Enantioselective Transformations in the Synthesis of Therapeutic Agents.

The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, the efficient synthesis of enantiopure pharmaceuticals or their synthetic intermediates poses a profound challenge to medicinal and process chemists. The significant advancement in asymmetric catalysis has provided an effective and reliable solution to this challenge. The successful application of transition metal catalysis, organocatalysis, and biocatalysis to the medicinal and pharmaceutical industries has promoted drug discovery by efficient and precise preparation of enantio-enriched therapeutic agents, and facilitated the industrial production of active pharmaceutical ingredient in an economic and environmentally friendly fashion. The present review summarizes the most recent applications (2008-2022) of asymmetric catalysis in the pharmaceutical industry ranging from process scales to pilot and industrial levels. It also showcases the latest achievements and trends in the asymmetric synthesis of therapeutic agents with state of the art technologies of asymmetric catalysis.

[Life Cycle Environmental Impact Assessment on Different Modes of Greenhouse Vegetable Production in the North China Plain].

Organic agriculture has a higher potential than traditional agriculture to reduce environmental emissions. However, heavy metals in organic manure inevitably exacerbate eco-toxicity. At present, there are few studies on systematically and comprehensively evaluating the effects of different production modes on the environmental impact of vegetable production in the North China Plain (NCP). The objective of this study is to provide a theoretical direction for reducing the negative impact of greenhouse vegetable production. In this study, we used a greenhouse eggplant production (2013-2016) as case study and conducted a field experiment in Quzhou County, Hebei Province, China. The life cycle assessment (LCA) approach was used to analyze and compare the production and environmental impacts of eggplant production under three modes:conventional, integrated, and organic. The results showed that the potential for water contamination, eutrophication, and soil contamination was high among the three modes, ranging from 82.05% to 84.02%, 10.29% to 12.32%, and 2.62% to 3.48%, respectively. This is occurred mainly in the arable farming subsystem and is attributed to the loss of nitrogen (N) and phosphorus (P), pesticide residues, and heavy metals in organic manure. The environmental impact index of the integrated mode is the lowest, with a value of 0.596, which is 30.3% and 6.7% lower than those of the conventional and organic modes. The integrated mode significantly reduces the emission of pollutants from the greenhouse vegetable production in the arable farming subsystem; therefore, it is the best management practice. In the integrated mode, the environmental costs of producing one ton of eggplant are 46.6 J for energy depletion, 81.9 m2 for land occupation, 0.0046 m3 for water depletion, 0.0054 kg (CO2-eq) for global warming, 0.0060 kg (SO2-eq) for acidification, 0.0735 kg (PO4-eq) for aquatic eutrophication, 2.84E-05 kg (1,4-DCB-eq) for human toxicity, 0.4892 kg (1,4-DCB-eq) for aquatic eco-toxicity, and 0.0174 kg (1,4-DCB-eq) for soil eco-toxicity. Optimizing field management measures such as the application of biological pesticides, using high quality organic fertilizer, and improving the efficiency of N and P use, can better control the negative environmental impacts in the life cycle of vegetable production and improve environmental sustainability in the NCP.

Optimization of an on-board imaging system for extremely rapid radiation therapy.

PURPOSE: Next-generation extremely rapid radiation therapy systems could mitigate the need for motion management, improve patient comfort during the treatment, and increase patient throughput for cost effectiveness. Such systems require an on-board imaging system that is competitively priced, fast, and of sufficiently high quality to allow good registration between the image taken on the day of treatment and the image taken the day of treatment planning. In this study, three different detectors for a custom on-board CT system were investigated to select the best design for integration with an extremely rapid radiation therapy system. METHODS: Three different CT detectors are proposed: low-resolution (all 4×4 mm pixels), medium-resolution (a combination of 4×4 mm pixels and 2×2 mm pixels), and high-resolution (all 1×1 mm pixels). An in-house program was used to generate projection images of a numerical anthropomorphic phantom and to reconstruct the projections into CT datasets, henceforth called "realistic" images. Scatter was calculated using a separate Monte Carlo simulation, and the model included an antiscatter grid and bowtie filter. Diagnostic-quality images of the phantom were generated to represent the patient scan at the time of treatment planning. Commercial deformable registration software was used to register the diagnostic-quality scan to images produced by the various on-board detector configurations. The deformation fields were compared against a "gold standard" deformation field generated by registering initial and deformed images of the numerical phantoms that were used to make the diagnostic and treatment-day images. Registrations of on-board imaging system data were judged by the amount their deformation fields differed from the corresponding gold standard deformation fields--the smaller the difference, the better the system. To evaluate the registrations, the pointwise distance between gold standard and realistic registration deformation fields was computed. RESULTS: By most global metrics (e.g., mean, median, and maximum pointwise distance), the high-resolution detector had the best performance but the medium-resolution detector was comparable. For all medium- and high-resolution detector registrations, mean error between the realistic and gold standard deformation fields was less than 4 mm. By pointwise metrics (e.g., tracking a small lesion), the high- and medium-resolution detectors performed similarly. For these detectors, the smallest error between the realistic and gold standard registrations was 0.6 mm and the largest error was 3.6 mm. CONCLUSIONS: The medium-resolution CT detector was selected as the best for an extremely rapid radiation therapy system. In essentially all test cases, data from this detector produced a significantly better registration than data from the low-resolution detector and a comparable registration to data from the high-resolution detector. The medium-resolution detector provides an appropriate compromise between registration accuracy and system cost.

[Estimation on disease burden related to hepatitis B virus infection in Shandong province of China].

OBJECTIVE: To comprehensively measure the burden of hepatitis B, liver cirrhosis and liver cancer in Shandong province, using disability-adjusted life years (DALYs) to estimate the disease burden attribute to hepatitis B virus (HBV) infection. METHODS: Based on the mortality data of hepatitis B, liver cirrhosis and liver cancer derived from the third National Sampling Retrospective Survey for Causes of Death during 2004 and 2005, the incidence data of hepatitis B and the prevalence and the disability weights of liver cancer gained from the Shandong Cancer Prevalence Sampling Survey in 2007, we calculated the years of life lost (YLLs), years lived with disability (YLDs) and DALYs of three diseases following the procedures developed for the global burden of disease (GBD) study to ensure the comparability. RESULTS: The total burden for hepatitis B, liver cirrhosis and liver cancer were 211,616 (39,377 YLLs and 172,239 YLDs), 16,783 (13,497 YLLs and 3286 YLDs) and 247,795 (240,236 YLLs and 7559 YLDs) DALYs in 2005 respectively, and men were 2.19, 2.36 and 3.16 times as that for women, respectively in Shandong province. The burden for hepatitis B was mainly because of disability (81.39%). However, most burden on liver cirrhosis and liver cancer were due to premature death (80.42% and 96.95%). The burden of each patient related to hepatitis B, liver cirrhosis and liver cancer were 4.8, 13.73 and 11.11 respectively. CONCLUSION: Hepatitis B, liver cirrhosis and liver cancer caused considerable burden to the people living in Shandong province, indicating that the control of hepatitis B virus infection would bring huge potential benefits.