Twenty-eight bacterial and Br transport experiments were performed in the field to determine the effects of physical and chemical heterogeneity of the aquifer sediment. The experiments were performed using groundwater from two field locations to examine the effects of groundwater chemistry on transport. Groundwater was extracted from multilevel samplers and pumped through 7-cm-long columns of intact sediment or repacked sieved and coated or uncoated sediment from the underlying aquifer. Two bacterial strains, Comamonas sp. DA001 and Paenibacillus polymyxa FER-02, were injected along with Br into the influent end of columns to examine the effect of cell morphology and cell surface properties on bacterial transport. The effects of column sediment grain size and mineral coatings coupled with groundwater geochemistry were also investigated. Significant irreversible attachment of DA001 was observed in the Fe oxyhydroxide-coated columns, but only in the suboxic groundwater where the concentrations of dissolved organic carbon (DOC) were ca. 1 ppm. In the oxic groundwater where DOC was ca. 8 ppm, little attachment of DA001 to the Fe oxyhydroxide-coated columns was observed. This indicates that DOC can significantly reduce bacterial attachment due electrostatic interactions. The larger and more negatively charged FER-02 displayed increasing attachment with decreasing grain size regardless of DOC concentration, and modeling of FER-02 attachment revealed that the presence of Fe and Al coatings on the sediment also promoted attachment. Finally, the presence of Al coatings and Al containing minerals appeared to significantly retard the Br tracer regardless of the concentration of DOC. These findings suggest that DOC in shallow oxic groundwater aquifers can significantly enhance the transport of bacteria by reducing attachment to Fe, Mn and Al oxyhydroxides. This effect appears to be profound for weakly and strongly charged hydrophilic bacteria and may contribute to differences in observations between laboratory experiments versus field-scale investigations particularly if the groundwater pH remains subneutral and Fe oxyhydroxide phases exist. These observation validate the novel approach taken in the experiments outlined here of performing laboratory-scale experiments on site to facilitate the use of fresh groundwater and thus be more representative of in situ groundwater conditions.

2002-05-01·Applied and Environmental Microbiology2区 · 生物学

Simultaneous Transport of Two Bacterial Strains in Intact Cores from Oyster, Virginia: Biological Effects and Numerical Modeling

2区 · 生物学

Article

作者: Rothmel, Randi ; Dunlap, Robb ; Fletcher, Madilyn ; Dong, Hailiang ; Fuller, Mark E. ; DeFlaun, Mary F. ; Onstott, Tullis C. ; Streger, Sheryl H.

ABSTRACT The transport characteristics of two adhesion-deficient, indigenous groundwater strains, Comamonas sp. strain DA001 and Erwinia herbicola OYS2-A, were studied by using intact sediment cores (7 by 50 cm) from Oyster, Va. Both strains are gram-negative rods (1.10 by 0.56 and 1.56 by 0.46 μm, respectively) with strongly hydrophilic membranes and a slightly negative surface charge. The two strains exhibited markedly different behaviors when they were transported through granular porous sediment. To eliminate any effects of physical and chemical heterogeneity on bacterial transport and thus isolate the biological effect, the two strains were simultaneously injected into the same core. DA001 cells were metabolically labeled with 35 S and tagged with a vital fluorescent stain, while OYS2-A cells were metabolically labeled with 14 C. The fast decay of 35 S allowed deconvolution of the two isotopes (and therefore the two strains). Dramatic differences in the transport behaviors were observed. The breakthrough of DA001 and the breakthrough of OYS2-A both occurred before the breakthrough of a conservative tracer (termed differential advection), with effluent recoveries of 55 and 30%, respectively. The retained bacterial concentration of OYS2-A in the sediment was twofold higher than that of DA001. Among the cell properties analyzed, the statistically significant differences between the two strains were cell length and diameter. The shorter, larger-diameter DA001 cells displayed a higher effluent recovery than the longer, smaller-diameter OYS2-A cells. CXTFIT modeling results indicated that compared to the DA001 cells, the OYS2-A cells experienced lower pore velocity, higher porosity, a higher attachment rate, and a lower detachment rate. All these factors may contribute to the observed differences in transport.

2002-03-01·Environmental Science & Technology1区 · 环境科学与生态学

Relative Dominance of Physical versus Chemical Effects on the Transport of Adhesion-Deficient Bacteria in Intact Cores from South Oyster, Virginia

1区 · 环境科学与生态学

Article

作者: Rothmel, Randi K. ; DeFlaun, Mary F. ; Mailloux, Brian J. ; Onstott, T. C. ; Streger, Sheryl H. ; Dong, Hailiang ; Scheibe, Timothy D. ; Fuller, Mark E.

Bacterial transport experiments were conducted using intact sediment cores collected from sites on the Delmarva Peninsula near South Oyster, VA, to delineate the relative importance of physical and chemical heterogeneity in controlling transport of an adhesion-deficient bacterial strain. Electron microscopy revealed that the sediments consisted of quartz and feldspar with a variable amount of clay and iron and aluminum hydroxide coatings on the grains. A nonmotile, gram-negative indigenous groundwater strain, designated as Comamonas sp. DA001, was injected into the cores along with a conservative tracer bromide (Br). DA001 cells were 1.2 x 0.6 microm in size with a hydrophilic surface and a slightly negative surface charge. Bacterial breakthrough preceded that of Br. This differential advection phenomenon can be accounted for by reduction of the effective porosity for the bacteria relative to Br. The distribution of cells remaining in the core as determined by scintillation counting and phosphor imaging techniques was variable, ranging from nearly uniform concentrations throughout the core to exponentially decreasing concentrations with distance from the point of injection. The fraction of bacterial retention in the core was positively correlated with the abundance of the metal hydroxides and negatively correlated with grain size. Because grain size was inversely correlated with the abundance of the metal hydroxide coatings, it was necessary to separate the effects of grain size and mineralogy. The fraction of the bacterial retention accounting for the effect of grain size, the collision efficiency, exhibited no correlation with the abundance of the metal hydroxides, indicating that the bacterial retention was primarily controlled by grain size. Reasons for the lack of influence of mineralogy on bacterial transport include (i) the slightly negatively charged bacterial surfaces; (ii) an insufficient heterogeneity of sediment surface properties; and (iii) the masking of the positive charge of the metal hydroxide surfaces by adsorbed organic carbon (up to 1180 ppm). This study demonstrates that the laboratory-based bacterial transport experiments are effective in delineating physical versus chemical controlling factors and provide an important link to field-based bacterial transport studies.

项与 DA-001 相关的新闻（医药）

2024-06-27

·创鉴汇

上半年23家上海创新药公司获融资！

▎药明康德内容团队编辑上海高度重视生物医药科技创新和产业发展，加快打造全球生物医药研发经济和产业化高地。2024上半年，至少86家中国创新药公司完成了新一轮融资，上海公司包揽了其中的1/4以上。据不完全统计，上半年23家上海创新药公司获融资，已披露融资总额超33.5亿元。值得关注的亮点包括：亿元或以上融资事件数超六成：在已披露金额的16起融资事件中，10起为亿元或以上的大额融资，潜在最高融资金额来自箕星药业完成的1.62亿美元D轮融资。细胞与基因疗法（CGT）为热门研发方向：至少7家公司正在推进细胞与基因疗法研发，占到总数的三分之一以上，如先博生物、跃赛生物、恒瑞源正、篆码生物等。此外，抗体偶联药物、双特异性抗体、核酸药物也受到了较多关注，均有至少3-4家公司正在开发。抗肿瘤持续受到关注：超60%的公司布局了抗肿瘤药物研发，如德昇济医药、辐联科技等；罕见病、血液系统疾病也受到了较为广泛的关注，均有约三成的公司正在推进相关领域的管线开发。近两年成立新锐公司崭露头角：5家获融资公司成立于2022年以后，包括星核迪赛、星联肽、篆码生物、迦进生物、灵识质源，细胞与基因疗法、偶联药物是这些公司看重的研发方向，均有两家公司涉及。箕星药业：心血管疾病及眼科等新药研发公司 1月6日消息，箕星药业（JIXING）宣布完成1.62亿美元D轮融资，由拜耳（Bayer）、RTW投资公司分别以3500万美元和1.27亿美元对其进行股权投资。通过此次合作，拜耳将获得箕星药业在心血管和眼科领域产品线商业化权益的优先谈判权。箕星药业是一家总部位于上海的生物医药公司，由RTW公司于2019年投资创立，致力于通过开发和商业化独特创新的治疗药物，应对心血管和眼科等疾病领域尚未满足的医疗需求。 ▲箕星药业心血管研发管线（图片来源：公司官网）据官网介绍，箕星药业目前有9个临床后期阶段在研产品和1个临床前阶段在研产品，主要聚焦心血管、眼科两个板块。其中，进展较快的aficamten是一种在研的选择性小分子心肌肌球蛋白抑制剂。3月，中国国家药品监督管理局药品审评中心（CDE）已批准aficamten的一项中国3期临床试验申请，针对的适应症为用于治疗症状性非梗阻性肥厚型心肌病（nHCM）患者。据新闻稿，本次获批的研究是该药在中国开展的第四个3期临床试验项目。在眼科板块进展较快的伐尼克兰鼻喷雾剂是一种高选择性的胆碱能受体激动剂，经美国FDA批准用于治疗干眼的症状和体征。德昇济医药：肿瘤免疫疾病创新药研发公司 4月8日，德昇济医药宣布完成6200万美元A+轮融资。本轮融资资金将用于加速德昇济医药产品管线在临床前和临床阶段的开发，特别是推动首款产品D3S-001的全球临床试验。德昇济医药成立于2020年，在上海设有办公地点，是一家面向全球、临床阶段的生物技术公司，专注于肿瘤及免疫精准治疗药物的研发及商业化。该公司充分利用对临床的洞察和生物标志物策略来指导药物发现和开发，旨在为患者创造临床意义重大的创新疗法。 ▲德昇济医药研发管线（图片来源：公司官网）德昇济医药已经建立了多条肿瘤项目药物管线，这些项目都具有“first-in-class"或“best-in-class”的潜力，并携带靶向免疫通路或肿瘤驱动突变的基础特性。其中进展较快的D3S-001是新一代小分子KRAS G12C抑制剂。目前，D3S-001正在进行全球2期临床开发，适应症包括非小细胞肺癌、结直肠癌和胰腺癌。辐联科技：放射性药物开发公司 1月4日，辐联科技（Full-Life Technologies）宣布完成4730万美元的B轮股权融资。本轮融资资金将用于帮助公司快速推进其放射性药物管线的开发和药物生产能力的建设，并优化其专有发现平台UniRDC。该平台旨在加速及流程化放射性偶联药物的发现过程。辐联科技是一家成立于2021年的放射性治疗公司，中国办事处位于上海自贸区，致力于打造拥有放射性药物研发、生产和商业化的全产业链核药公司以造福全球患者，并计划通过针对未来治疗方法的创新研究来解决目前影响放射性药物研发的核心问题。 ▲辐联科技研发管线（图片来源：公司官网） 5月30日，辐联科技宣布其PSMA靶向放射性药物225Ac-FL-020已获得美国FDA新药临床试验（IND）的批准，用于治疗转移性去势抵抗性前列腺癌（mCRPC）。225Ac-FL-020是创新型下一代PSMA放射配体疗法的候选药物，其靶向载体FL-020运用了辐联科技专有的Clear-X连接子技术研发而成，该技术能显著增强药物在肿瘤部位的摄取效率，同时确保快速的全身清除。此外，6月11日，辐联科技在2024年SNMMI（核医学和分子影像学会）年会上以口头报告形式公布了其NTSR1靶向放射性核素偶联药物（RDC）项目FL-091的临床前数据研究成果。这一放射性配体载体展现出了良好的生物分布特性和优异的抗肿瘤活性。先博生物：细胞疗法研发公司 3月11日消息，先博生物宣布完成2亿元人民币A+轮融资。先博生物成立于2019年，中国总部位于上海浦东新区，是一家处于临床开发阶段的细胞治疗生物技术公司。以血液瘤和实体瘤临床需求为目标，该公司专注于开发创新型免疫细胞疗法，目前的研发领域涵盖CAR-NK细胞疗法、多靶向CAR-T细胞疗法，以及通过合作布局基于环状mRNA以及定向递送平台的下一代通用型体内细胞治疗产品。 ▲先博生物研发管线（图片来源：公司官网）据先博生物公开资料，该公司首个通用型CAR-NK产品管线SNC103已经在研究者发起的临床研究（IIT）阶段取得了积极结果，并于今年2月在中国获批临床，拟开发治疗中重度难治性系统性红斑狼疮。SNC103是一款靶向CD19的嵌合抗原受体基因修饰的NK细胞注射液。另一款携带两个CAR分子的双CAR-T细胞疗法SNC109也已经在中国获批临床，并被美国FDA授予孤儿药资格，用于治疗恶性胶质瘤。这款CAR-T产品细胞表面携带两个CAR分子，分别靶向在胶质母细胞瘤中表达的IL13Rα2和HER2。跃赛生物：多能干细胞药物研发公司 4月3日，跃赛生物宣布完成超亿元A轮融资。此次融资资金将用于加速推进公司的在研管线与临床试验进程，进一步深化创新细胞治疗药物的规模化开发和产业化建设。跃赛生物于2021年成立于上海，致力于开发新一代基于人多能干细胞技术的细胞治疗药物，其在研管线覆盖了帕金森病和其他神经退行性疾病。近年来，跃赛生物取得了重大进展，预计在2024年完成IND临床试验申请，并计划于2025年初开始试验入组。该公司的多项研发成果已发表于Nature Methods、Cell Stem Cell等国际权威学术期刊。 ▲跃赛生物研发管线（图片来源：公司官网）根据跃赛生物官网资料，该公司现已拥有5条研发管线，其中进展较快的UX-DA001针对帕金森病。跃赛生物将干细胞技术与SISBAR谱系示踪技术及HiDAP神经元分化技术相结合，将iPSC分化为中脑多巴胺能神经前体细胞，用以补充患者脑内丢失的多巴胺能神经元。临床前研究显示，DA001产品能有效改善PD模型动物运动障碍，增加纹状体多巴胺浓度，并且移植细胞可与宿主产生稳定的功能性连接。熙源安健：止痛药研发公司 4月23日，熙源安健宣布完成超亿元Pre-A和Pre-A+融资。本轮所融资金将用于其产品管线在临床前和临床阶段的开发，特别是加速其自主研发并进入临床的CGRP类小分子药物BR005项目的临床试验进度。熙源安健成立于2021年，官网地址位于上海，专注于开发针对严重慢性疼痛病症的创新型、高特异性的镇痛疗法，尤其重视解决头面部疼痛、肌肉骨骼疼痛和神经性疼痛等临床长期未满足需求。该公司的愿景是为全球众多饱受慢痛折磨的患者提供安全、有效、便捷的疼痛管理解决方案。 ▲熙源安健研发管线（图片来源：公司官网）熙源安健目前已有两款药物进入临床阶段。其中，BR005是一款小分子CGRP受体拮抗剂，已经在中国获批临床，拟用于治疗成人有先兆或无先兆急性偏头痛，目前1期临床研究已完成首例受试者入组。另一款在研产品BR01T为一款TrkA抗体，拟开发用于治疗慢性下腰痛。该产品此前已经在美国完成1期临床研究首例患者的给药，针对慢性下腰痛患者。星核迪赛：mRNA药物开发公司 4月30日，星核迪赛宣布完成近亿元天使轮融资。本轮融资将用于DSL101和DSL201等核心管线的持续推进、继续开发新型脂质化合物及LNP递送系统，进一步拓展核酸药物管线布局等。星核迪赛成立于2022年，官网地址位于上海浦东新区，由复健资本新药创新基金孵化设立，主要聚焦药物递送系统研发和重大临床需求mRNA药物的开发，致力于成为集研发与生产为一体的核酸创新药公司。 ▲星核迪赛研发管线（图片来源：公司官网）星核迪赛创始科学家占昌友教授表示，星核迪赛团队拥有丰富的LNP等复杂制剂药物开发和项目管理经验，支撑在研管线的迅速推进。公司在成立不到两年的时间，已经开发出多种特色的LNP递送系统和可电离脂质候选化合物，完成多条管线的立项，其中DSL101和DSL201两条管线目前已启动研究者发起的临床研究（IIT）研究和IND申报准备工作。星联肽：蛋白偶联药物研发公司 1月，星联肽宣布完成9000万元Pre-A轮融资。本轮融资资金将用于：多肽偶联药物SC-101和SC-102的临床试验研究；纳米抗体偶联药物自研平台的搭建及相关产品的开发；星联肽团队的完善和公司的日常运营。星联肽成立于2022年2月，官网地址位于上海浦东新区，致力于开发新型小型化偶联药物，包括多肽偶联药物（PDC）和纳米抗体偶联药物（NDC）。通过采用合作开发和自主研发相结合的模式，该公司已建立了具有差异化特点的研发管线，目前已启动5款候选药物的开发。星联肽的首款产品SC-101是靶向Nectin-4的PDC，由高表达的hNectin-4蛋白的多肽和微管蛋白抑制剂经连接子偶联而成，2024年2月已完成患者首例给药。该公司开发的另一款PDC产品SC-102已于2023年底提交了Pre-IND申请。读者们请星标⭐创鉴汇，第一时间收到推送免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

临床3期引进/卖出基因疗法

100 项与 DA-001 相关的药物交易

登录后查看更多信息