EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.

[Establishment of High-Resolution Emissions Inventory in Wuhai and Its Application in Exploring the Causes of Ozone Pollution].

Wuhai is a typical coking industrial base including three industrial parks within its jurisdiction. The emission amount of air pollutants is considerable here, and O3 pollution has become serious in recent years. Clarifying the air pollutant emission characteristics and exploring the formation mechanism of O3 are the basis for objectively understanding the O3 pollution and formulating scientific prevention and control measures. This study established the high-resolution emission inventory of Wuhai in 2018 (HEI-WH18) based on the "coefficient method," evaluated the applicability and accuracy of HEI-WH18 using the WRF-Chem model, and explored the causes of O3 pollution in summer using WRF-Chem diagnosis module output. The HEI-WH18 showed that the total emissions amount of SO2, NOx, CO, PM10, PM2.5, VOCs, NH3, BC, and OC were 65943, 40934, 172867, 159771, 47469, 69191, 1407, 1491, and 1648 t·a-1, respectively. HEI-WH18 could capture the variation and magnitude of O3 and its precursors better than the MEIC, which was suitable for the O3 simulation and source analysis in summer. From the perspective of spatial distribution, Haibowan was a high-value area of O3 during the daytime, and the three industrial parks were low-value areas of O3 and high-value areas of NO2 during the daytime and nighttime. The spatial distribution characteristics of CO were consistent with the spontaneous combustion of coal and coal gangue sources. According to the diagnostic analysis of two O3 pollution processes, the O3 increase in the upper boundary layer was mainly related to the advection transport and chemical process, and it was caused by vertical mixing and the advection transport process in the lower boundary layer. The contribution of the chemical process in the lower boundary layer was complicated, and its positive contribution played a role in maintaining a high O3 concentration, whereas its negative contribution combined with advection transport resulted in the final dissipation of O3 pollution.

[Nonlinear Response Characteristics and Control Scheme for Ozone and Its Precursors Based on Orthogonal Experimental Methods].

There is a highly nonlinear relationship between ozone concentrations and its precursor emissions in different regions and at different times, which makes developing effective prevention and control measures difficult. An orthogonal experimental method was introduced to assess the influence of ozone precursors and their interactions on ozone formation, clarify the sensitivity of ozone generation, and propose an optimal control scheme. Based on the WRF-Chem air quality model and an emission inventory of air pollutants in Wuhai City in 2018, this study used an ozone pollution event in the Haibowan urban area (August 17 to 20 2018) to investigate the nonlinear response of ozone formation to its precursors. The orthogonal experiment shows that NOx, VOCs interactions with CO, CO, and interactions between pollutants and meteorological factors are the main factors affects ozone concentrations in the Haibowan urban area. Ozone generation was most sensitive to NOx concentrations during the hours 12:00-18:00 when standard values were exceeded. The ozone concentrations decreased significantly by 12.6 µg·m-3 (7.8%) as NOx, VOCs, and CO were reduced by 60%, 30%, and 30%, respectively. Through the analysis of chemical reaction mechanisms, it is concluded that VOCs and CO affect the photochemical reaction by reacting with·OH, HO2·and other free radicals, which causes the significant interaction between VOCs and CO in the generation of ozone. This method provides a new approach for researching the nonlinear response of ozone formation to its precursors and for proposing ozone pollution control schemes.

[Exploring Characteristics and Causes of Summer Ozone Pollution Based on Process Analysis in Wuhai].

In recent years, summer O3 pollution has become more severe in Wuhai, where the terrain is complex and industrial parks are densely distributed. However, the characteristics and formation mechanisms of this pollution have not yet been investigated and remain unclear. Analyzing the variation and formation mechanisms of O3 is crucial to the prevention and control of air pollution in this region. By analyzing characteristics and using a WRF-CMAQ model to simulate three O3 pollution periods in Wuhai from June to August 2018, this study explored the causes of O3 pollution based on in-depth process analysis, and the effects of regional transportation and local photochemical reaction on O3 were also discussed. The diurnal variation of ozone exhibited a single-peak distribution, and near-surface O3 was positively correlated with short-wave radiation and temperature, and negatively correlated with relative humidity. The areas of Shizuishan in Ningxia and the Ulanbuhe desert exhibited high O3 values during the day, while the three industrial parks in Wuhai exhibited low values during both the day and night. Process analysis showed that transportation, chemical processes, and their relative magnitudes had a significant impact on O3. Local photochemical reactions and transport during the pollution period in June and July led to an obvious increase in O3, while the impact of chemical processes was about twice as large as that of transport. The increase of O3 in August was mainly caused by transport. Further decomposition of the transportation effect showed that transportation in the south and northwest directions had a remarkable effects on the increase of O3. Together with the emission of O3 precursors, the main sources of transportation were the Yinchuan, Shizuishan, and Bayannaoer regions. Therefore, Wuhai and neighboring cities should strengthen regional joint prevention and control by jointly formulating and implementing control measures for air pollution to reduce the impact of regional transmission on O3.

[Establishment of a High-resolution Anthropogenic Emission Inventory and Its Evaluation Using the WRF-Chem Model for Lanzhou].

City-scale high-resolution anthropogenic emission inventories are an important tool for ambient air quality forecasting and early warning, the analysis of underlying causes, and policy making. At present, city-scale anthropogenic emissions inventories for use in air quality models are scarce for West China. By studying the literature on emission inventories, this paper establishes a city-scale anthropogenic emission inventory for Lanzhou (HEI-LZ16) as the basis for an air quality model. The weather research and forecasting with chemistry (WRF-Chem) model was used to evaluate the applicability of the emission inventory at different resolutions in Lanzhou. The results showed that the emission amounts of SO2, NOx, CO, NH3, VOCs, PM10, PM2.5, BC, and OC in Lanzhou were 25642, 53998, 319003, 10475, 35289, 49250, 19822, 2476, and 1482 t·a-1 in 2016,respectively. Compared with the simulation scenario of multi-resolution emission inventory for China (MEIC), normalized mean error (NME) of O3 and PM2.5 under the HEI-LZ16 scenario decreased by 140.2% and 28.8%, respectively. The HEI-LZ16 inventory is more suitable for application in air pollution research in Lanzhou, which was verified by the WRF-Chem model and the observational data. The spatiotemporal distributions of PM2.5 and O3 were also analyzed using the HEI-LZ16 scenario. The ozone concentration of the maximum daily 8-h average (MDA8) in Lanzhou was low in urban areas and high in the suburbs during winter and spring, and high in the west of the urban valley and its downwind areas during summer and autumn. MDA8 in summer and autumn was influenced by easterly winds and photochemical reactions. In winter, ozone concentrations in urban areas are suppressed by NOx emissions but the concentration decreases. High PM2.5 concentrations are mainly concentrated within the Yellow River Valley. This study shows that there is a pollutant transmission channel along the western side of the Baiyin-Lanzhou Yellow River Valley, which has a greater impact on the ambient air quality in Lanzhou.

Effect of aldehyde dehydrogenase 2 gene polymorphism on hemodynamics after nitroglycerin intervention in Northern Chinese Han population.

BACKGROUND: Nitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population. METHODS: This study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes. RESULTS: Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05). CONCLUSION: ALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

[Some thoughts of the comparison of risk based soil environmental standards between different countries].

Risk-based soil environmental standard is one of the important aspects in contaminated soil management which have already been widely used in many countries. However, because of diversity in geographical, biological, social-cultural, regulatory and scientific aspects among each country, there are great distinctions on both titles and values of these soil environmental standards between different countries. Risk-based soil environmental standards and derivation process were introduced and compared in detail. The variability was analyzed and explained through the comparison of sensitivity risk receptors, land utilizations and pathways of exposure among these countries. We suggest that the risk-based soil environmental standards among the developed countries could be classified as target value, screening value and intervention value, which aim to protect soil for sustainable development in the future, to determine whether there is potential unacceptable risk to specified acceptors, and whether further counter-actions should be conducted, respectively. At last, risk assessment of contaminated soils and establishment of risk-based soil environmental standards in China was proposed.

[Characterizing the plant uptake factor of As, Cd and Pb for rice and wheat cereal].

The statistical characteristics of plant uptake factor (PUF) of As, Cd and Pb for rice/wheat cereal were analyzed and summarized based on collected data in China. The data were selected and distinguished between field investigation and glasshouse experiment in which metal salts were added to clean soils as grown media. Results showed that the PUF median and range of As, Cd and Pb for rice cereal were 0.026 (0.004-0.090), 0.150 (0.014-1.470), 0.005 (0.001-0.031) and 0.010 (0.003-0.033), 0.360 (0.056-1.700), 0.002 (0.001-0.019) for field investigation and salt added experiment respectively. The PUF median and range of As, Cd and Pb for wheat cereal were 0.010 (0.001-0.110), 0.190 (0.030-2.110), 0.017 (0.001-0.075) and 0.010 (0.003-0.028), 0.150 (0.055-0.730), 0.001 (0.001-0.014) for field investigation and salt added experiment respectively. Significant PUF distribution differences were found between field investigation and salt added experiment. PUF provided not exactly predictive ability of metal uptake by crops since the PUF values were influenced by a variety of factors including the soil contamination levels, basic soils characteristics, the cultivation of the crops and other environmental conditions. However, the ln (PUF) followed Gaussian distribution (R2 = 0.38-0.94) which is useful for general risk assessment and soil benchmark derivation of contaminated croplands. Use of these statistical models is restricted to the range of data they have been derived, as extrapolation outside this range is often unreliable. Soil properties and surrounding environment of the crops should also be in accordance with the conditions PUF derived.

[Development of lead benchmarks for soil based on human blood lead level in China].

Lead benchmarks for soil are mainly established based on blood lead concentration of children. This is because lead plays a dramatically negative role in children's cognitive development and intellectual performance and thus soil lead has been concerned as main lead exposure source for children. Based on the extensively collection of domestic available data, lead levels in air, drinking water are 0.12-1.0 microg x m(-3) and 2-10 microg x L(-1); ingestion of lead from food by children of 0-6 years old is 10-25 microg x d(-1); geometric mean of women blood lead 1concentration of child bearing age is 4.79 microg x dL(-1), with 1.48 GSD. Lead benchmarks for soil were calculated with the Integration Exposure Uptake Biokinetic Model (IEUBK) and the Adult Lead Model (ALM). The results showed the lead criteria values for residual land and commercial/industrial land was 282 mg x kg(-1) and 627 mg x kg(-1) respectively, which was slightly lower compared with U.S.A. and U.K. Parameters sensitivity analysis indicated that lead exposure scenario of children in China was significantly different from children in developed countries and children lead exposure level in China was obviously higher. Urgent work is required for the relationship studies between lead exposure scenario and blood lead level of children and establishment of risk assessment guideline of lead contaminated soil based on human blood lead level.