A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity

Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries.     

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a–b and 11a–b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I₂/ImH activating system, which provided the desired compounds in high yields (94–96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a–b and 11a–b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.     

Crop rotation sequencing to minimize yield losses of summer-irrigated lowland rice in Myanmar caused by the rice root-knot nematode Meloidogyne graminicola

Abstract

The effect of different rice-based crop rotation sequences on the population densities of Meloidogyne graminicola and on the yield of rice was evaluated in a microplot experiment under lowland rice field conditions. Ten treatments of cropping sequences were grown in four successive growing seasons: continuous growing of the susceptible rice cultivar Thihtatyin (rice-rice-rice-rice), four treatments of 1- season crop rotation sequences (rice-rice-chickpea-rice, rice-rice-black gram-rice, rice-rice-soybean-rice, rice-rice-cowpea-rice), and five treatments of 2-season crop rotation sequences (groundnut-rice-chickpea-rice, green gram-rice-black gram-rice, cowpea-rice-soybean-rice, sesame-rice-cowpea-rice, sunflower-rice-sesame-rice). Population densities of M. graminicola recovered from the rice plants and the nematode multiplication factors (Mf) in the soil in the continuous rice cropping sequence (rice-rice-rice-rice) was the highest among the ten cropping sequences. Lowest nematode Mf in the soil was observed in the 2-season crop rotation sequence sunflower-rice-sesame-rice and the highest was observed in the 1-season crop rotation sequence rice-rice-cowpea-rice among the nine crop rotation sequences. Highest rice yield was obtained in the 2-season crop rotation sequences green gram-rice-black gram-rice, sesame-rice-cowpea-rice and sunflower-rice-sesame-rice, which were about 2 times higher compared with the 1-season crop rotation sequences and about 3 times higher compared with the continuous rice cropping sequence.     

Jaagsiekte sheep retrovirus found in milk macrophages but not in milk lymphocytes or mammary gland epithelia of naturally infected sheep

Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma. JSRV can be transmitted via infected colostrum or milk, which contain somatic cells (SCs) harboring JSRV provirus. Nevertheless, the cell types involved in this form of transmission and the involvement of the mammary gland remain unknown. We separated adherent cells (macrophages and monocytes) by plastic adherence, and lymphocytes (CD4+ and CD8+ T cells, and B cells) by flow cytometry, from SCs in milk samples from 12 naturally infected, PCR blood test JSRV–positive, subclinical ewes. These cell populations were tested by PCR to detect JSRV provirus. The ewes were euthanized, and mammary gland samples were analyzed immunohistochemically to detect JSRV surface protein. We did not detect JSRV provirus in any milk lymphocyte population, but milk adherent cells were positive in 3 of 12 sheep, suggesting a potential major role of this population in the lactogenic transmission of JSRV. Immunohistochemistry did not reveal positive results in mammary epithelial cells, pointing to a lack of participation of the mammary gland in the biological cycle of JSRV and reducing the probability of excretion of free viral particles in colostrum or milk.     

数字林业在天然林保护工程中的应用研究

本文阐述了数字林业的概念及涵义,指出其最初的切入点是国家林业局提出的六大林业生态工程。针对天然林保护工程的现状,提出用数字林业技术解决其存在的问题,构建了基于3S技术的天然林保护工程管理地理信息系统,使天然林保护工程的管理步入规范化、科学化、现代化的轨道。     

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.     

土霉素在黑鲷体内的药物代谢动力学研究

首次报道了黑鲷口服土霉素的药物代谢动力学特征，用高效液相色谱法测定组织中的药物含量，药物在肌肉，血液，肝脏中的平均回归率分别为８５.61%,85.38%,82.005,该方法的检测限可达0.01μg/g，黑鲷１次口服剂量为７５mg/kg的土壤素后，其血液药物浓度－时间数据符合一室开放动力学模型，吸收速率常数（ka)为０.296/h，达峰时间（Ｔamx)为１０.635h,峰浓度（Ｃmax)为１.398μg/ml, 分布半衰期（Ｔ１／２a）为２.339h ,消除半衰期(T1/20β）为46.663h，药时曲线下面积（ＡＵＣ）为１１0.25mg/L.h，黑绸口服药物０.5h后在血液，肥肉，肝脏，肾脏４种组织中就可以检测到药物的存在，药物在１６h的采样点浓度达最高，分别为1.68μg/ml,1.68,2.52,6.77μg/g。     

Fitting growth with the von Bertalanffy growth function: a comparison of three approaches of multivariate analysis of fish growth in aquaculture experiments

Three approaches for multivariate analysis of fish growth in aquaculture experiments with Nile tilapia (Oreochromis niloticus niloticus L.) based on the von Bertalanffy growth curve are presented and compared. The approaches are: an extended Gulland‐and‐Holt (GH) plot, a forced extended GH plot and a multilinear regression analysis for the growth parameter K. All three models provide valuable insight into the major environmental factors influencing the daily growth rate and explain 28–46% of the variance of the observed daily growth rate of the used data set. For all three methods, the modelled parameter is significantly related to the net yield of Nile tilapia and can, therefore, be used for the predictive modelling of management scenarios. The extended GH plot loads the influence of environmental parameters upon L_∞, while the forced extended GH plot and Direct fitting of K load the influence on the growth parameter K. The latter is more in the tradition of aquaculture research. But the forced extended GH plot and Direct fitting of K can only be applied if L_∞ of the cultured species is known, as the selected L_∞ influences the variance in the regression variables.