VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment

Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.     

Comparing sources of mobility for modelling the epidemic spread of Zika virus in Colombia

Timely, accurate, and comparative data on human mobility is of paramount importance for epidemic preparedness and response, but generally not available or easily accessible. Mobile phone metadata, typically in the form of Call Detail Records (CDRs), represents a powerful source of information on human movements at an unprecedented scale. In this work, we investigate the potential benefits of harnessing aggregated CDR-derived mobility to predict the 2015-2016 Zika virus (ZIKV) outbreak in Colombia, when compared to other traditional data sources. To simulate the spread of ZIKV at sub-national level in Colombia, we employ a stochastic metapopulation epidemic model for vector-borne diseases. Our model integrates detailed data on the key drivers of ZIKV spread, including the spatial heterogeneity of the mosquito abundance, and the exposure of the population to the virus due to environmental and socio-economic factors. Given the same modelling settings (i.e. initial conditions and epidemiological parameters), we perform in-silico simulations for each mobility network and assess their ability in reproducing the local outbreak as reported by the official surveillance data. We assess the performance of our epidemic modelling approach in capturing the ZIKV outbreak both nationally and sub-nationally. Our model estimates are strongly correlated with the surveillance data at the country level (Pearson’s r = 0.92 for the CDR-informed network). Moreover, we found strong performance of the model estimates generated by the CDR-informed mobility networks in reproducing the local outbreak observed at the sub-national level. Compared to the CDR-informed networks, the performance of the other mobility networks is either comparatively similar or substantially lower, with no added value in predicting the local epidemic. This suggests that mobile phone data captures a better picture of human mobility patterns. This work contributes to the ongoing discussion on the value of aggregated mobility estimates from CDRs data that, with appropriate data protection and privacy safeguards, can be used for social impact applications and humanitarian action.     

黄土高原樟子松和落叶松与其他树种枯落叶混合分解对土壤的影响

通过采集树木枯落叶与土壤进行室内混合分解培养试验,研究了黄土高原常见的樟子松和落叶松与其他树种枯落叶混合分解对土壤性质的影响及存在的相互作用,从而为不同树木种间关系的探索和该地区人工纯林的混交改造提供科学指导。结果表明:12种枯落叶单一分解均明显提高了土壤脲酶(54%—110%)、脱氢酶(85%—288%)和磷酸酶(81%—301%)活性以及有机质(29%—55%)和碱解N(12%—49%)含量,但对土壤速效P含量和CEC的影响存在较大差异。综合而言,樟子松分别与白桦、刺槐、白榆、柠条和落叶松枯落叶混合分解在对土壤性质的影响中存在相互促进作用,而分别与小叶杨、沙棘、紫穗槐、侧柏和辽东栎枯落叶混合分解在对土壤性质的影响中存在相互抑制作用;落叶松分别与刺槐、白桦、小叶杨和紫穗槐枯落叶混合分解在对土壤性质的影响中存在相互促进作用,而分别与柠条、侧柏、辽东栎、沙棘、油松和白榆枯落叶混合分解在对土壤性质的影响中存在相互抑制作用。     

鄂尔多斯市土地利用生态安全格局构建

合理构建区域土地利用生态安全格局来实施管理对策和改善区域生态安全水平,已经成为区域生态环境保护的新需求。以位于中国北方农牧交错区的鄂尔多斯市为研究区,基于自然地理数据、社会经济统计数据、土地利用/覆被数据等,借助多目标优化模型和GIS空间分析技术,构建了鄂尔多斯市土地利用生态安全格局,结果表明:(1)不适宜性耕地所占比重较大,林地和草地分布比较合理,适宜的未利用地面积所占比重较大,后备土地资源丰富;(2)多目标优化结果显示,耕地、林地、水域和建设用地面积呈现增加的趋势;草地面积基本保持不变;未利用地面积大幅度下降;(3)土地利用生态安全格局显示,耕地面积增加,主要分布在水分条件较好的河流、湖泊和水库等的周边地区以及城镇和乡村居民点周围;林地面积大幅度增加,主要分布在达拉特旗北部和准格尔旗东部;草地略有增加,广泛分布于库布齐沙漠和毛乌素沙地以外的地区;建设用地增加面积主要来自于重点发展城镇的扩展和规划的重点矿产资源开采区;未利用地大幅度减少,主要集中在杭锦旗境内的库布齐沙漠以及乌审旗和鄂托克旗境内的毛乌素沙地。研究结果对鄂尔多斯市土地资源管理和生态安全建设具有重要指导意义。     

不同干扰背景下景观指数与物种多样性的多尺度效应——以巩义市为例

以黄河中下游山地丘陵区的巩义市为研究区,采用典型样地法对灌草丛、人工林和农田边缘3种不同干扰背景下的自然、半自然生境内的植物进行调查。基于景观生态学原理,在地理信息系统技术支持下,借助于Fragstatta3.3软件,以调查样地为中心,计算了150、250、500、750、1000、1250、1500m不同半径缓冲区内表征景观形状(Edge and patch shape)、边缘对照(Edge contrast)、相似度和邻近度(Proximity and similarity)、景观多样性(Diversity)、基质(Texture)、斑块大小和密度(Patch size and patch density)共6类52个指数,运用冗余分析(RDA)筛选出不同尺度下对该区农业景观中植物多样性有显著影响的景观指数。结果表明:不同尺度,景观指数对物种多样性的影响变化显著。灌草丛生境,在500—750m范围内,SHAPE_AM指数和PARA_AM指数能够很好的解释物种多样性,解释量为33.6%;人工林生境,SHAPE_AM指数、AREA_CV指数、SIMI指数和PAFRAC指数在1000—1250m范围内对物种多样性的解释量达到48.1%;农田边缘生境,GYRATE_CV指数、ENN_CV指数、PARA_MN指数和FRAC_AM指数在750—1250m范围内对物种多样性影响显著,解释量为32%。其中,辛普森多样性指数(SIDI)与灌草丛物种多样性在750—1250m范围内作用显著,ENN_CV指数仅对农田边缘物种多样性影响较大。景观指数对物种多样性的影响具有尺度依赖性,未来应全面综合探讨这些指数的尺度效应及在景观生态学中的应用。     

南京农业大学微生物学虚拟仿真实验教学模式的探索

借助虚拟仿真技术构建的虚实结合的虚拟仿真实验,是提高学生实践动手能力的有力补充和有效途径。本文通过对微生物学实验教学现状的分析,探讨南京农业大学微生物学虚拟仿真实验教学模式建设的意义,重点阐述建设思路、建设方案及教学特点。该仿真实验教学体系主要从基础微生物学和应用微生物学两大模块进行构建,同时将本校的污水生物处理技术、食用菌资源调查与利用等科研成果转化为教学资源,以丰富实验教学内容。     

典型矿区植被覆盖度时空分布特征及影响因素

植被状况可以直接或间接地反映采煤对生态环境的影响。以长河井工煤矿、离柳井工煤矿、平朔露天煤矿3个典型矿区为研究区域。以Landsat数据为数据源,基于地形调节植被指数的像元二分模型提取植被覆盖度;采用趋势分析、线性回归斜率、稳定性分析方法,分析了3个典型矿区2001-2016年植被覆盖度的时空变化特征;运用"以时间换空间"的方法,采用相关分析方法对植被覆盖度变化的自然影响因素进行了分析。结果表明：（1）近16年3个典型矿区植被覆盖度呈增加趋势,长河、离柳、平朔矿区的增长速率分别为0.09%/10 a、0.10%/10 a、0.08%/10 a（P > 0.05）。（2）空间上,长河、离柳、平朔矿区植被覆盖度变化不明显比例分别占到66.63%,59.90%,62.25%,呈增加趋势的比例仅分别占28.14%、32.55%、27.81%,而呈减少趋势的比例分别占到5.23%、7.55%、9.94%。长河矿区明显改善的区域位于自然植被和耕作区的北部和东北部,离柳矿区明显改善的区域位于以低植被覆盖度为主的北部,平朔矿区明显改善的区域位于复垦的中西部。（3）不区分植被类型时,3个矿区的植被覆盖度变化与高程、高程与温度的交互作用表现出显著相关性（P < 0.01）,与各自然因素的相关性总体表现为长河 > 离柳 > 平朔矿区;区分植被类型时,草地与坡度的相关性不显著（P > 0.05）,与降雨量、高程存在显著正相关（P < 0.05）;灌木林与温度相关性不显著,与高程和降雨量的交互作用存在显著正相关;旱地与高程、高程与温度的交互作用存在显著相关性;疏林地与坡向、降雨量与坡向坡度的交互作用均没有表现出相关性;有林地与高程降雨量的交互作用表现出显著正相关性。探讨不同植被类型对自然因素的响应,可为矿区植被结构的选择,矿区复垦提供参考依据。     

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases