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The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34+ cells and CD34+CD38− cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications. Image 1 • A total of 37 of pyrimidoindole derivatives were synthesized and 6 of those analogs were identified to be effective in proliferating HSCs. • Analog 11 is the most potent compound in promoting HSC ex vivo expansion. • The potency of 11 is comparable or superior to those of reported small molecule HSC ex vivo expansion agents. • HSCs expanded by analog 11 retained colony-forming unit property and adequate multi-lineage differentiation capacity. [ABSTRACT FROM AUTHOR]

Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b , 3e , 4b , and 4e demonstrated K i values of 5–6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities. [ABSTRACT FROM AUTHOR]

Based on the Lagrangian random walk particle tracking method and the global ocean reanalysis data, this study simulated the drift-diffusion process in ocean of microplastic particles (density less than seawater) discharged by coastal cities in China for 12 consecutive years. The results reveal that most of the microplastics (80.33%) essentially end up ashore or in the marginal seas around China, a small portion of microplastics (18.22%) enter the Sea of Japan and the Northwest Pacific Ocean via the Tsushima Strait and the Osumi-Kaikyo with the Kuroshio Tide, a very small portion of microplastics (1.45%) enter into the waters of Southeast Asian countries along with the west boundary current of South China Sea. The concentration distribution characteristics have obvious seasonal variation in the high concentration areas (the marginal seas around China and Sea of Japan). The mainly destination area of microplastics released in different cities is different. • Microplastic's transportation in ocean discharged by China's coastal cities. • Most of the microplastics (80.33%) end up ashore or in the marginal seas around China. • Two channels (18.22%, 1.45%) are exported from the marginal seas around China. • The concentration have seasonal variation in the marginal seas around China and Japan. • The microplastics's mainly destination area released in different cities is different. [ABSTRACT FROM AUTHOR]

On 06 January 2018, the Sanchi tanker collided with a Hong Kong-flagged cargo ship at 30°42′42″N, 124°56′42″E in the East China Sea (ECS). In this paper, we used a Northwest Pacific (NWP) operational oil spill forecasting system of National Marine Environmental Forecasting Center of China (NMEFC) to forecast the oil drifting trajectory during Sanchi collision accident. In order to reveal the major errors sources and improve the accuracy of the forecasting system, we designed five numeric simulation scenarios. In the five scenarios, we input the different current and wind forcing data into the forecasting system, and set the different oil released time. By the analysis and discussion of the five numeric simulation results, we drew the conclusions following: 1) The error of wind and the inaccuracy released time of oil were the major error sources of the NWP operational oil spill forecasting system of NMEFC during the accident. 2) We should further strengthen the observation of the complicated vortex region of Kuroshio Current to improve the prediction accuracy of material transport in ocean. 3) In the event that this information is unavailable, uncertainty analysis should be conducted by simulating the oil spill on all kinds of different released conditions. • We designed five numeric simulation scenarios to reveal the major errors sources. • Wind error and inaccuracy released time of oil were the major error sources. • We should further strengthen the observation of Kuroshio Current. • Uncertainty analysis should be conducted if released time of oil is inaccuracy. [ABSTRACT FROM AUTHOR]