Prescribing engagement in environmental risk assessment for gene drive technology

Gene drive technology is a nascent biotechnology with the potential to purposefully alter or eliminate a species. There have been broad calls for engagement to inform gene drive governance. Over the past seven years, the gene drive community has been developing risk assessment guidelines to determine what form future gene drive risk assessments take, including whether and how they involve engagement. To explore who is developing these guidelines and how engagement in risk assessment is being prescribed, we conduct a document analysis of gene drive risk assessment guideline documents from 2014 to 2020. We found that a narrow set of organizations have developed 10 key guideline documents and that with only one exception the documents prescribe a narrow, vague, or completely absent role for engagement in gene drive risk assessment. Without substantively prescribed engagement in guidelines, the relevance, rigor, and trustworthiness of gene drive risk assessment and governance will suffer.     

阳和平喘颗粒早期和晚期干预对哮喘大鼠支气管肺泡灌洗液中白细胞介素-5和白细胞介素-9的影响

目的 从细胞因子水平研究阳和平喘颗粒防治支气管哮喘的机制。方法 将84只清洁级SD大鼠随机分为正常组，模型组，地塞米松组，阳和平喘颗粒早期干预低剂量组、早期干预高剂量组、晚期干预低剂量组、晚期干预高剂量组，采用卵清白蛋白多点长期致敏及激发的方法复制大鼠哮喘模型。给予相应药物分阶段干预，观察哮喘大鼠肺组织病理形态变化，采用ELISA法检测支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中（interleukin-5, IL-5）和（interleukin-9, IL-9）水平。结果 各给药组大鼠气管壁黏膜与肺周围血管组织的炎性细胞浸润及气管壁增厚均较模型组明显减轻。阳和平喘颗粒早期用药降低BALF中IL-5和IL-9的作用优于晚期用药，高剂量阳和平喘颗粒降低BALF中IL-5和IL-9的作用优于低剂量，阳和平喘颗粒低剂量晚期用药降低BALF中IL-5和IL-9的作用与地塞米松相当。结论 阳和平喘颗粒防治支气管哮喘的机制与其降低BALF中IL-5、IL-9水平有关，早期用药的效应优于晚期用药，其效应具有一定的剂量依赖性。     

基于网络药理学和分子对接技术探究小柴胡汤治疗三阴性乳腺癌的作用机制

目的 通过生物信息学分析和整合药物代谢动力学数据进行多重药物靶点预测，探究小柴胡汤治疗三阴性乳腺癌（triple negative breast cancer，TNBC）的作用机制。方法 基于药理学数据库获取小柴胡汤的活性成分与对应靶点；采用加权基因共表达网络分析方法识别乳腺癌高通量测序数据中肿瘤发生发展的关键基因；采用GO功能与KEGG通路富集分析进行生物功能与通路注释；通过Cytoscape软件进行核心基因鉴定；利用分子对接方法模拟关键生物标志物与小柴胡汤核心活性成分的对接模式。结果 在对小柴胡汤进行数据挖掘后获得242个有效成分和265个对应靶点，通过加权分析方法得到乳腺癌密切相关的563个疾病关键靶点，小柴胡汤与TNBC共有13个交集靶点。小柴胡汤成分靶点网络构建得到槲皮素、山柰酚、异鼠李亭素、木犀草素、豆甾醇、β-豆甾醇、牵牛花色素等主要成分。PPI网络构建后通过筛选得到3个核心靶点（CCNA2、CCNB1、CHEK1）与2个关键化学成分（槲皮素、山柰酚）。GO富集获得15个生物过程、45个细胞组分、16个分子功能，其中主要与细胞器裂变和细胞核分裂等细胞增殖过程，浓缩染色体和中心区核染色体，单链DNA结合ATP依赖活性等相关。KEGG通路富集得到了37条通路，主要富集在精氨酸等代谢通路上。分子对接模拟显示核心蛋白靶点与重要活性成分具有良好的结合活性。结论 小柴胡汤主要通过CCNA2、CCNB1、CHEK1等靶点，槲皮素、山柰酚等主要活性成分及细胞调亡、成纤维细胞形成和肿瘤细胞增殖及炎症进程达到干预TNBC的作用。     

四物汤对血管性痴呆大鼠的神经保护作用及其机制研究

目的 探讨四物汤对血管性痴呆（vascular dementia，VD）大鼠的保护作用及其机制。方法 将SD大鼠随机分为假手术组，模型组，四物汤高剂量（6 g/kg）、低剂量（3 g/kg）组，尼莫地平组（20 mg/kg），每组12只。采用大脑中动脉阻塞再灌注法复制大鼠VD模型，术后连续给予相应药物14 d。采用水迷宫实验观察VD大鼠学习能力和记忆能力；酶联免疫吸附法测定海马组织中乙酰胆碱酯酶（acetylcholinesterase，AChE）、5- 羟色胺（5- hydroxy tryptamine，5- HT）、内皮素- 1（endothelin- 1，ET- 1）、血管内皮生长因子（vascular endothelial growth factor，VEGF）的含量。腹主动脉取血检测血液流变学指标。苏木精- 伊红染色观察海马CA1区神经细胞形态学变化。结果 与模型组比较，四物汤高剂量组大鼠逃避潜伏期明显缩短（P<0.05），在目标象限距离百分比显著增加（P<0.05），海马AChE、ET- 1含量显著降低（P<0.05），5- HT、VEGF含量显著升高（P<0.05），全血黏度、血浆黏度和红细胞聚集指数显著降低（P<0.05）。四物汤高、低剂量组比较，仅血浆黏度和红细胞聚集指数的差异具有统计学意义（P<0.05）。与模型组比较，四物汤组海马CA1区锥体细胞缺失减轻，神经纤维排列整齐，仅少数细胞核固缩。结论 四物汤对VD具有一定的改善作用，其机制与改善神经递质，调节海马ET- 1、VEGF含量，改善血流状态有关。     

丹蛭降糖胶囊对糖尿病大鼠血清TNF-α和CXCL-5的影响

目的 观察丹蛭降糖胶囊对糖尿病大鼠血清肿瘤坏死因子-α（tumor necrosis factor alpha， TNF-α）和趋化因子（C-X-C基序）配基5（chemokine (C-X-C motif) ligand 5，CXCL-5）表达的影响，探究其降糖作用机制。方法 将健康雄性SD大鼠随机分为正常对照组，模型组，吡格列酮组，丹蛭降糖胶囊高、低剂量组。采用链尿佐菌素单次腹腔注射法复制糖尿病模型，采用双抗体夹心法测定大鼠血清TNF-α、CXCL-5水平。结果 与模型组比较，吡格列酮组和丹蛭降糖胶囊高、低剂量组TNF-α、CXCL-5水平显著降低（P＜0.01），3个给药组TNF-α、CXCL-5比较，差异均无统计学意义（P>0.05）。与模型复制后0周末比较，2、4、8周末，吡格列酮组和丹蛭降糖胶囊高、低剂量组血糖水平均显著降低（P<0.01）。2、4、8周末，与模型组比较，吡格列酮组及丹蛭降糖胶囊高、低剂量组血糖水平均显著降低（P＜0.01），但3个给药组之间血糖水平比较，差异均无统计学意义（P>0.05）。Pearson相关分析显示，8周末血糖水平与TNF-α、CXCL-5均呈正相关（P<0.01）。结论 丹蛭降糖胶囊降低糖尿病大鼠血糖的机制与其降低血清TNF-α、CXCL-5水平有关。     

Lipidic compounds found in soils surrounding human decomposing bodies and its use in forensic investigations – A narrative review

Following decomposition of a human body, a variety of decomposition products, such as lipids, are released into the surrounding environment, e.g. soils. The long-lasting preservation in soils and their high diagnostic potential have been neglected in forensic research. Furthermore, little is known about the preservation, chemical transformation, or degradation of those human derived lipids in soils. To date, several studies identified various lipids such as long-chain free fatty acids and steroids in soils that contained decomposition fluids. Those lipids are preserved in soils over time and could serve as markers of human decomposition in forensic investigations, e.g. for estimating the post-mortem interval or identifying the burial location of a human body. Therefore, this review focuses on the current literature regarding fatty acid and steroid that have been detected in soils and associated with human body decomposition. After a short introduction about human decomposition processes, this review summarises fatty acid and steroid analysis applied in current case studies and studies related to taphonomic research. This review provides an overview of the available studies that have used fatty acids and steroids as identifiers of human decomposition fluid in soils in a forensic context and discusses the potential for developing this innovative field of research with direct application in a forensic context.     

Informing regional taphonomy research using retrospective forensic anthropology cases in the Western Cape,South Africa

The post-mortem interval (PMI) is important in death investigations as it can assist in reconstructing the context of the case and the identification of the unknown individual. However, in some instances the PMI is challenging to estimate due to the absence of regional taphonomy standards. To conduct accurate and locally relevant forensic taphonomy research, investigators require insight into the regional hotspot recovery areas. Thus, forensic cases examined by the Forensic Anthropology Cape Town (FACT) in the Western Cape (WC) province of South Africa between 2006 and 2018 (n = 172 cases; n = 174 individuals) were retrospectively reviewed. In our study, a considerable number of individuals did not have the PMI estimations (31 %; 54/174) and the ability to estimate a PMI was significantly associated with skeletal completeness, unburnt remains, absence of clothing and the absence of entomological evidence (p < 0.05 for each). Significantly fewer cases had the PMI estimated after FACT was formalised in 2014 (p < 0.0001). One third of cases with PMI estimations were made with large open-ended ranges, making them less informative. Factors significantly associated with these broad PMI ranges were fragmented remains, absence of clothing and absence of entomological evidence (p < 0.05 for each). Most decedents (51 %; 87/174) were discovered in police precincts from high crime areas, yet a considerable number (47 %; 81/174) were also found in low crime and sparsely populated areas regularly used for recreational activities. Common sites of body discovery were vegetated areas (23 %; 40/174), followed by the roadside (15 %; 29/174), aquatic environments (11 %; 20/174) and farms (11 %; 19/174). Decedents were discovered exposed (35 %; 62/174), covered with items such as bedding or shrubs (14 %; 25/174) or buried (10 %; 17/174). Our data highlight gaps in forensic taphonomy studies and clearly informs what regional research is needed. Overall, our study demonstrates how forensic case information can inform regional forensic taphonomy studies to locate common areas and contexts for the discovery of decomposed bodies and encourages similar studies in other areas of the world.