Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer

A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC₅₀ value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC₅₀ value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.     

TEB/POLQ plays dual roles in protecting Arabidopsis from NO-induced DNA damage

Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity.     

Rapid improvement of rice eating and cooking quality through gene editing toward glutelin as target

Rice eating and cooking quality(ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content(GPC) is negatively related to ECQ,making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein gluteli...     

Rhizosphere soil bacterial communities and nitrogen cycling affected by deciduous and evergreen tree species

Deciduous and evergreen trees differ in their responses to drought and nitrogen (N) demand. Whether or not these functional types affect the role of the bacterial community in the N cycle during drought remains uncertain. Two deciduous tree species (Alnus cremastogyne, an N₂‐fixing species, and Liquidambar formosana) and two evergreen trees (Cunninghamia lanceolata and Pinus massoniana) were used to assess factors in controlling rhizosphere soil bacterial community and N cycling functions. Photosynthetic rates and biomass production of plants, 16S rRNA sequencing and N‐cycling‐related genes of rhizosphere soil were measured. The relative abundance of the phyla Actinobacteria and Firmicutes was higher, and that of Proteobacteria, Acidobacteria, and Gemmatimondaetes was lower in rhizosphere soil of deciduous trees than that of evergreen. Beta‐diversity of bacterial community also significantly differed between the two types of trees. Deciduous trees showed significantly higher net photosynthetic rates and biomass production than evergreen species both at well water condition and short‐term drought. Root biomass was the most important factor in driving soil bacterial community and N‐cycling functions than total biomass and aboveground biomass. Furthermore, 44 bacteria genera with a decreasing response and 46 taxa showed an increased response along the root biomass gradient. Regarding N‐cycle‐related functional genes, copy numbers of ammonia‐oxidizing bacteria (AOB) and autotrophic ammonia‐oxidizing archaea (AOA), N₂ fixation gene (nifH), and denitrification genes (nirK, nirS) were significantly higher in the soil of deciduous trees than in that of the evergreen. Structural equation models explained 50.2%, 47.6%, 48.6%, 49.4%, and 37.3% of the variability in copy numbers of nifH, AOB, AOA, nirK, and nirS, respectively, and revealed that root biomass had significant positive effects on copy numbers of all N‐cycle functional genes. In conclusion, root biomass played key roles in affecting bacterial community structure and soil N cycling. Our findings have important implications for our understanding of plants control over bacterial community and N‐cycling function in artificial forest ecosystems.     

Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19

There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic.     

冀北承德地区土壤生源要素生态化学计量与空间分异特征

土壤生源要素生态化学计量和空间分异特征对指导土地利用优化具有重要意义。以京津冀生态屏障区组成部分的承德市为研究区,采集1597件土壤样品,运用地统计学、全局Moran′s I指数、克里金插值和冗余分析等方法对承德全域主要土壤生源要素的空间分异特征及其影响因素进行了系统分析。结果表明,承德市表层土壤生源要素全钾(STK)、有机碳(SOC)、全氮(STN)、全磷(STP)和全硫(STS)平均含量分别为21.962 g/kg、18.826 g/kg、1.168 g/kg、0.587 g/kg和0.193 g/kg。垂向分布上STN、SOC和STS含量总体随深度增加而降低,STK和STP垂向分异受成土母质控制,高地质背景区STK和STP含量随深度增加逐渐升高。SOC和STN含量显著相关,空间耦合程度高,C:S与SOC含量显著正相关,C:N和C:S空间分布稳定,土壤生源要素的化学计量比主要受SOC含量控制。SOC空间自相关极显著,空间分异受结构性因素控制;STK空间自相关程度较高,分布稳定;STP空间自相关较显著,分布异质性较大;STS空间自相关相对最弱,受人为活动影响较明显。SOC和STN空间...     

风速变化对草原生态系统的影响研究进展

在全球风速呈下降趋势的大背景下,研究风速变化对生态系统的影响具有重要意义,尤其是其重要组成部分——草原生态系统。近年来大量学者开始研究风速变化对草原生态系统的影响,主要集中在以下几个方面并得出相关的结论,(1)风速变化会影响植物的生长速率和叶片形态,适当的风速能够促进植物生长发育、提高植被初级生产力,而强风或持续大风不仅会对植物产生破坏作用,还会影响其生长发育;(2)风会最先带走地表细小颗粒,从而导致土壤质地变粗、水分下降、营养成分重新分配;(3)风引起地表边界层和大气边界层物质和能量的转移和交换,热量和水汽的交换导致地表微气候发生变化,如风速降低会导致地表温度升高;(4)风力作用使得土壤水分亏缺、营养成分变化,导致草原生态系统结构变化、草地覆盖度降低、物种生活型复杂化、耐旱植物增加;(5)大气稳定性、CO2交换速率和碳排放都会随着风速的增加而增加,碳吸收则相反,碳通量也因此发生变化。综上,风速降低对于草原生态系统的影响复杂且利弊相当,未来的发展趋势会更加侧重于以下几个方面的发展:研究对象的多样化、加强控制实验的定量化研究、综合多要素的相互作用机理研究、整体结构和功能性的研究。