A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery

To further enhance the intensity of deep tumor drug delivery and integrate a combined therapy, we herein report on a core-shell nanocarrier that could simultaneously overcome the double barriers of the extracellular matrix (ECM) and multiple layers of tumor cells (MLTC). A pH-triggered reversible swelling-shrinking core and an MMP2 (matrix metallopeptidase 2) degradable shell were developed to encapsulate chemotherapeutics and macroautophagy/autophagy inhibitors, respectively. MMP2 degraded the shell, which was followed by the autophagy inhibitors' release. The exposed core could diffuse along the pore within the ECM to deliver chemotherapeutics into deep tumors, and it was able to swell in lysosomes and shrink back in the cytoplasm or ECM. The swelling of the core resulted in the rapid release of chemotherapeutics to kill autophagy-inhibited cells. After leaving the dead cells, the shrinking core could act on neighboring cells that were closer to the center of the tumor. The core thus could also cross MLTC layer by layer to deliver chemotherapeutics into the deep tumor.     

Erosion reduces soil microbial diversity,network complexity and multifunctionality

While soil erosion drives land degradation, the impact of erosion on soil microbial communities and multiple soil functions remains unclear. This hinders our ability to assess the true impact of erosion on soil ecosystem services and our ability to restore eroded environments. Here we examined the effect of erosion on microbial communities at two sites with contrasting soil texture and climates. Eroded plots had lower microbial network complexity, fewer microbial taxa, and fewer associations among microbial taxa, relative to non-eroded plots. Soil erosion also shifted microbial community composition, with decreased relative abundances of dominant phyla such as Proteobacteria, Bacteroidetes, and Gemmatimonadetes. In contrast, erosion led to an increase in the relative abundances of some bacterial families involved in N cycling, such as Acetobacteraceae and Beijerinckiaceae. Changes in microbiota characteristics were strongly related with erosion-induced changes in soil multifunctionality. Together, these results demonstrate that soil erosion has a significant negative impact on soil microbial diversity and functionality.Subject terms: Soil microbiology, Microbial ecology     

Insight for Immunotherapy of HCMV Infection

Human cytomegalovirus (HCMV), a ubiquitous in humans, has a high prevalence rate. Young people are susceptible to HCMV infection in developing countries, while older individuals are more susceptible in developed countries. Most patients have no obvious symptoms from the primary infection. Studies have indicated that the virus has gradually adapted to the host immune system. Therefore, the control of HCMV infection requires strong immune modulation. With the recent advances in immunotherapy, its application to HCMV infections is receiving increasing attention. Here, we discuss the immune response to HCMV infection, the immune escape mechanism, and the different roles that HCMV plays in various types of immunotherapy, including vaccines, adoptive cell therapy, checkpoint blockade therapy, and targeted antibodies.     

黄孢原毛平革菌抗营养阻遏产漆酶诱变育种及其产酶特性

【目的】筛选能抗营养阻遏产漆酶的黄孢原毛平革菌,论证其产漆酶的确定性及抗营养阻遏产木质素酶的可行性,为白腐菌产酶代谢调控、木质素降解机理的研究奠定基础。【方法】利用重复紫外诱变法,以愈创木酚富氮鉴别培养基筛选目标菌株;比较不同营养条件下菌体生长与产酶动力学差异研究产酶营养调控机理;通过热处理、排除锰离子和加入过氧化氢酶等不同措施论证黄孢原平毛平革菌能否产生漆酶。【结果】3种不同方法均证实选育到的pcR5305和pcR5324菌株在限氮与富氮条件下均能产生漆酶,pcR5305和pcR5324在限氮条件下产漆酶分别达到203.5、187.6 U/L;在富氮条件下为220.6、183.9 U/L,而原菌株pc530在两种条件下都基本不产生漆酶。二菌株产漆酶调控方式不同,pcR5305漆酶产生与菌体生长同步,而pcR5324漆酶产生却受营养氮阻遏。二菌株同时具有抗营养阻遏高产木质素过氧化物酶(LiP)和锰过氧化物酶(MnP)(分别为LiP 1343.2、MnP 252.2 U/L;LiP 1169.5、MnP 172.4 U/L)的能力。【结论】筛选到的黄孢原毛平革菌变异菌株能产漆酶,同时表现了抗营养阻遏产漆酶、木质素过氧化物酶和锰过氧化物酶的能力,具有重要的生产应用与理论研究价值,为白腐菌产酶代谢调控机理研究提供了原始菌株并奠定了良好的基础。     

软腐白菜细菌群落结构多样性与生长环境的相关性

[目的]通过对比分析不同生境白菜软腐病变组织与根系土壤相关细菌的群落结构,探讨白菜软腐细菌种群的多样性,以及与生境土壤细菌种群的相关性.[方法]样品采自河南省2个不同生态型白菜田,以成熟白菜软腐组织及病株根系土壤为目标,利用模拟原环境的培养基成分和条件,对样品中的细菌进行高通量分离培养和细胞16S rRNA基因序列比对分析,获得各样品细菌种群结构及其丰度,进而对各样品的优势菌群进行对比分析.[结果]两种不同生境白菜软腐组织细菌总量M05T为4.0×l0s cell/g、Q2T为1.2×1011 cell/g,分别获得纯菌56株和85株.M05T优势菌为萎蔫短小杆菌萎蔫亚种(Curtobacterium flaccunfaciens pv.Flaccumfaciens);Q2T优势菌为假单胞菌(Pseudomonas spp.)(柄木槿假单胞菌(P.hibiscicola)、台湾假单胞菌(P.taiwanensis)、托木尔假单胞菌(P.tuomuerensis)、莫塞尔假单胞菌(P.mosselii)).根系土壤细菌总量M05S为2.7 × 105 cell/g、Q2S为6.2 × 107 cell/g,分别获得纯菌36株和70株.M05S优势菌为巨大芽胞杆菌(Bacillus megatherium);Q2S优势菌为假单胞菌(Pseudomonas spp.)(香鱼假单胞菌(P.plecoglossicida)、栖木槿假单胞菌(P.hibiscicola)、类黄色假单胞菌(P.parafulva)、蒙氏假单胞菌(P.monteilii)、膝形假单胞菌(P.geniculata)).[结论]依据不同生境的白菜软腐组织和根系土壤细菌群落结构对比分析,认为白菜软腐菌可能具有多样性和多种致病来源,本研究为软腐病多种防治措施的制定提供基础研究和菌种资源.     

miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells

It has become increasingly clear that microRNAs play an important role in many human diseases including cancer. Here, we show that expression of miR-21 in HEK293 and several colorectal cancer cells was found inversely correlated with ras homolog gene family, member B (RhoB) expression. miR-21 expression significantly suppressed RhoB 3' UTR luciferase-reporter activity, but the inhibitory effect was lost when the putative target sites were mutated. Exogenous miR-21 over-expression mimicked the effect of RhoB knockdown in promoting proliferation and invasion and inhibiting apoptosis, whereas anti-miR-21 or RhoB expression yielded opposite effects, in colorectal cancer cells. These results suggest that miR-21 is a regulator of RhoB expression and RhoB could be a useful target in exploring the potential therapeutic benefits of miR-21 mediated tumor cell behaviors in colorectal cancer.