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Research on the stereochemistry of natural products, especially that of flexible macrocyclic molecules, has always been a huge challenge. Cembranes diterpenoids are a typical class of flexible macrocyclic molecules, whose configurations are often determined by coupling constant and nuclear Overhauser effect (NOE), both of which are nuclear magnetic resonance (NMR) parameters with local character. The development of methods such as residual dipolar coupling (RDC) and quantum chemical calculations has further expanded the toolbox for solving stereochemical problems. RDC, as an NMR parameter with non-local character, has not only been reported in the structure construction and function research of biomolecules such as proteins and nucleic acids, but has also gradually been applied to the configuration determination of natural products, contributing significantly to the stereochemical research on drug molecules. At present, there are few reports of RDC application in determining the configurations of cembranes diterpenoids. Here, the stereochemical configuration of sinulariol Z is investigated by RDC for the first time and confirmed by X-ray diffraction, further demonstrating the feasibility of RDC in the stereochemical study on cembranes diterpenoids.

Objective To calculate the leakage rate of the automated watering system in Tsinghua University Laboratory Animal Resources Center, to evaluate the safety of the system, and provide references for selection, maintenance, and management of automated watering systems in animal facilities. Methods This study investigated the automated watering system installed in South and North Barriers of Tsinghua University Laboratory Animal Resources Center (Phase II). Water leakage monitoring was conducted over two periods, one over a period of 3 years and the other over 1.5 years. The occurrence of water leakage events at the two barriers during the monitoring period was statistically analyzed, classifying the causes into four categories: mishandling by personnel, animal behavior, obstruction by foreign objects, and deformation of fittings. The total daily leakage rate due to these causes and the daily leakage rate caused by quality issues, i.e. obstruction by foreign objects and deformation of fittings were calculated. Further analysis and discussion focused on the causes of water leakage and its impact on the facilities. At the same time, the number of caretakers at the end of the monitoring period in the Phase I facility without automated watering system and the Phase II facility with automated watering system were counted. Finally the difference in the number of cages per capita under the two watering systems was calculated. ResultsA total of 52 water leakage incidents occurred in both areas during the monitoring period, with a total daily leakage rate of 0.000 13%. Among them, 31 were caused by personnel mishandling, accounting for approximately 60% of total leakages. Enhanced training, supervision, inspection, and effective reminder measures could reduce leakage caused by personnel mishandling. There were 2 cases of water leakages caused by animal behavior, 0 leakage due to obstruction by foreign objects, and 19 leakages due to system quality issues, with a daily leakage rate of 0.000 07%. According to the operation data of Tsinghua University Laboratory Animal Resources Center, the average number of cages managed per person in facilities equipped with the automated watering system was 908, compared to 570 cages in facilities without the automated watering system. This represents an approximate 59% increase in the number of cages managed per person with the adoption of the automated watering system. Conclusion The daily leakage rate of the automated watering system in the Tsinghua University Laboratory Animal Resources Center is significantly lower than the theoretical design rate of 0.003%, which demonstrates the system's safety and effectiveness. Additionally, the adoption of an automated watering system can significantly enhance caretaking efficiency. While initial investments in the system are required, the subsequent increase in efficiency leads to a continuous decrease in labor costs, thereby reducing the total operational expenses of the facility. In the context of modernizing animal facility construction, automated watering systems are becoming an essential consideration in facility design and operation.

Objective To investigate the effect and its mechanism of Guanxinning tablet on carotid atherosclerotic plaque in a rat model. Methods The rats were randomly divided into control group, model group (to construct carotid atherosclerosis plaque model), Guanxinning groups with low, medium and high dose of Guanxinning tablet (150,300 and 600 mg/kg), atorvastatin group (2 mg/kg), lithiumchloridemonohydrate(LiCl) (Wnt/β-catenin pathway activator) group (15 mg/kg), and Guanxinning plus LiCl group (600 mg/kg Guanxinning tablets+15 mg/kg LiCl), with 12 rats in each group. The intervention began at the third week and was administered once a day for 8 weeks. Olympus Au2700 automatic biochemical analyzer was used to detect the level of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) in rat serum; ELISA was applied to detect the level of monocyte chemotactic protein (MCP-1) and hyper-sensitive C-reactive protein (hs-CRP) in rat serum; the level of oxidized low density lipoprotein (ox-LDL) and malondialdehyde (MDA) in rat serum were detected by spectrophotometry; HE staining was applied to find pathological changes in the common carotid artery of rats; Western blot was applied to detect the expression of Wnt3a, matrix metalloproteinase-9 (MMP-9) and β-catenin in rat common carotid artery. Results Compared with the control group, the level of TG, TC, LDL, MCP-1, hs-CRP, ox-LDL, protein expression of MDA, MMP-9, Wnt3a, β-catenin and total plaque area/total arterial area ratio increased, the HDL level decreased in model group (P＜0.05); compared with the model group, the level of TG, TC, LDL, MCP-1, hs-CRP, ox-LDL, MDA, expression of MMP-9, Wnt3a, β-catenin protein and total plaque area/total arterial area ratio in the low, medium, and high dose groups of Guanxinning tablets decreased, the HDL level increased. The effect of Guanxinning tablets was dose-dependent, and the change trend of corresponding indicators in the LiCl group was opposite to the above (P＜0.05); compared with the high dose group of Guanxinning tablets, the TG, TC, LDL, MCP-1, hs-CRP, ox-LDL, MDA levels, MMP-9, Wnt3a, β-catenin protein expression, and total plaque area/total arterial area ratio in the high dose+LiCl group of Guanxinning tablets increased, the HDL level decreased(P＜0.05). Conclusions Guanxinning tablet can inhibit the formation of atherosclerotic plaque in rats and the mechanismis potentially related to the regulation of Wnt/β-catenin pathway.

Prior to the last decade, the logistics industry trended towards the development of mega-warehouse facilities in suburban settings far from core markets, creating a phenomenon known as logistics sprawl. This trend is particularly prominent in Southern California (Figure 1). Since the 2008-2009 economic crisis, however, the trend has shifted. The rise of e-commerce may have influenced supply chain decisions to locate warehouses and distribution centers closer to denser urban areas to enable faster deliveries to consumers. The changes in size and spatial distribution of warehouses and distribution centers as well as the environmental and equity implications of these changes are not fully understood. As warehouses and distribution centers locate in denser urban areas, they may introduce additional diesel truck traffic into disadvantaged and low-income communities.To gain a better understanding of how the spatial distribution and size of freight facilities are changing and the implications of these changes for disadvantaged and low-income communities, researchers at the University of California, Davis analyzed aggregate data about the number of warehouses and distribution centers and disaggregate real estate data of purchases and leases during the last three decades in California. They also analyzed the relationship between freight facilities and communities of concern using the California Environmental Protection Agency’s CalEnviroScreen 3.0 tool. The research focused on the San Diego, Los Angeles, San Francisco, San Joaquin Valley, and Sacramento regions. Key findings from the research are presented in this brief.

This work addresses the distribution of warehouses and distribution centers (W&DCs) influenced by e-commerce, through spatial analysis and econometric modelling. Specifically, this work analyzes the concentration of W&DCs in various metropolitan planning organizations (MPOs) in California between 1989 and 2016-18; and studies the spatial relationships between W&DC distribution and other demographic and environmental factors through econometric modeling techniques. The work conducts analyses to uncover common trends in W&DC distribution. The analyses used aggregate establishment, employment, and other socio-economic information, complemented with transportation related variables. The results: 1) confirm that the weighted geometric centers of W&DCs have shifted slightly towards city central areas in all five MPOs; 2) W&DCs show a non-decreasing trend between 2008 and 2016; and 3) areas with more serious environmental problems are more likely to have W&DCs. A disaggregate analyses of properties sold and leased in one of the study regions shows a trend where businesses are buying or leasing smaller facilities, closer to the core of consumer demand. Among other factors, the growth of e-commerce sales, and expedited delivery services, which require proximity to the customers, may explain these trends. The study results provide insights for planners and policy decision makers, and will be of interest to practitioners, public and private entities, and academia. Caltrans, MPOs, and affiliated institutions of the National Center for Sustainable Transportation will directly benefit from the results as they want to avoid equity issues brought by the fast development of e-commerce, and its potential impact on W&DC distribution.