Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model

Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.     

斑纹小贻贝(Mytella strigata)基础生物学与生物入侵

生物入侵是继栖息地破坏之后，全球生物多样性丧失的第二大驱动因素。近年来，原产于南美洲地区的斑纹小贻贝（Mytella strigata）在印度-西太平洋海区被陆续报道，而我国台湾、广东、海南、福建、广西等省份同样发现斑纹小贻贝，且其已经建立可自我维持的种群。但是，作为一种新型入侵生物，斑纹小贻贝尚未引起国内海洋管理部门和科研人员足够重视，亟待查明其在我国沿海的分布现状、扩散趋势和生态影响等，为斑纹小贻贝的检测、监测、防控和管理提供科学依据。综述了斑纹小贻贝的基础生物学特征和全球生物入侵现状，发现国内的斑纹小贻贝源于南美洲加勒比海地区，于2014年左右通过船舶压舱水或船体生物污损的形式侵入我国南方沿海并迅速扩散。此外，斑纹小贻贝在我国的生物入侵处于"引进-传播"阶段，即将大规模扩繁，因此亟需开展应急清除行动。     

濒危植物永瓣藤叶片功能性状对环境因子的响应

植物叶片功能性状能够响应环境条件的变化，反应了植物对环境的适应策略。当前，针对藤本植物叶片功能性状地理格局及其环境驱动力的研究较少。以国家重点保护植物永瓣藤（Monimopetalum chinense）为研究对象，对其分布区内11个种群的15个叶片功能性状进行测量，并结合气候、土壤因子来解释叶性状变异。比较叶片性状在局域和区域尺度上的种内变异程度，利用多元逐步回归分析环境因子对叶性状的影响。结果表明，在局域尺度上，永瓣藤叶功能性状变异系数介于3.0%-22.5%，其中，叶面积变异程度最大，叶片碳含量变异最小。永瓣藤叶片形状随纬度上升而变得宽且圆。叶片磷含量相对较低，永瓣藤的生长可能受到了磷限制。土壤与气候因子是叶片性状的重要驱动因素，解释了25%-97%的叶片性状变异。在温度和水分充足的情况下，永瓣藤叶片趋向于的慢速生长的保守策略。总体来说，永瓣藤叶片功能性状通过一定的种内变异和性状组合，并与气候、土壤因子相互作用，适应当前的环境条件。     

基于MODIS NDVI的长江中游区域植被动态及与气候因子的关系

基于1999-2015年的MODIS NDVI时间序列遥感数据，应用趋势分析、变异系数、重标极差分析和偏相关分析等方法，分析了长江中游的植被时空变化特征及其与气象因子的关系。结果表明，长江中游地区NDVI均值总体上呈上升趋势（从0.72增加到0.80）。从空间分布来看，NDVI低值区域（0.1-0.5）占1.40%，高值区域（>0.7）占87.15%；NDVI空间格局呈"西高东低、北高南低"的分布特征，低值区域表现为以三省省会城市为中心向外辐射。Hurst指数显示，研究区大部分区域（60.54%）的NDVI变化趋势具有不确定性，持续性改善区域（34.78%）主要分布在西部山地区，持续性退化区域（3.26%）主要分布在人类活动频繁的较发达城市区域。在年际尺度上，研究区NDVI与各气象因子关系均不显著；月际尺度上，NDVI与降水、相对湿度和日照时数显著相关，降水和日照时数有明显的时滞性。区域内NDVI动态趋势以不确定性发展为主，城市群周边NDVI呈现持续退化的区域应该引起关注。     

Inhibitory effect of aspirin on cholera toxin-induced phospholipase and cyclo-oxygenase activity

Cholera toxin (CT) stimulated phospholipase activity and caused [3H]arachidonic acid (3H-AA) release in a murine macrophage/monocyte cell line. Pretreatment of cells with dexamethasone, a phospholipase A2 (PLA2) inhibitor, did not affect CT-induced 3H-AA release. In contrast, aspirin, which is an inhibitor of phospholipase C (PLC), blocked CT-induced 3H-AA release and subsequent prostaglandin (PC) synthesis. The inhibitory effect of aspirin was dose dependent, with 4 mM reducing the CT response by approximately 50%. Similarly, inhibition was time dependent, occurring when the drug was added to the culture medium as late as 30 min after CT. Brief exposure (30 min) of the cells to aspirin did not alter their subsequent response to CT, but 3H-AA release from cells exposed to aspirin for 2.5 h was irreversibly inhibited. The data suggested that CT stimulation of AA metabolism may involve increased PLC activity.     

Genome Sequence and Comparative Genomics Analysis of a Vibrio cholerae O1 Strain Isolated from a Cholera Patient in Malaysia

The genome sequence analysis of a clinical Vibrio cholerae VC35 strain from an outbreak case in Malaysia indicates multiple genes involved in host adaptation and a novel Na⁺-driven multidrug efflux pump-coding gene in the genome of Vibrio cholerae with the highest similarity to VMA_001754 of Vibrio mimicus VMA223.     

Module-based construction of plasmids for chromosomal integration of the fission yeast Schizosaccharomyces pombe

Integration of an external gene into a fission yeast chromosome is useful to investigate the effect of the gene product. An easy way to knock-in a gene construct is use of an integration plasmid, which can be targeted and inserted to a chromosome through homologous recombination. Despite the advantage of integration, construction of integration plasmids is energy- and time-consuming, because there is no systematic library of integration plasmids with various promoters, fluorescent protein tags, terminators and selection markers; therefore, researchers are often forced to make appropriate ones through multiple rounds of cloning procedures. Here, we establish materials and methods to easily construct integration plasmids. We introduce a convenient cloning system based on Golden Gate DNA shuffling, which enables the connection of multiple DNA fragments at once: any kind of promoters and terminators, the gene of interest, in combination with any fluorescent protein tag genes and any selection markers. Each of those DNA fragments, called a ‘module’, can be tandemly ligated in the order we desire in a single reaction, which yields a circular plasmid in a one-step manner. The resulting plasmids can be integrated through standard methods for transformation. Thus, these materials and methods help easy construction of knock-in strains, and this will further increase the value of fission yeast as a model organism.     

气候变化和人类活动对中国北方旱区植被变绿的定量贡献

气候变化和大规模的生态恢复使中国北方旱区植被发生了显著变化，量化气候变化和人类活动对植被动态的相对贡献，对于旱区生态系统管理和应对未来气候变化具有重要意义。目前，中国北方旱区植被变化影响因素的时间动态（2000年大规模生态恢复工程实施前后）和空间异质性（沿干旱梯度）仍需进一步的定量研究。基于多源数据，采用趋势分析、偏相关分析和随机森林模型等方法，分析了1981-2018年中国北方旱区气候和植被的时空变化规律，量化了2000年前后气候变化和人类活动对植被动态的相对贡献并分析其在干旱梯度上的空间差异性。结果表明：（1）1981-2018年期间，中国北方旱区的叶面积指数（LAI）平均增加速率为（0.0037±0.0443） a^-1，且增加速率沿干旱梯度增大。2000年前仅10.46%（P<0.05）的地区显著变绿，而2000年后达到36.84%，且植被变绿主要归因于非树木植被。（2）2000年后降水对植被变绿的正效应在不同干旱梯度均增加，而在半干旱区和亚湿润干旱区，温度对植被变绿由正向促进转为负向抑制，而辐射在干旱区由负效应转向正效应。（3）2000年前后，气候变化均主导着植被的动态，贡献率分别为96.07%和73.72%，人类活动的贡献在2000年后进一步增强（从3.93%增加到26.28%），且沿着干旱梯度而增加，其中人类活动对植被变绿的贡献在半干旱地区增加最显著（+0.0289 m² m^-2 a^-1，P<0.05）。研究结果可为未来气候变化下中国北方旱区的植被恢复和可持续发展提供科学依据。