Sestrin 2 attenuates sepsis‐associated encephalopathy through the promotion of autophagy in hippocampal neurons

Sepsis‐associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno‐associated virus 2 (AAV2)‐mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2‐16 hours following CLP. AAV2‐mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro‐inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc‐51‐like kinase 1 (ULK1)‐dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI‐0206965 blocked SESN2‐mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1‐dependent autophagy in hippocampal neurons.     

Climate change impacts on asphalt road pavement construction and maintenance: An economic life cycle assessment of adaptation measures in the State of Virginia,United States

Pavement design and management practices must be adapted in response to future climate change. While many studies have attempted to identify different methods to adapt pavements to future climate conditions, the potential economic impacts of the adaptations still remain largely unquantified. This study presents the results of a comprehensive life‐cycle cost analysis (LCCA) aimed at quantifying the potential economic impacts of a climate adaptation method, in which an upgraded asphalt binder (Performance Grade PG 76‐22) is used in the construction and maintenance of flexible pavement sections in lieu of the original binder (PG 70‐22) for improved resistance against high temperatures. For each of three major Virginia Department of Transportation (VDOT) districts with different climates, three case studies consisting of typical interstate, primary, and secondary pavement sections were considered. The LCCA accounted for the costs incurred during the mixture's production, maintenance, and use phases of the pavement life cycle by explicitly considering future climate projections, pavement life‐cycle performance, maintenance effects, and work zone user delays. The study concludes that pavements using the upgraded binder not only perform better over time but are also economically advantageous compared to those with the original binder under the conditions of the anticipated future climate conditions (2020–2039).     

辅色剂对紫淮山花色苷稳定性的影响及其热降解动力学研究

为探究谷胱甘肽和没食子酸对紫淮山花色苷的辅色作用,本文研究了谷胱甘肽和没食子酸对紫淮山花色苷降解率、热稳定性及色差的影响。试验表明,谷胱甘肽和没食子酸能有效抑制花色苷的降解,且最佳添加量分别为0.03%和0.2%。在此添加量条件下,紫淮山花色苷在50、70、90℃水浴中的热降解均符合一级降解反应动力学规律。添加谷胱甘肽和没食子酸的紫淮山花色苷降解速率常数(k)小于对照组,半衰期(t 1/2)和活化能(Ea)高于对照组,说明谷胱甘肽和没食子酸能够增强花色苷的热稳定性。色差测定结果表明,经谷胱甘肽和没食子酸辅色后的紫淮山花色苷,其明度指数(L*)和色品指数(a*、b*)较对照组变化缓慢,颜色的稳定性增强。     

The Fruit Dropping Characters of Sweet Cherry and Its Interior Causes in Insufficient Chilling Zone

Russian Journal of Plant Physiology - Attempts had been made to provide evidences insight into the pattern and physiological mechanism of sweet cherry fruit dropping. However, the fruit abscission...     

南亚热带人工林种植对赤红壤团聚体分布及稳定性的影响

本文选取南亚热带地区桉树、杉木、马尾松、米老排和红锥5种典型人工林为研究对象,采用Elliott湿筛法和Le Bissonnais(LB)法研究了人工林对土壤团聚体稳定性的影响。结果表明: 5种人工林土壤经湿筛法处理后,水稳性团聚体(WR_>0.25)均在62.2%以上,团聚体平均重量直径(MWD)和几何平均直径(GMD)分别介于1.58～3.71和0.57～2.02 mm,表现为杉木林最大,桉树林最小。各林分土壤团聚体结构破坏率(PAD)介于4.6%～31.5%之间;采用转移矩阵法评价5种人工林土壤团聚体,得出土壤团聚体稳定性指数(ASI)为杉木林>红锥林>米老排林>马尾松林>桉树林。在LB法3种处理下,快速湿润处理(FW)对土壤团聚体的破坏程度最大,说明消散作用是研究区团粒崩解的主要机制;预湿润振荡处理(WS)的破坏程度最小;慢速湿润处理(SW)介于两者之间,MWD和GMD值变化一致,均表现为WS>SW>FW,且随土层的加深,呈现逐渐降低的趋势。5种人工林土壤在LB法FW处理下团聚体GMD值与湿筛法ASI、MWD、GMD均达到显著正相关,表明湿筛法与LB法的FW处理具有很好的相关性,可用于表征南亚热带赤红壤地区土壤团聚体的稳定性。综合MWD、GMD、PAD和ASI等团聚体稳定性指标,杉木人工林比其他4种人工林更有助于土壤团聚水平的提高,其土壤结构相对较为稳定。     

L,D-转肽酶LdtMt2-厄他培南加合物的新状态Ⅰ-plus结构

具有多重耐药性和广泛耐药性的结核分枝杆菌菌株正在全球范围内传播,因此,迫切需要新的抗结核药物。结核分枝杆菌的L,D-转肽酶LdtMt2直接参与肽聚糖的形成,细菌毒性和β-内酰胺抗性。该酶是潜在的抗结核靶标,可以被碳青霉烯类抗生素抑制,碳青霉烯类抗生素是FDA批准的用于治疗肺结核的药物。据报道,LdtMt2与碳青霉烯类抗生素（如厄他培南,亚胺培南和美洛培南）相互作用时,存在两种不同的中间状态,即状态I和II。状态I被认为是初始加合物形成状态,而状态II被认为是稳定的蛋白质-配体相互作用状态,并伴有碳青霉烯类抗生素和蛋白质的局部构象排列。本文中,我们报告了一个LdMt2-ertapenem新中间状态I-plus,具有与状态II相同的碳青霉烯类抗生素构象和与状态I相似的局部蛋白质构象。该新状态是从状态I转变为状态II的中间状态,构象变化发生在厄他培南分子而不是蛋白质。我们的工作有助于阐明碳青霉烯类抗生素对LdtMt2的作用后发生的变化,并与其他报道的中间状态一起揭示L,D-转肽酶如何与碳青霉烯类抗生素相互作用。     

2018-2019年中国流行性腮腺炎流行特征和病毒基因特征分析

阐明中国(未包括香港、澳门特别行政区和台湾地区,下同)2018-2019年流行性腮腺炎(流腮)流行特征和病毒基因特征。对2018-2019年中国流腮流行病学和病毒学监测数据进行描述流行病学和分子流行病学分析。2018-2019年中国流腮年报告发病率分别为18.65/10万和21.48/10万,15岁以下儿童和青少年是我国流腮的高发人群,分别占总病例数的85.30%和82.56%。流腮的流行具有明显的季节性特征。全国各省、自治区、直辖市份均有流腮病例报告,西部和中部地区发病率高于东部地区。2018-2019年共获得160条腮腺炎病毒(Mumps virus,MuV)SH基因序列,其中150条(93.75%)序列鉴定为F基因型MuV,在我国11个省份检测到;10条(6.25%)序列为G基因型MuV,2019年在广东、湖北和新疆3个省份检测到。和我国既往流行MuV代表株相比,2018-2019年流行的F基因型MuV代表株序列在基因亲缘性关系树上相对集中。现阶段我国流腮的流行病学特征未发生明显改变,仍呈现病毒自然流行模式;F基因型作为优势流行基因型,在我国大部分地区持续流行,但毒株的遗传多态性有所降低,这可能和我国实施1剂次腮腺炎疫苗常规免疫策略有关。G基因型MuV主要在我国局部地区流行,但流行范围在逐渐扩大。建议进一步加强两剂次腮腺炎疫苗接种工作,降低我国腮腺炎易感人群。同时持续性开展MuV流行学和病毒学监测工作,为鉴别病毒的来源,确定病毒传播途径和评估腮腺炎疫苗免疫策略奠定重要的基础。     

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

Science China Life Sciences -     

HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1

Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer.