Genetic polymorphism of CYP2A6 is one of the potential factors determining tobacco-related cancer risk

While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.

Spatial distribution and potential poverty-returning factors of former poverty-stricken villages in the Liangshan Mountains,China

Remote mountainous villages are at risk of falling back into poverty,despite having been lifted out of extreme poverty.However,there has been a lack of focus on the factors contributing to povertyreturn in these villages,which making it difficult to understand the risks and their underlying causes.This study investigates the spatial distribution of 546 key assistance villages(KAVs)in the Liangshan mountainous region,a former poverty-stricken area,using the average nearest neighbor(ANN)and kernel density estimation(KDE)methods.Linear regression and geographically weighted regression(GWR)models are then employed to analyze the relationship between the KAVs'economy and potential povertyreturning factors.The results show that KAVs are primarily located in elevation ranges of 1800-2500 m(31.87%),with slopes of 6°-15°(42.67%)and 2-3 km from the township(28.94%).The distribution of KAVs exhibits distinct spatial clustering,forming four gathering areas.Several factors impact the KAVs'economy positively,including the normalized difference vegetation index(NDVI),built-up area,grassland,and education facilities,while elevation has a negative effect.The built-up area has the most critical impact on the rural economy,followed by NDVI and elevation.Additionally,education facilities and grassland areas also have significant effects.The study suggests promoting the Ex-situ Poverty Alleviation Relocation Program(ESPARP)and increasing rural built-up areas,grasslands,and educational facilities as practical measures for preventing poverty return and promoting economic development promotion in remote mountain villages.

Interferon beta(IFN-β) treatment exerts potential neuroprotective effects through neurotrophic factors and novel neurotensin/neurotensin high affinity receptor 1 pathway

Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.

Exploiting epidemiological data to understand the epidemiology and factors that influence COVID-19 pandemic in Libya

There were only 75 confirmed cases of coronavirus disease 2019(COVID-19)reported in Libya by the National Center for Disease Control during the first two months following the first confirmed case on 24 March 2020.However,there was dramatic increase in positive cases from June to now;as of 19 November 2020,approximately 357940 samples have been tested by reverse transcription polymerase chain reaction,and the results have revealed a total number of 76808 confirmed cases,47587 recovered cases and 1068 deaths.The case fatality ratio was estimated to be 1.40%,and the mortality rate was estimated to be 15.90 in 100000 people.The epidemiological situation markedly changed from mid-July to the beginning of August,and the country proceeded to the cluster phase.COVID-19 has spread in almost all Libyan cities,and this reflects the high transmission rate of the virus at the regional level with the highest positivity rates,at an average of 14.54%.Apparently,there is an underestimation of the actual number of COVID-19 cases due to the low testing capacity.Consequently,the Libyan health authority needs to initiate a large-scale case-screening process and enforce testing capacities and contact testing within the time frame,which is not an easy task.Advisably,the Libyan health authority should improve the public health capacities and conduct strict hygienic measures among the societies and vaccinate as many people against COVID-19 to minimize both the case fatality ratio and socio-economic impacts of the pandemic in Libya.

The Openness Degree Study of the Jiaoshiba Shale Gas, Sichuan Basin, China–Potential Factor Responsible for Reversed Isotope Series

Objective Reversed alkane δ;C and δ;H values in many prolific shale plays all over the world have aroused much attention in the study of the formation mechanism of reversed isotope series in alkanes in the past few years（Zou Caineng et al., 2016）. Although many researchers have put forward different hypotheses, the mechanism has not been well understood yet. The openness degree of oil and gas system

The effects of nitrogen fertilizer application on methane and nitrous oxide emission/uptake in Chinese croplands

The application of nitrogen（N） fertilizer to increase crop yields has a significant influence on soil methane（CH_4） and nitrous oxide（N_2O） emission/uptake.A meta-analysis was carried out on the effect of N application on（i） CH_4 emissions in rice paddies,（ii） CH_4 uptake in upland fields and（iii） N_2O emissions.The responses of CH_4 emissions to N application in rice paddies were highly variable and overall no effects were found.CH_4 emissions were stimulated at low N application rates（〈100 kg N ha^（-1）） but inhibited at high N rates（〉200 kg N ha^（-1）） as compared to no N fertilizer（control）.The response of CH_4 uptake to N application in upland fields was 15%lower than control,with a mean CH_4 uptake factor of-0.001 kg CH_4-C kg^（-1） N.The mean N_2O emission factors were 1.00 and 0.94%for maize（Zea mays） and wheat（Triticum aestivum）,respectively,but significantly lower for the rice（Oryza sativa）（0.51%）.Compared with controls,N addition overall increased global warming potential of CH_4 and N_2O emissions by 78%.Our result revealed that response of CH_4 emission to N input might depend on the CH_4concentration in rice paddy.The critical factors that affected CH_4 uptake and N_2O emission were N fertilizer application rate and the controls of CH_4 uptake and N_2O emission.The influences of application times,cropping systems and measurement frequency should all be considered when assessing CH_4 and N_2O emissions/uptake induced by N fertilizer.

Pigment epithelium-derived factor protects retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction

AIM： To investigate the potential of pigment epitheliumderived factor（PEDF） to protect the immortalized rat retinal ganglion cells-5（RGC-5） exposed to Co Cl2-induced chemical hypoxia. METHODS： After being differentiated with staurosporine（SS）, RGC-5 cells were cultured in four conditions： control group cells cultured in Dulbecco ＇s modified eagle medium（DMEM） supplemented with 10% fetal bovine serum, 100 μmol/m L streptomycin and penicillin（named as normal conditions）; hypoxia group cells cultured in DMEM containing 300 μmol/m L Co Cl2; cells in the group protected by PEDF were first pretreated with 100 ng/m L PEDF for 2h and then cultured in the same condition as hypoxia group cells; and PEDF group cells that were cultured in the presence of 100 ng/m L PEDF under normal conditions. The cell viability was assessed by MTT assay, the percentage of apoptotic cells was quantified using Annexin V-FITC apoptosis kit, and intra-cellar reactive oxygen species（ROS） was measured by dichloro-dihydro-fluorescein diacetate（DCFH-DA） probe. The mitochondria-mediated apoptosis was also examined to further study the underlying mechanism of the protective effect of PEDF. The opening of mitochondrial permeability transition pores（m PTPs） and membrane potential（Δψm） were tested as cellular adenosine triphosphate（ATP） level and glutathione（GSH）. Also, the expression and distribution of Cyt C and apoptosis inducing factor（AIF） were observed.RESULTS： SS induced differentiation of RGC-5 cells resulting in elongation of their neurites and establishing contacts between outgrowths. Exposure to 300 μmol/m L Co Cl2 triggered death of 30% of the total cells in cultures within 24 h. At the same time, pretreatment with 100 ng/m L PEDF significantly suppressed the cell death induced by hypoxia（P〈0.05）. The apoptosis induced by treatment of Co Cl2 was that induced cell death accompanied with increasing intracellar ROS and decreasing GSH and ATP level. PEDF pretreatment suppressed these effects（P〈0.05）. Additionally, PEDF treatment inhibited the opening of m PTPs and suppressed decreasing of Δψm in RGC-5 cells, resulting in blocking of the mitochondrial apoptotic pathway.CONCLUSION： Pretreatment of RGC-5 cells with 100 ng/m L PEDF significantly decreases the extent of apoptosis. PEDF inhibits the opening of m PTPs and suppresses decreasing of Δψm. Moreover, PEDF also reduces ROS production and inhibits cellular ATP level＇s reduction. Cyt C and AIF activation in PEDF-pretreated cultures are also reduced. These results demonstrate the potential for PEDF to protect RGCs against hypoxic damage in vitro by preventing mitochondrial dysfunction.

Prevalence and Factors Associated with Female Sexual Dysfunction in Beijing, China

Background： Female sexual dysfunction （FSD） is a highly prevalent and often underestimated problem. However, large-scale, population-based epidemiological surveys of FSD are scarce in China. The present study was conducted to evaluate the prevalence and the potential risk factors of FSD across a selection of social groups in Beijing, China, based on the Female Sexual Function Index （FSFI）. Methods： A cross-sectional study based on the multiple-stage cluster sampling was performed with adult women throughout the Dongcbeng and Shunyi districts of Beijing. The Chinese version of FSFI was used, as well as questions on demographic characteristics, the disease-related context, and social relationships. Results： A total of 6000 consecutive women entered this study, with an actual response from 5024 women, corresponding to a response rate of 83.7%. A total of 4697 （78.3%） questionnaires were effective. The prevalence of adult FSD in Beijing was 2973 （63.3%） using a score of 26.55 as the boundary value, whereas the total mean FSFI score was 23.92 ~ 6.37. However, 1423 （30.3%） women did not seek help. By multivariate logistic regression analysis, the possible potential risk factors included age （odds ratio [OR] = 1.051 ）, dissatisfaction with the spouse＇s sexual ability （OR = 3.520）, poor marital affection （OR = 2.087）, spouse sexual difficulties （OR = 1.720）, dissatisfaction with married life （OR = 1.476）, living in a rural area （OR = 1.292）, chronic pelvic pain （OR = 1.261）, chronic disease （OR = 1.534）, previous pelvic surgery （OR = 1.605）, vaginal delivery （OR = 2.285）, lower education （OR = 3.449） and postmenopausal （OR = 3.183）. Conclusions： As suggested by the FSFI scores, female sexual problems are highly prevalent in Beijing. Dissatisfaction with the spouse＇s sexual ability, poor marital affection, sexual difficulties of the spouse, dissatisfaction with the marriage, rural life, CPP, and postmenopausal were conceivable risk factors for FSD in Beijing women.

Emission factors of polycyclic aromatic hydrocarbons from domestic coal combustion in China

Domestic coal stove is widely used in China, especially for countryside during heating period of winter, and polycyclic aromatic hydrocarbons （PAHs） are important in flue gas of the stove. By using dilution tunnel system, samples of both gaseous and particulate phases from domestic coal combustion were collected and 18 PAH species were analyzed by GC-MS. The average emission factors of total 18 PAH species was 171.73 mg/kg, ranging from 140.75 to 229.11 mg/kg for bituminous coals, while was 93.98 mg/kg, ranging from 58.48 to 129.47 mg/kg for anthracite coals. PAHs in gaseous phases occupied 95% of the total of PAHs emission of coal combustion. In particulate phase, 3-ring and 4- ring PAHs were the main components, accounting for 80% of the total particulate PAHs. The total toxicity potency evaluated by benzo[a]pyrene-equivalent carcinogenic power, sum of 7 carcinogenic PAH components and 2,3,7,8-tetrachlorodibenzodioxin had a similar tendency. And as a result, the toxic potential of bituminous coal was higher than that of anthracite coal. Efficient emission control should be conducted to reduce PAH emissions in order to protect ecosystem and human health.

Heterogeneity analysis of the role of film box office revenue factors:Based on quantile regression analysis

In this paper I apply the Quantile Regression model that suits for the different contribution of the attributes surrounding different levels of film revenues.The regression coefficients from this model reflects the correlation between the film revenue and the various attributes(production budget,popularity,runtime,vote average and vote count).The empirical analysis result shows that QR coefficients vary across different intervals of film revenue.This implies that the size of the effect for the influencing factors differ between profitability quantiles of films.

Distribution and assessment of heavy metals in the surface sediment of Yellow River, China

Large amounts of heavy metals discharged by industrial cities that are located along the middle reach of Yellow River, China have detrimental impacts on both the ecological environment and human health. In this study, fourteen surface sediment samples were taken in the middle reach of the Yellow River. Contents of Zn, Pb, Ni, Cu, Cr, Cd, As were measured, and the pollution status was assessed using three widely used pollution assessment methods, including the single factor index method, Nemerow pollution index method and potential ecological risk index. The concentrations of the studied heavy metals followed the order： Zn 〉 Cr 〉 Cu 〉 Ni 〉 Pb 〉 As 〉 Cd. Nearly 50% of sites had Cu and Cr accumulation. The concentration of Cu at the Yiluo River exceeded the secondary standard value of the Environmental quality standard for soils. Comparison of heavy metal concentrations between this study and other selected rivers indicated that Cu and Cr may be the major pollutants in our case. The single factor index indicated that many samples were at high levels of pollution for Cu and Cd; the Nemerow pollution index indicated that the Yihe River, Luohe River, Yiluo River and Huayuankou were polluted. According to the results of potential ecological risk assessment, Cd in the tributaries of Luo River, Yihe River,and Yiluo River showed high risk toward the ecosystem and human health, Cd in Huanyuankou and Cu in Yiluo River showed a middle level of risk and other samples were at a low level of risk.

Characteristics of particulate-bound polycyclic aromatic hydrocarbons emitted from industrial grade biomass boilers

Polycyclic aromatic hydrocarbons（PAHs） are carcinogenic or mutagenic and are important toxic pollutants in the flue gas of boilers. Two industrial grade biomass boilers were selected to investigate the characteristics of particulate-bound PAHs： one biomass boiler retro-fitted from an oil boiler（BB1） and one specially designed（BB2） biomass boiler. One coal-fired boiler was also selected for comparison. By using a dilution tunnel system, particulate samples from boilers were collected and 10 PAH species were analyzed by gas chromatography–mass spectrometry（GC–MS）. The total emission factors（EFs） of PAHs ranged from 0.0064 to0.0380 mg/kg, with an average of 0.0225 mg/kg, for the biomass boiler emission samples. The total PAH EFs for the tested coal-fired boiler were 1.8 times lower than the average value of the biomass boilers. The PAH diagnostic ratios for wood pellets and straw pellets were similar.The ratio of indeno（1,2,3-cd）pyrene/[indeno（1,2,3-cd）pyrene ＋ benzo（g,h,i）perylene] for the two biomass boilers was lower than those of the reference data for other burning devices, which can probably be used as an indicator to distinguish the emission of biomass boilers from that of industrial coal-fired boilers and residential stoves. The toxic potential of the emission from wood pellet burning was higher than that from straw pellet burning, however both of them were much lower than residential stove exhausts.

On-board measurements of gaseous pollutant emission characteristics under real driving conditions from light-duty diesel vehicles in Chinese cities

A total of 15 light-duty diesel vehicles（LDDVs） were tested with the goal of understanding the emission factors of real-world vehicles by conducting on-board emission measurements. The emission characteristics of hydrocarbons（HC） and nitrogen oxides（NOx） at different speeds, chemical species profiles and ozone formation potential（OFP） of volatile organic compounds（VOCs） emitted from diesel vehicles with different emission standards were analyzed. The results demonstrated that emission reductions of HC and NOxhad been achieved as the control technology became more rigorous from Stage I to Stage IV. It was also found that the HC and NOxemissions and percentage of O2 dropped with the increase of speed, while the percentage of CO2 increased. The abundance of alkanes was significantly higher in diesel vehicle emissions, approximately accounting for 41.1%–45.2%, followed by aromatics and alkenes. The most abundant species were propene,ethane, n-decane, n-undecane, and n-dodecane. The maximum incremental reactivity（MIR）method was adopted to evaluate the contributions of individual VOCs to OFP. The results indicated that the largest contributors to O3 production were alkenes and aromatics, which accounted for 87.7%–91.5%. Propene, ethene, 1,2,4-trimethylbenzene, 1-butene, and1,2,3-trimethylbenzene were the top five VOC species based on their OFP, and accounted for 54.0%-64.8% of the total OFP. The threshold dilution factor was applied to analyze the possibility of VOC stench pollution. The majority of stench components emitted from vehicle exhaust were aromatics, especially p-diethylbenzene, propylbenzene, m-ethyltoluene, and p-ethyltoluene.

Structure-Based Prediction of Transcription Factor Binding Sites

Transcription Factors（TFs） are a very diverse family of DNA-binding proteins that play essential roles in the regulation of gene expression through binding to specific DNA sequences. They are considered as one of the prime drug targets since mutations and aberrant TF-DNA interactions are implicated in many diseases.Identification of TF-binding sites on a genomic scale represents a critical step in delineating transcription regulatory networks and remains a major goal in genomic annotations. Recent development of experimental high-throughput technologies has provided valuable information about TF-binding sites at genome scale under various physiological and developmental conditions. Computational approaches can provide a cost-effective alternative and complement the experimental methods by using the vast quantities of available sequence or structural information. In this review we focus on structure-based prediction of transcription factor binding sites. In addition to its potential in genomescale predictions, structure-based approaches can help us better understand the TF-DNA interaction mechanisms and the evolution of transcription factors and their target binding sites. The success of structure-based methods also bears a translational impact on targeted drug design in medicine and biotechnology.