ArfGAP1 inhibits mTORC1 lysosomal localization and activation

The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid‐deficient conditions is not completely understood. Here, we identify ADP‐ribosylation factor GTPase‐activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature‐sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics.     

呼伦贝尔沙地樟子松径向生长特征的VS模型模拟分析

利用Vaganov-Shashkin模型对呼伦贝尔地区4个样点的沙地樟子松标准化宽度年表进行模拟研究,在2000年以前时段拟合度较好,而2000年以后时段拟合度较差。进而选取2000年以前的模拟结果进行径向生长过程分析。结果表明: 呼伦贝尔沙地樟子松主要的生长季为每年的5—9月,温度对每年樟子松生长初期与末期具有显著影响,而在树木生长季旺盛期,土壤湿度的不足是制约树木生长的主要因素。极端窄年树木径向生长速率受土壤湿度的影响较极端宽年明显,生长季中期7—8月树木径向生长速率在宽窄年份均呈降低趋势,表明该时期沙地樟子松生长均受到不同程度的干旱胁迫。研究结果与我国半干旱地区树木年轮生理模型分析特征相符,模型对呼伦贝尔沙地樟子松径向生长模拟具有一定的适用性。     

寨卡病毒,不仅仅是小头畸形

寨卡病毒(Zika virus,ZIKV)属于黄病毒科黄病毒属,由蚊虫叮咬传播。ZIKV发现于1947年。2007年以来,由于基因突变,ZIKV获得了更强的神经嗜性和在蚊虫体内播散的能力,因而在全球加快流行,并与成人吉兰-巴雷综合征和胎儿小头畸形的发生密切相关。最近的临床观察和动物研究进一步表明,ZIKV感染引起的临床症状复杂多样,所造成的疾病不仅仅是小头畸形,它还能够损伤雄性生殖系统,干扰下丘脑对神经内分泌系统的调节,引起多种激素分泌缺陷,导致生长发育迟缓和学习记忆能力损伤。因此,对于先天感染ZIKV的新生儿,不仅要在孕期监测小头畸形的发生,出生后也需进行长期的跟踪观察;对于出生后感染ZIKV的婴幼儿以及学龄前儿童,无论病情轻重,也需要进行随访,以明确ZIKV感染的远期影响。     

植物-固定化菌剂联合修复多环芳烃污染土壤

以火凤凰根际土壤中发现的3种优势菌[分枝杆菌(Ⅰ)、产黄纤维单胞菌(Ⅱ)、少动鞘氨醇单胞菌(Ⅲ)]构建的多菌剂体系为供试菌剂,针对大港油田原油污染土壤,将固定化供试菌剂接种于修复植物火凤凰根际,探讨供试菌剂强化火凤凰修复多环芳烃(PAHs)污染土壤的效果。结果表明: 处理ⅠⅢ(有效活菌数为10⁹ cfu·mL^-1)和ⅠⅡⅢ(有效活菌数为10⁷ cfu·mL^-1)对PAHs的降解有促进作用,PAHs降解率分别为32.2%和41.4%,均显著高于相应对照处理。此外,处理ⅠⅡⅢ对火凤凰的地下生物量有明显促进作用,比对照处理增加了31.2%。表明由3种优势菌构建的多菌剂ⅠⅡⅢ可以作为火凤凰修复PAHs污染土壤的强化手段,为微生物强化植物修复技术提供了新的修复思路及方法。     

Suppression of DRR1 results in the accumulation of insoluble ubiquitinated proteins,which impairs drought stress tolerance

Drought stress has detrimental effects on plants. Although the abscisic acid (ABA)‐mediated drought response is well established, defensive mechanisms to cope with dehydration‐induced proteotoxicity have been rarely studied. DRR1 was identified as an Arabidopsis drought‐induced gene encoding an ER‐localized RING‐type E3 Ub ligase. Suppression of DRR1 markedly reduced tolerance to drought and proteotoxic stress without altering ABA‐mediated germination and stomatal movement. Proteotoxicity‐ and dehydration‐induced insoluble ubiquitinated protein accumulation was more obvious in DRR1 loss‐of‐function plants than in wild‐type plants. These results suggest that DRR1 is involved in an ABA‐independent drought stress response possibly through the mitigation of dehydration‐induced proteotoxic stress.     

Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19

Science China Life Sciences -     

Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model

Background aimsCorneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs.MethodsHuman MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels.ResultsAll corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels.ConclusionsPEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries.     

Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer

IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.     

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies. The unfavourable prognosis is mainly due to the lack of early-stage diagnosis, drug resistance and recurrence. Therefore, it needs to investigate the mechanism of OC tumorigenesis and identify effective biomarkers for the clinical diagnosis. It is reported that long noncoding RNAs (lncRNAs) play important roles during the tumorigenesis of OC. Therefore, the present study aimed to study the role and clinical significance of LncRNAs ATB (lnc-ATB) in the development and progression of OC. In our research, lnc-ATB expression in OC tissues was elevated compared with adjacent normal tissues and high expression of lnc-ATB was associated with poor outcomes of OC patients. The silencing of lnc-ATB blocked cell proliferation, invasion and migration in SKOV3 and A2780 cells. RNA immunoprecipitation and RNA pull-down results showed that lnc-ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Besides, the overexpression of EZH2 partly rescued lnc-ATB silencing-inducing inhibition of cell proliferation, invasion and migration. Chromatin immunoprecipitation assay results demonstrated that the silencing of lnc-ATB reduced the occupancy of caudal-related homeobox protein 1, Forkhead box C1, Large tumour suppressor kinase 2, cadherin-1 and disabled homolog 2 interacting protein promoters on EZH2 and H3K27me3. These data revealed the oncogenic of lnc-ATB and provided a novel biomarker for OC diagnosis. Furthermore, these findings indicated the mechanism of lnc-ATB functioning in the progression of OC, which provided a new target for OC therapy.