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.     

脂肪组织源性干细胞研究进展

增加具有完整功能的种子细胞数目是细胞移植的首要环节。近来研究发现,成体动物脂肪组织中含有大量的具有多向分化潜能的间充质干细胞,在特定条件下可分化为多种组织细胞,如脂肪细胞、成骨细胞、软骨细胞、肌细胞及神经星状细胞等,且具有极强的自我复制能力,有望成为组织工程理想的种子细胞。本文综述了脂肪组织源性干细胞（ADSCs）的发现、生物学特性、多向分化潜能、应用前景及存在的问题。     

半干旱区湿地-干草原交错带边界判定及其变化

鉴于目前国内对于半干旱区及小尺度上湿地-干草原交错带边界界定的研究较少,利用交错带对其周围环境变化具有提前指示作用的原理,以宁夏盐池四儿滩湿地为例,首先探讨游动分割窗技术在半干旱区湿地-干草原交错带边界判定中的可行性,其次再对2006年—2010年湿地-干草原交错带的宽度和边界进行判定,通过交错带的宽度和边界变化并结合交错带内植被的变化情况,综合对整个湿地生态系统的健康状况和湿地退化进行研究。结果表明:研究的尺度大小以及交错带过渡性是否明显将决定适宜窗口宽度的大小,这点在选择最小适宜窗口宽度时体现更为显著;降雨量是决定该区交错带的位置与宽度的最主要因素,但降雨量并不是决定该区交错带内植被变化状况的最主要因素,交错带距湿地核心区的距离是影响交错带内物种丰富度指数变化的最主要因素;由于保护区的成立,四儿滩湿地在2006年—2007年间,交错带宽度变大,湿地状况转好,2008年—2010年,由于铁路建设,湿地遭到破坏,交错带萎缩,湿地出现退化现象。湿地-干草原交错带作为一个敏感地带,它的变化情况可以对整个湿地生态系统的变化情况作出一定的提前预示;在半干旱区湿地的健康评价和退化研究中,通过交错带的变化来反映整个湿地生态系统的健康情况是一种可行的思路和方法。     

经济学视角下的流域生态补偿制度——基于一个污染赔偿的算例

近年来,随着流域水污染问题日益严重,流域上下游之间的利益冲突日趋明显,流域生态补偿成为协调流域上下游利益冲突的重要途径。虽然我国一些地区已经开展了流域生态补偿的实践,并取得了一定成效,但在具体执行中还存在许多问题。通过分析不同制度安排下流域上下游利益相关者的福利变化,来说明制度的重要作用。在介绍有关制度的重要概念后,通过比较"囚徒困境"和"囚徒梦想"两个博弈案例,指出了制度安排对效率的重要影响,即效率和公平的是由现有制度安排决定的,在每一种制度安排下,效率和公平的含义会有所不同。基于一个流域污染赔偿的算例,分析了四种制度安排下的效率差异。在这个例子中,甲代表上游的排放污水的企业,乙代表下游受害的居民。在第一种制度安排下,甲不用考虑对乙造成的损失,双方的总收益实现了最大化,但大多数人会认为这种制度安排对乙不公平。在后三种"更公平"的制度安排下,存在着对乙的利益进行补偿的不同方案,且在第三种制度安排下,双方的总收益同样达到了最大化,只有在对甲进行强制的制度安排下(即强制要求甲安装污水处理设施),双方的总收益均少于其它三种制度。对案例的分析表明:(1)通过设计合理的制度,公平和效率可以"兼得";(2)如果利益相关者拥有影响制度安排的机会,将能够促进社会公平。研究为决策者提供一个分析框架,对缓解目前流域生态补偿中上下游的利益冲突具有重要的意义。     

Long COVID and its Management

The pandemic of COVID-19 is the biggest public health crisis in 21^st Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.     

城镇化背景下深圳典型流域鱼类群落特征及驱动因子

理解城镇的快速发展对河流鱼类群落结构的影响,是城镇河流科学管理和生物多样性保护的关键基础。本研究于2019年丰水期（8月）和枯水期（11月）,选取我国城镇化典型城市-深圳域内两个处于不同城镇化程度的代表性流域,应用多重统计方法比较分析了流域间鱼类群落结构的差异,并探讨了驱动鱼类群落变异的关键环境要素。结果发现,城镇化程度高的观澜河流域其鱼类种类组成、优势类群、生物多样性指数与城镇化程度低的坪山河流域有明显差别。 具体表现为：城镇化程度高的流域土著敏感种类如异鱲、吸鳅等几近消失,优势类群为外来入侵耐受种类,其物种多样性显著低于城镇化程度低的流域（P<0.05）。同时,外来鱼类在城镇河段其数量占比平均达92.5%,广泛分布于深圳城镇河流中。在环境因素方面,城镇化程度高的观澜河流域水体理化指标总氮、总磷、氨氮、化学需氧量、生化需氧量、高锰酸盐指数均显著性高于城镇化程度低的坪山河流域（P<0.05）。基于Bray-Curtis距离的冗余分析显示：城镇用地占比和总氮是影响观澜河和坪山河流域鱼类群落差异的主要因素。城镇化进程中河流生境的改变已影响到土著鱼类的生物多样性。因此,推动以恢复土著鱼类生物多样性的河流生态治理与保护是今后水生态目标管理的重要方向。     

体外重构STUB1介导α-1抗胰蛋白酶突变体Z蛋白泛素化修饰反应体系

α-1抗胰蛋白酶Z型突变体蛋白(α-1 antitrypsin Z-mutant protein, ATZ)是引发α-1抗胰蛋白酶缺陷症(α-1 antitrypsin deficiency, AATD)的主要原因,研究ATZ蛋白的泛素化修饰和降解对于治疗AATD具有重要意义。STUB1是一种重要的E3泛素连接酶,参与调节多种蛋白质的泛素化修饰。然而,STUB1是否参与ATZ的泛素化修饰尚未明确。本研究首先将ATZ和STUB1的编码基因克隆到pET28a质粒,构建了这2个蛋白的表达质粒。随后,将重组质粒转入大肠杆菌表达系统,在优化诱导条件实现了重组蛋白的异源表达。通过金属螯合亲和层析技术纯化得到目的蛋白,并通过蛋白质谱分析验证了其氨基酸序列的准确性。利用纯化的ATZ和STUB1重组蛋白,构建了一个体外泛素化修饰反应体系。实验结果显示,在ATP、E1泛素激活酶和E2泛素结合酶的协同作用下,STUB1成功催化了ATZ的泛素化修饰。本研究提供了一种体外获得Z型突变体ATZ纯化蛋白的方法,并确认了STUB1介导ATZ的泛素化修饰功能,推进了对α-1抗胰蛋白酶Z型突变体蛋白在细胞内降解过程的调控机制的理解。     

ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression

Hepatocellular carcinoma is one of the most common malignant tumors.M6A is a novel epigenetic modification that have been emerged as vital regulators for the progression of HCC. However, the regulatory role, clinical significance and the details of the modification, such as the impact on the local tumor environment, remain largely unclear. Our study showed that ALKBH5 was highly expressed in HCC and high ALKBH5 expression predicted a worse prognosis of HCC patients. Prediction of ALKBH5 function by tissue samples and single cell sequencing Gene Set Variation Analysis. Primary CD3 + T lymphocytes and bone marrow-derived macrophages were used to evaluate the effect of ALKBH5 on immune microenvironment. The results indicated that ALKBH5 promote HCC cell proliferation, metastasis and PD-L1+macrophage recruitment. Mechanistically the results showed that ALKBH5 regulates MAP3K8 expression in a m6A dependent manner which mediates the proliferation and metastasis of HCC cells. ALKBH5 also promotes the activation of JNK and ERK pathways through upregulating MAP3K8, thus regulating the expression of IL-8 and promoting macrophage recruitment. Taken together, these data show that ALKBH5 promotes HCC growth, metastasis and macrophage recruitment through ALKBH5/MAP3K8 axis and it may serve as a potential diagnostic marker and target for treatment of HCC patients.