Effects of Early Pollution Control Measures on Secondary Species of PM2.5 in Jiaozuo, China.

Various measures for reducing air pollution have been promulgated since 2013 in China. To investigate the synergistic results of emission control and meteorological environment, PM2.5 samples collected from October 2013 to July 2016 and November 2018 to October 2019 in Jiaozuo city were analyzed for their compositions, secondary species (Ss) variations, and factors changing for Ss formation. The results showed that the concentrations of sulfate, nitrate, ammonium, and secondary organic aerosols (SOAs) generally decreased over the same seasonal period during these years. In addition, the concentrations and proportions of each Ss increased with the increase in the PM2.5 level in these years, implying that although PM2.5 levels have been reduced by various control policies, Ss formation would remain the major contributor to PM elevations. The enhanced effects of gas-phase reactions on intensification of sulfate, SOA, and PM were observed in 2018-2019, which was consistent with the elevation of nitrate and SOA at PM levels of >150 µg/m3. Only sulfate in all PM levels sharply decreased after 2015, showing the fine effect of coal-related pollution control and the importance of collaborative control of NO x , volatile organic compounds, and organic aerosol emissions with SO2 emissions in the future.

Understanding the emission pattern and source contribution of hazardous air pollutants from open burning of municipal solid waste in China.

The open burning of municipal solid waste (MSW) is common in China. Therein, low-temperature anoxic combustion results in the emission of hazardous air pollutants. This study employed a dilution sampling system to conduct open burning testing on MSW samples from different functional urban areas. Additionally, modified combustion efficiency was used to distinguish smoldering and flaming combustion in two of the most common open burning practices in China: pile-up burning and barrel burning. The sampled pollutants included gaseous pollutants (e.g., CO2, CO, SO2, and NOx) and fine particles (PM2.5). This study also analyzed the carbonization compounds, 9 water-soluble ions, and 8 toxic heavy metals in PM2.5. Emission factors of air pollutants from open burning of different MSW compositions and burning modes were determined. The composition of PM2.5 from MSW open burning comprised average 43.9%, 22.5%, and 0.4% of organic carbon (OC), water-soluble ions, and toxic heavy metals (THMs), respectively. OC was found to be the primary component of PM2.5. Based on localized emission factor database, the emissions and source contribution of open burning of MSW in China were quantified. The open burning of MSW can contribute averaged 8.7%, 16.7%, 3.8%, 1.3% of PM2.5, OC, THMs, and gaseous air pollutants of reported emissions of anthropogenic sources, respectively. This work can complement current anthropogenic emission inventory and assist policy-making.

[Characteristics of Heavy Metal Pollutants of PM2.5 from Open Burning of Municipal Solid Waste (MSW) and the Associated Exposure Health Risks].

The characteristics and health risk assessment for heavy metal pollutants in PM2.5 discharged from the open burning of municipal solid waste (MSW) in different functional areas were studied using a flue gas diluted sampling system. The two common open burning modes of barrel and natural pile-up burning were considered. The results show that the concentration of zinc (Zn) was the highest among the heavy metals produced by five different components of waste incineration, ranging from 1324.03 to 3703.12 mg·kg-1. The concentration of cadmium (Cd) was the lowest, ranging from 20.25 to 63.68 mg·kg-1. According to the geo-accumulation index, lead (Pb), Zn, arsenic (As), and Cd were highly polluted in the measured MSW samples, and all four of these metals reached moderate or higher levels of pollution under natural pile-up burning methods. The geo-accumulation index of Cd was much higher than 5. The results of the human health risk assessment showed that non-carcinogenic risk values for 8 heavy metals (Pb, Zn, Cu, Mn, As, Cd, Cr, and Ni) by respiratory exposure were less than 1, which is within the safe range. For natural pile-up burning, the total non-carcinogenic risk values for As and Pb for children were higher than 1, indicating a non-carcinogenic risk. The carcinogenic risk values for four carcinogenic elements (As, Cd, Cr, and Ni) were less than 1.0×10-4, but still represented a low potential carcinogenic risk under exposure for long periods of time.

Preclinical pharmacokinetics of a recombinant humanized rabbit anti-VEGF monoclonal antibody in rabbits and monkeys.

TMAB001 is a humanized rabbit monoclonal antibody (mAb) designed to bind and neutralize human vascular endothelial growth factor (VEGF)-165. The purpose of the study was to investigate the pharmacokinetics (PK) and ocular tissue distribution after a single intravitreal (IVT) dose in rabbits and monkeys. Rabbits (2.5 mg/eye; n = 40) and monkeys (2.5 mg/eye; n = 12) received TMAB001 as a bilateral IVT dose. TMAB001 concentrations were measured in ocular tissues in all rabbits and monkeys by enzyme-linked immunosorbent assay (ELISA). TMAB001 and VEGF concentrations were measured in serum of monkeys by ELISA. Following a single bilateral IVT injection of TMAB001 2.5 mg/eye, the highest concentration was in vitreous humor, followed by retina and choroid, and the lowest concentration was in lens. In rabbits, TMAB001 was still detectable in ocular tissues at day 21 after single IVT dose, with the highest level in the vitreous humor and then retina, with longest t1/2 in aqueous humor and shortest t1/2 in choroid. In monkeys, tmax in serum was 43 h and t1/2 was approximately 5.5 days. Cmax in serum was much lower than that in vitreous, nearly 1/200. After IVT injection of TMAB001, total VEGF concentrations in serum and ocular tissues increased over time. VEGF concentration in retina and choroid increased over time, up to 336 h after administration. This study demonstrated that TMAB001 could reach the drug target sites-retina and choroid after a single bilateral IVT administration in rabbits and monkeys, with a long t1/2 in vitreous humor. TMAB001 also showed strong capability to neutralize VEGF. The study further confirmed that full-length antibodies can also efficiently diffuse and distribute in ocular tissues.

Recombinant humanized anti-vascular endothelial growth factor monoclonal antibody efficiently suppresses laser-induced choroidal neovascularization in rhesus monkeys.

Neovascular age-related macular degeneration, characterized by abnormal choroidal neovascularization (CNV), is a major cause of blindness worldwide. Anti-vascular endothelial growth factor (VEGF) antibodies have demonstrated significant efficacy in improving visual acuity. TMAB001 is a new recombinant humanized rabbit anti-VEGF monoclonal antibody. It presents high activities in vitro studies. In the binding affinity assay, TMAB001 exhibited a high binding capability to VEGF with an affinity constant of 10-11M. In the receptor antagonist activity assay, IC50 of TMAB001 was 0.15µg/ml. In a cell-based assay, TMAB001 inhibited VEGF165-induced HUVEC cells proliferation in a dose-dependent manner. Furthermore, in the rhesus monkey model of laser-induced CNV, results showed the growth and leakage of experimental CNV were significantly decreased with a single bilateral intravitreal injection of TMAB001, and the grade 4 lesions were complete absence in TMAB001 groups. The efficacy of TMAB001 was maintained for at least 28days. In a mice model of oxygen-induced retinopathy, the retina fluorescence leakage was reduced and the vascular morphology in retina was normalized by TMAB001 intraperitoneal administration. In conclusion, those results indicate that TMAB001 might be a potential drug candidate for wet AMD.

Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1) analog fusion protein, on CHO recombinant cells and BKS-db mice.

AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro. In vivo, body weight, food intake, non-fasting and fasting blood glucose, oral glucose tolerance test, blood glucose and insulin levels, liver histology, liver function parameters and antibody levels in BKS-db mice were investigated to evaluate the effects of GW002. Albiglutide was chosen as a positive comparator. RESULTS: Cyclic adenosine monophosphate levels were increased in a dose-dependent manner in cells. In vivo studies demonstrated that GW002 lowers non-fasting and fasting blood glucose levels and improves glucose tolerance and insulin secretion in BKS-db mice. The degree of hepatic steatosis and hepatic biochemical indexes was also decreased. In this study, the mice body weight was not reduced significantly. CONCLUSIONS: The above results showed that the efficacy of GW002 in BKS-db mice displayed a significant hypoglycemic effect, which indicated that GW002 might be a potential candidate for the treatment of T2DM.