threatened conifer in the northern Hengduan Mountains of western China

Having a comprehensive understanding of population structure, genetic differentiation and demographic history is important for the conservation and management of threatened species. High‐throughput sequencing (HTS) provides exciting opportunities to address a wide range of factors for conservation genetics. Here, we generated HTS data and identified 266,884 high‐quality single nucleotide polymorphisms from 82 individuals of Cupressus chengiana, to assess population genomics across the species' full range, comprising the Daduhe River (DDH), Minjiang River (MJR) and Bailongjiang River (BLJ) catchments in western China. admixture , principal components analysis and phylogenetic analyses indicated that each region contains a distinct lineage, with high levels of differentiation between them (DDH, MJR and BLJ lineages). MJR was newly distinguished compared to previous surveys, and evidence including coalescent simulations supported a hybrid origin of MJR during the Quaternary. Each of these three lineages should be recognized as an evolutionarily significant unit (ESU), due to isolation, differing genetic adaptations and different demographic history. Currently, each ESU faces distinct threats, and will require different conservation strategies. Our work shows that population genomic approaches using HTS can reconstruct the complex evolutionary history of threatened species in mountainous regions, and hence inform conservation efforts, and contribute to the understanding of high biodiversity in mountains.