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[Image: see text] We report herein the discovery of quinazolindiones as potent and selective tankyrase inhibitors. Elucidation of the structure–activity relationship of the lead compound 1g led to truncated analogues that have good potency in cells, pharmacokinetic (PK) properties, and excellent selectivity. Compound 21 exhibited excellent potencies in cells and proliferation studies, good selectivity, in vitro activities, and an excellent PK profile. Compound 21 also inhibited H292 xenograft tumor growth in nude mice. The synthesis, biological, pharmacokinetic, in vivo efficacy studies, and safety profiles of compounds are presented.

Building on near-real-time and spatially explicit estimates of daily carbon dioxide (CO2) emissions, here we present and analyze a new city-level dataset of fossil fuel and cement emissions. Carbon Monitor Cities provides daily, city-level estimates of emissions from January 2019 through December 2021 for 1500 cities in 46 countries, and disaggregates five sectors: power generation, residential (buildings), industry, ground transportation, and aviation. The goal of this dataset is to improve the timeliness and temporal resolution of city-level emission inventories and includes estimates for both functional urban areas and city administrative areas that are consistent with global and regional totals. Comparisons with other datasets (i.e. CEADs, MEIC, Vulcan, and CDP) were performed, and we estimate the overall uncertainty to be 21.7%. Carbon Monitor Cities is a near-real-time, city-level emission dataset that includes cities around the world, including the first estimates for many cities in low-income countries. A more complete description of this dataset is published in Scientific Data (https://doi.org/10.1038/s41597-022-01657-z).

Materials processed using micro-manufacturing technologies exhibit significantly different properties compared to those produced using conventional macro-manufacturing techniques. In this paper, the uniaxial tensile tests were performed on the thin sheet specimens of pure copper to investigate how the sheet thickness impacts the flow stress. The experimental results show a continuous decrease of flow stress as the sheet thickness reduces from 200 to 100 μm, but an increase of flow stress with further reduction in thickness. Firstly, by introducing the ratio of surface grains, the decrease trend of flow stress was explained on the basis of surface layer model. Secondly, the strengthening effect of Cu2O film was clearly demonstrated by the x-ray diffraction and electrodeposition process. Finally, considering the effects of Cu2O film and free surface layer, the mechanical properties of Cu2O film was studied, which is helpful to explain the material behavior in micro sheet forming.

In micro-manufacture field, the micro-geometry is usually produced by the coining process, and therefore the researches on the coining process of micro-geometry are necessary. After designing and machining die with different diameters of micro-holes, the size effects on micro-cylinder deformation in the coining process are experimentally studied in this paper. The ratio of the micro-cylinder height h to micro-hole diameter D is selected as the evaluation criteria for the forming degree of micro-cylinder, and the effect of micro-cylinder size on the ratio h/D is studied. Using microscope, electron backscatter diffraction, and Vickers hardness test, the influences of grain distribution and orientation are also investigated. The research results could guide the manufacturing of the parts with micro-geometry.

In the past five years, the situation of blood supply shortage in China mainland was increasingly grim. The occurrence of blood supply shortage has inevitable objective reasons, but more are subjective reasons that can be avoided originally. The purpose of this paper is that through the analysis of the subjective reasons for the formation of blood supply shortage, to seek the effective way to solve the problem. Analysis shows that the main four causes of blood supply shortage are imperfect incentive mechanism, crisis of confidence, in short supply and the weak foundation. The governance path of blood supply shortages should be multi-governance dominated by the government and involved with multi-organization participation. The government should play a leading role; Blood collection and supply department should improve its service level; Medical institutions should improve the level of scientific and reasonable blood use; Nongovernmental organizations (NGOs) should play their own advantages, to participate in the propaganda and the donation work; The news media should actively participate in social public welfare publicity of blood donation; The general public should trust and support for acquisition and use of blood. For the immediate interests of the public, the relevant departments and personnel should work together and perform its own functions, only in this way the blood supply shortage problem can be effectively alleviated or thoroughly solved.

Wnt signaling pathway plays important roles in the biology of stem cells in maintaining their selfrenewal property. Glycogen synthase kinase-3 (GSK-3) inhibitors, the Wnt signaling agonists, maintain the pluripotency of embryonic stem cells. We report here that a synthetic GSK-3 inhibitor, 6- bromoindirubin-30-oxime (BIO), showed opposite effects on the expansion of human primitive hematopoietic cells isolated from umbilical cord blood (UCB). In combination with human c-kit ligand (KL), BIO at low concentration (0.2 mM) enhanced the expansion of UCB CD34+ cells, which was BIO structure and exposure time dependent; however, at high concentration (2 mM) it inhibited the expansion of the cells. Furthermore, hematopoietic stem cells (HSCs) were exhausted when the UCB CD34+ cells were exposed to 0.2 mM BIO and KL longer than 2 days. In conclusion, the use of BIO in expansion of UCB HSCs remains a significant challenge. Refereed/Peer-reviewed