Can China's vehicular emissions regulation reduce air pollution?-a quasi-natural experiment based on the latest National Vehicular Emissions Standard (stage-VI).

The existing evidence on the environmental effects of vehicular emissions regulation almost comes from developed countries, but the effectiveness of this policy tool in developing countries, especially in China, remains unclear. This study, for the first time, examined the mitigating effects of China's vehicular emissions regulation on air pollution at the prefecture level cities, by using the latest implementation of China's National Vehicular Emissions Standard VI (CHINA-VI) as a quasi-natural experimental process of policy shocks. To this end, monthly data from 2018 to 2020 was applied to construct a difference-in-differences (DID) model. The results showed that pilot cities' air quality index (AQI) significantly decreased by 4.74 compared to non-pilot cities after the implementation of CHINA-VI. Also, the concentration of PM2.5, PM10, and O3 has decreased by 3.6 µg∕m3, 6.4 µg∕m3, and 3.0 µg∕m3, respectively, which means the new China's vehicular emissions regulation has comprehensively improved air quality. The findings are still valid after a series of robustness tests using different estimation methods such as PSM-DID and IV-2SLS. In addition, we also found heterogeneity in the environmental performance of CHINA-VI across cities. Specifically, cities with lower levels of green finance development and public environmental concern showed a greater emissions reduction effect, but smart cities showed a greater emissions reduction effect than non-smart cities.

Transcriptome analysis of developing zebrafish (Danio rerio) embryo following exposure to Gaudichaudione H reveals teratogenicity and cardiovascular defects caused by abnormal iron metabolism.

Gaudichaudione H (GH), a caged polyprenylated xanthone from Garcinia plants, showed anti-cancer and anti-inflammatory effects in vitro. However, the in vivo toxicity of this compound has never been reported. The present study was aimed to address the toxic effects of Gaudichaudione H using zebrafish embryos and larvae as an in vivo test model. The zebrafish embryos were treated with GH having different concentrations (0, 0.28, 0.38 and 0.57 µg/mL). The results revealed that GH induces significant embryonic mortality, decreased heartbeat, cardiotoxicity, cardiovascular defects, increased apoptosis and decreased hemoglobinization in zebrafish embryos and larvae. According to transcriptome analysis, 1841 genes were significantly differentially expressed (1185 down-regulated and 656 up-regulated) after GH treatment. The main functions of these genes were related to iron metabolism pathways. The toxicity of GH on zebrafish embryonic development and cardiovascular may due to large amounts of downregulated genes involved in metabolic pathways and DEGs related to 'Iron ion binding' and 'Heme binding' functions.

Loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome.

BACKGROUND: Periprocedural myocardial infarction is a common complication following percutaneous coronary intervention. The present study was conducted with an aim to compare the safety and efficacy of loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. METHODS: A total of 114 patients with acute coronary syndrome undergoing elective percutaneous coronary intervention were assigned to clopidogrel group (n = 57, the loading and maintenance doses were 300 and 75 mg qd for clopidogrel, and 300 and 100 mg qd for aspirin), or ticagrelor group (n = 57, the loading and maintenance doses were 180 and 90 mg bid for ticagrelor, and 300 and 100 mg qd for aspirin). Cardiac biomarkers were measured before, 8 hours, and 24 hours after percutaneous coronary intervention. The percutaneous coronary intervention-related periprocedural myocardial infarction was defined according to the fourth universal definition of myocardial infarction (2018). RESULTS: The overall incidence of percutaneous coronary intervention-related periprocedural myocardial infarction was 21.1%. The ticagrelor group showed a significantly lower incidence of periprocedural myocardial infarction (12.3% vs 29.8%, p = 0.022) and numerically lower bleeding events (3.5% vs 8.8%, p = 0.242) as compared with clopidogrel group. No patient had major adverse cardiovascular events during the 1-month follow-up. The levels of high-sensitivity C-reactive protein did not differ significantly between the two groups (p > 0.05), indicating that the benefits of ticagrelor were not from its anti-inflammatory effects. Multivariable analysis showed that the use of ticagrelor (odds ratio: 0.50; 95% confidence interval: 0.29-0.87; p = 0.014) and number of stents (odds ratio: 2.75; 95% confidence interval: 1.25-6.06; p = 0.012) were independent predictors of periprocedural myocardial infarction. CONCLUSION: Pretreatment with a loading dose of ticagrelor seems to be superior in reducing the incidence of percutaneous coronary intervention-related periprocedural myocardial infarction in Asian patients with acute coronary syndrome as compared with clopidogrel.

[Research progress on in vitro and in vivo behaviors of poorly soluble Chinese materia medica nanosuspension].

Nanosuspension (also called nanocrystal suspension or nanocrystal) could significantly enhance the saturated solubility and dissolution of insoluble drugs, and improve their bioavailability by reducing particle size and increasing the specific surface, which could then solve the delivery problems of the poorly soluble active ingredients and effective parts of Chinese materia medica (CMM). Based on the brief summaries of nanosuspension preparation methods, this paper would mainly review the in vitro and in vivo behaviors of poorly soluble CMM nanosuspension, discuss and analyze its problems, so as to provide reference and thinking for the further study of nanosuspension drug delivery system of poorly soluble CMM and promote the development and perfection of nanosuspension technology in CMM.

Comparative genomic analysis of Mycobacterium neoaurum MN2 and MN4 substrate and product tolerance.

The microbial bioconversion of sterols can afford valuable steroid precursors, such as 4-androstene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD). The Mycobacterium neoaurum MN4 mutant strain can produce AD in high yield and can tolerate a higher concentration of the substrate phytosterol than the parent strain M. neoaurum MN2. In order to further investigate the mechanisms underlying the enhanced substrate and product tolerance, we performed a genomic analysis of the MN2 and MN4 strains. The genomes were sequenced using a high-throughput approach and analyzed using software for genome assembly, gene prediction and functional annotation, KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation, COG (cluster of orthologous) group cluster analysis, GO cluster analysis, and SNP detection and annotation. Based on comparative genomics, 184 mutations were identified in MN4, the average variant rate of 1 variant every 27,249 bases, with a TS/TV value of 0.5877 and missense mutations in one key sterol degradation genes (ChoM1) and four side chain degradation genes that encode enzymes catalysing ß-oxidation. The results suggest the high AD yield might be due to mutation of ChoM and genes encoding FadE, FadB and FadA ß-oxidation enzymes. This study provides a theoretical basis for further functional genomics analysis and heterologous production of M. neoaurum MN2 secondary metabolites.

Adjunctive loading dose of cilostazol in preventing periprocedural myocardial infarction.

INTRODUCTION: Periprocedural myocardial infarction (PMI) is a common complication of percutaneous coronary intervention (PCI). This study evaluated the safety and efficacy of adjunctive loading dose of cilostazol in preventing PMI in patients with acute coronary syndrome (ACS). METHODS: A total of 113 patients with ACS undergoing PCI were randomized to receive loading doses of dual (aspirin plus clopidogrel; DAPT group; n=57) or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT group; n=56). The loading and maintenance doses were 100 and 50 mg bid for cilostazol. Patients in the TAPT group received adjunctive cilostazol for 1 week. Cardiac biomarkers were measured before PCI, 8 and 24 hours after PCI to determine the incidence of PMI. RESULTS: There was no significant difference in the incidence of PMI between the TAPT and DAPT groups (32.1% vs 47.4%, P=.098). However, in the antiplatelet-naïve subgroup, TAPT significantly lowered the incidence of PMI compared to DAPT (17.9% vs 42.9%, P=.042). In the antiplatelet-treated subgroup, the incidences of PMI were comparable (46.4% vs 51.7%, P=.698). Multivariable logistic analysis showed that antiplatelet-treated (vs antiplatelet-naïve) (hazard ratio [HR]: 2.45; 95% confidence interval [CI]: 1.09-5.52; P=.030) subgroup was independently associated with PMI. However, TAPT (vs DAPT) (HR: 0.51; 95% CI: 0.23-1.14; P=.102) was not an independent protective factor of PMI. CONCLUSIONS: The present single-center, randomized study indicates that TAPT with adjunctive cilostazol was not associated with lower incidence of PCI-related PMI in patients with ACS. Further study with large study population is needed to get definite conclusions.

Low-dose adjunctive cilostazol in patients with complex lesions undergoing percutaneous coronary intervention.

Patients with complex coronary lesions undergoing percutaneous coronary intervention (PCI) have more major adverse cardiac events (MACE) than do those with simpler cases. Therefore, intensive antiplatelet therapy might be needed in these patients. A total of 127 patients with complex lesions undergoing PCI in the Second Hospital of Tianjin Medical University from October 2012 to April 2014 were randomized to receive either dual (aspirin plus clopidogrel, DAPT, n = 66), or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT, n = 61). Patients in the TAPT group received low-dose cilostazol (100 mg loading, followed with 50 mg twice per day) for 3-6 months. The primary endpoint was composite MACE. The complex coronary target lesions were defined as at least one of the following: left main disease; severe 3-vessel disease; chronic total occlusion lesions; true bifurcation lesion; ostial lesions; severe calcified lesions; and highly thrombotic lesions. The two groups had similar baseline clinical and angiographic characteristics. One-year clinical outcomes showed that the TAPT group had significantly lower incidences of myocardial infarction (1.6% vs 13.6%, P = 0.018) and MACE (1.6% vs 16.7%, P = 0.004) than DAPT group. The DAPT group had two cases of stent thrombosis, while the TAPT group did not. Furthermore, adjunctive low-dose cilostazol didn't significantly increase the incidence of bleeding events (26.2% vs 19.7%, P = 0.381) regardless of major (4.9% vs 4.5%, P = 0.921) or minor (21.3% vs 15.2%, P = 0.368) bleeding events. In conclusion, low-dose adjunctive cilostazol seems superior to dual antiplatelet therapy in reducing recurrent ischemic events in patients with complex coronary lesions and the two test groups have a similar incidence of bleeding events.