[Scenario Simulation and Effects Assessment of Co-control on Pollution and Carbon Emission Reduction in Beijing].

Focused on the key areas of energy, buildings, industry, and transportation, with 2020 as the base year and 2035 as the target year, we respectively designed the baseline scenario, policy scenario, and enhanced scenario, calculated the emission reduction potential of air pollutants and CO2 of Beijing, and constructed an assessment method of co-control effect gradation index to evaluate the co-control effect of air pollutants and CO2 in the policy scenario and enhanced scenario. The results showed that in the policy scenario and enhanced scenario, the reduction rates of air pollutants emissions will reach 11%-75% and 12%-94%, respectively, and reduction rates of CO2 emissions will reach 41% and 52%, respectively, compared with those from the baseline scenario. Optimizing vehicle structure had the largest contribution to the emission reduction of NOx, VOCs, and CO2, and the emission reduction rates will reach 74%, 80%, and 31% in the policy scenario and 68%, 74%, and 22% in the enhanced scenario, respectively. Replacing coal-fired with clean energy in rural areas had the largest contribution to the emission reduction of SO2; the emission reduction rates will reach 47% and 35% in the policy scenario and enhanced scenario, respectively. Improving the green level of new buildings had the largest contribution to the emission reduction of PM10; the emission reduction rates will reach 79% and 74% in the policy scenario and enhanced scenario, respectively. Optimizing travel structure and promoting green development of digital infrastructure had the best co-control effect. The co-control effect of replacing coal-fired with clean energy in rural areas, optimizing vehicle structure, and promoting green upgrading of the manufacturing industry will be improved to a better status in the enhanced scenario. More attention should be paid to improving the proportion of green trips, implementing the promotion of new energy vehicles, and the green transportation of goods to reduce emissions in the field of transportation. At the same time, with the continuous improvement in electrification level in the end energy consumption structure, the proportion of green electricity should be increased by expanding local renewable energy power production and increasing external green electricity transmission capacity, to enhance the co-control effect of pollution and carbon reduction.

Synthesis and Evaluation of Novel 2H-Benzo[e]-[1,2,4]thiadiazine 1,1-Dioxide Derivatives as PI3Kδ Inhibitors.

In previous work, we applied the rotation-limiting strategy and introduced a substituent at the 3-position of the pyrazolo [3,4-d]pyrimidin-4-amine as the affinity element to interact with the deeper hydrophobic pocket, discovered a series of novel quinazolinones as potent PI3Kδ inhibitors. Among them, the indole derivative 3 is one of the most selective PI3Kδ inhibitors and the 3,4-dimethoxyphenyl derivative 4 is a potent and selective dual PI3Kδ/γ inhibitor. In this study, we replaced the carbonyl group in the quinazolinone core with a sulfonyl group, designed a series of novel 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives as PI3Kδ inhibitors. After the reduction of nitro group in N-(2,6-dimethylphenyl)-2-nitrobenzenesulfonamide 5 and N-(2,6-dimethylphenyl)-2-nitro-5-fluorobenzenesulfonamide 6, the resulting 2-aminobenzenesulfonamides were reacted with trimethyl orthoacetate to give the 3-methyl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives. After bromination of the 3-methyl group, the nucleophilic substitution with the 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine provided the respective iodide derivatives, which were further reacted with a series of arylboronic acids via Suzuki coupling to furnish the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives 15a-J and 16a-d. In agreement with the quinazolinone derivatives, the introduction of a 5-indolyl or 3,4-dimethoxyphenyl at the affinity pocket generated the most potent analogues 15a and 15b with the IC50 values of 217 to 266 nM, respectively. In comparison with the quinazolinone lead compounds 3 and 4, these 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives exhibited much decreased PI3Kδ inhibitory potency, but maintained the high selectivity over other PI3K isoforms. Unlike the quinazolinone lead compound 4 that was a dual PI3Kδ/γ inhibitor, the benzthiadiazine 1,1-dioxide 15b with the same 3,4-dimethoxyphenyl moiety was more than 21-fold selective over PI3Kγ. Moreover, the introducing of a fluorine atom at the 7-position of the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide core, in general, was not favored for the PI3Kδ inhibitory activity. In agreement with their high PI3Kδ selectivity, 15a and 15b significantly inhibited the SU-DHL-6 cell proliferation.

[Effects of Tongbi capsule on joint lesions in rabbits with rheumatoid arthritis].

The purpose of this experiment is to observe the effects of Tongbi capsule on joint lesions in rabbit with rheumatoid arthritis induced by ovalbumin and explore the mechanism in order to provide reference for clinical application of Tongbi capsule. Rheumatoid arthritis in rabbits was induced by subcutaneous injection of emulsions of ovalbumin and Freund's complete adjuvant and intra articular injection of ovalbumin. After successful modeling, 30 New Zealand rabbits with arthritis were randomly divided into model control group, the high, medium and low dose groups of Tongbi capsule (90, 45, 22.5 mg·kg⁻¹) and prednisone group (5 mg·kg⁻¹). Another six normal rabbits were used as normal control group. After 24 hours of modeling, the rabbits in Tongbi capsule groups received intragastric (i.g.) administrations of Tongbi capsule at 90, 45, 22.5 mg·kg⁻¹·d⁻¹, and the rabbits of prednisone group received i.g. administrations of prednisone at 5 mg·kg⁻¹·d⁻¹ for 2 weeks. The rabbits in normal and model groups received the same volume of distilled water at the same time. The swelling degree of rabbit knee joint and local skin temperature were observed daily. After two weeks of administration, pathological changes of rabbit knee joint were examined by magnetic resonance imaging (MRI); the morphological changes of articular cartilage and synovial membrane were observed by microscope; and the contents of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme linked immunosorbent assay (ELISA).The results showed that 24 h after modeling, the knee joints of the rabbits were swollen, with red or dark redlocal skin, and fever, elevated local skin temperature and increased diameters of knee joints. Two weeks after modeling, the swelling of rabbit knee joints was obvious in model group; the joint cavities were filled with purulent fluid; joint synovial membranes were obviously thickened, and even joint cavities were fibrotic and cartilage surfaces showed slight defect; the surface of articular cartilage was obvious fibrosis; synovial epithelial cell proliferation was obvious and accompanied by extensive inflammatory cell infiltration; the levels of IL-1 and TNF-α were significantly higher as compared with those seen in model rabbits (P<0.05, P<0.01). After 1 and 2 weeks of administration, knee joint diameters and local skin temperatures were smaller or lower than thosein model group (P<0.05, P<0.01); The lesions of joint cartilage and synovial of all rabbits in each group were less than those in model group; IL-1 and TNF-α levels in serum were also lower than those in model group (P<0.05, P<0.01). The results reveal that high and medium doses of Tongbi capsule can suppress rheumatoid arthritis induced by ovalbumin in rabbits, reduce joint swelling, inhibit synovial epithelial and fiber hyperplasia and inflammatory cell infiltration, and alleviate articular cartilage damage. The mechanism may be associated with decreasing IL-1 and TNF-α levels in serum.

Evaluation of the effect of glutathione on cisplatin antitumor activity and kidney injury at different administration times.

Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most potent anticancer drugs. However, the therapeutic value of CDDP is greatly compromised by its dose-limiting nephrotoxicity. This study was performed to investigate whether reduced glutathione (GSH) was able to reduce the kidney injury induced by CDDP and whether it affected the anticancer activity of CDDP in vivo and in vitro. In in vivo experiments, mice were divided into five groups: control, CDDP only and three GSH treatment groups. Blood samples were collected 72 h after CDDP administration to determine the levels of blood urea nitrogen (BUN) and plasma creatinine (Cr). In addition, we examined antioxidative parameters, malondialdehyde (MDA) levels and histopathological changes in the kidney. In order to investigate whether GSH affected the anticancer activity of CDDP, we performed a sulforhodamine B (SRB) assay to determine the anti-proliferative effect in three tumor cell lines of treatment with CDDP alone or combined with GSH and examined the cell morphology. The results revealed that GSH decreased the BUN and Cr levels in plasma, ameliorated the pathological changes induced by CDDP and enhanced the endogenous antioxidant capacities in all three GSH groups. Furthermore, GSH significantly inhibited the growth of the three tumor cell lines when combined with CDDP and did not affect the inhibitory effect of CDDP on the carcinoma cell proliferation. In addition, we found no differences among the three GSH groups. These findings suggest that GSH is able to attenuate the nephrotoxicity induced by CDDP, not only when administered prior to CDDP, but also when administered at the same time as or subsequent to CDDP administration, without affecting the anticancer activity of CDDP. Thus, the administration of GSH is a promising approach for attenuating the nephrotoxicity caused by CDDP.

[Effect of electroacupuncture on proliferation of astrocytes after spinal cord injury].

OBJECTIVE: To explore the mechanism of acupuncture in treatment of spinal cord injury (SCI). METHODS: Adult Wistar rats were used to make SCI model by Allen's method. The SCI rats were treated with electroacupuncture (EA) at acupoints of the Governor Vessel for 3 days, 1 week, 2 weeks or 4 weeks. Normal group and spinal cord injury group were used as controls. The number and morphology of astrocytes in each group were investigated by electron microscope, immunohistochemistry and in situs hybridization methods. The expression of glial fibroblast acid protein (GFAP) mRNA in the injured spinal cord was detected by reverse transcription polymerase (RP-PCR). RESULTS: The mitochondria and ribosomes of astrocytes in the EA group increased. The number of astrocytes increased after SCI, in gray matter being more than that in the white matter, in the caudal being more than that in the rostral. The expression of GFAP mRNA in the EA group was significantly lower than that in the control group. CONCLUSION: Electroacupuncture can inhibit the reactive proliferation of the astrocytes after spinal cord injury and prevent formation of the glial scar.