PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.

Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1's nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures. Disruption of G4-RNA structures by lithium chloride failed to bind with FXR1, indicating its preference for G4-RNA structure containing mRNAs. Furthermore, loss-of-function of PRMT5 inhibited FXR1 methylation both in vivo and in vitro, affecting FXR1 protein stability, inhibiting RNA-binding activity and cancer cell growth and proliferation. Finally, the enhanced crosslinking and immunoprecipitation (eCLIP) analyses reveal that FXR1 binds with the G4-enriched mRNA targets such as AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1 and UBR4 and controls its mRNA expression in cancer cells. Our findings suggest that PRMT5-mediated FXR1 methylation is required for RNA/G4-RNA binding, which promotes gene expression in cancer cells. Thus, FXR1's structural characteristics and affinity for RNAs preferentially G4 regions provide new insights into the molecular mechanism of FXR1 in oral cancer cells.

Contributions of local emissions and regional background to summertime ozone in central China.

Source contributions and regional transport of maximum daily average 8-h (MDA8) O3 during a high O3 month (June 2019) in Henan province in central China are explored using a source-oriented Community Multiscale Air Quality (CMAQ) model. The monthly average MDA8 O3 exceeds ∼70 ppb in more than half of the areas and shows a clear spatial gradient, with lower O3 concentrations in the southwest and higher in the northeast. Significant contributions of anthropogenic emissions to monthly average MDA8 O3 concentrations of more than 20 ppb are predicted in the provincial capital Zhengzhou, mostly due to emissions from the transportation sector (∼50%) and in the areas in the north and northeast regions where industrial and power generation-related emissions are high. Biogenic emissions in the region only contribute to approximately 1-3 ppb of monthly average MDA8 O3. In industrial areas north of the province, their contributions reach 5-7 ppb. Two CMAQ-based O3-NOx-VOCs sensitivity assessments (the local O3 sensitivity ratios based on the direct decoupled method and the production ratio of H2O2 to HNO3) and the satellite HCHO to NO2 column density ratio consistently show that most of the areas in Henan are in NOx-limited regime. In contrast, the high O3 concentration areas in the north and at the city centers are in the VOC-limited or transition regimes. The results from this study suggest that although reducing NOx emissions to reduce O3 pollution in the region is desired in most areas, VOC reductions must be applied to urban and industrial regions. Source apportionment simulations with and without Henan anthropogenic emissions show that the benefit of local anthropogenic NOx reduction might be lower than expected from the source apportionment results because the contributions of Henan background O3 increase in response to the reduced local anthropogenic emissions due to less NO titration. Thus, collaborative O3 controls in neighboring provinces are needed to reduce O3 pollution problems in Henan effectively.

The Role of Protein Arginine Methyltransferases in DNA Damage Response.

In response to DNA damage, cells have developed a sophisticated signaling pathway, consisting of DNA damage sensors, transducers, and effectors, to ensure efficient and proper repair of damaged DNA. During this process, posttranslational modifications (PTMs) are central events that modulate the recruitment, dissociation, and activation of DNA repair proteins at damage sites. Emerging evidence reveals that protein arginine methylation is one of the common PTMs and plays critical roles in DNA damage response. Protein arginine methyltransferases (PRMTs) either directly methylate DNA repair proteins or deposit methylation marks on histones to regulate their transcription, RNA splicing, protein stability, interaction with partners, enzymatic activities, and localization. In this review, we summarize the substrates and roles of each PRMTs in DNA damage response and discuss the synergistic anticancer effects of PRMTs and DNA damage pathway inhibitors, providing insight into the significance of arginine methylation in the maintenance of genome integrity and cancer therapies.

The Roles of Post-Translational Modifications on mTOR Signaling.

The mechanistic target of rapamycin (mTOR) is a master regulator of cell growth, proliferation, and metabolism by integrating various environmental inputs including growth factors, nutrients, and energy, among others. mTOR signaling has been demonstrated to control almost all fundamental cellular processes, such as nucleotide, protein and lipid synthesis, autophagy, and apoptosis. Over the past fifteen years, mapping the network of the mTOR pathway has dramatically advanced our understanding of its upstream and downstream signaling. Dysregulation of the mTOR pathway is frequently associated with a variety of human diseases, such as cancers, metabolic diseases, and cardiovascular and neurodegenerative disorders. Besides genetic alterations, aberrancies in post-translational modifications (PTMs) of the mTOR components are the major causes of the aberrant mTOR signaling in a number of pathologies. In this review, we summarize current understanding of PTMs-mediated regulation of mTOR signaling, and also update the progress on targeting the mTOR pathway and PTM-related enzymes for treatment of human diseases.

Characteristics, sources and health risks assessment of VOCs in Zhengzhou, China during haze pollution season.

Zhengzhou is one of the most haze-polluted cities in Central China with high organic carbon emission, which accounts for 15%-20% of particulate matter (PM2.5) in winter and causes significantly adverse health effects. Volatile organic compounds (VOCs) are the precursors of secondary PM2.5 and O3 formation. An investigation of characteristics, sources and health risks assessment of VOCs was carried out at the urban area of Zhengzhou from 1st to 31st December, 2019. The mean concentrations of total detected VOCs were 48.8 ± 23.0 ppbv. Alkanes (22.0 ± 10.4 ppbv), halocarbons (8.1 ± 3.9 ppbv) and aromatics (6.5 ± 3.9 ppbv) were the predominant VOC species, followed by alkenes (5.1 ± 3.3 ppbv), oxygenated VOCs (3.6 ± 1.8 ppbv), alkyne (3.5 ± 1.9, ppbv) and sulfide (0.5 ± 0.9 ppbv). The Positive Matrix Factorization model was used to identify and apportion VOCs sources. Five major sources of VOCs were identified as vehicular exhaust, industrial processes, combustion, fuel evaporation, and solvent use. The carcinogenic and non-carcinogenic risk values of species were calculated. The carcinogenic and non-carcinogenic risks of almost all air toxics increased during haze days. The total non-carcinogenic risks exceeded the acceptable ranges. Most VOC species posed no non-carcinogenic risk during three haze events. The carcinogenic risks of chloroform, 1,2-dichloroethane, 1,2-dibromoethane, benzyl chloride, hexachloro-1,3-butadiene, benzene and naphthalene were above the acceptable level (1.0  ×  10-6) but below the tolerable risk level (1.0  ×  10-4). Industrial emission was the major contributor to non-carcinogenic, and solvent use was the major contributor to carcinogenic risks.

Characteristics of ozone pollution and the sensitivity to precursors during early summer in central plain, China.

In this study, we conducted an observation experiment from May 1 to June 30, 2018 in Zhengzhou, a major city in central China, where ground ozone (O3) pollution has become serious in recent years. The concentrations of O3 and its precursors, as well as H2O2 and meteorological data were obtained from the urban site (Yanchang, YC), suburban (Zhengzhou University, ZZU) and background sites (Ganglishuiku, GLSK). Result showed that the rates of O3 concentration exceeded Chinese National Air Quality Standard Grade II (93.3 ppbv) were 59.0%, 52.5%, and 55.7% at the above three sites with good consistency, respectively, indicating that O3 pollution is a regional problem in Zhengzhou. The daily peak O3 appeared at 15:00-16:00, which was opposite to VOCs, NOx, and CO and consistent with H2O2. The exhaustive statistical analysis of meteorological factors and chemical effects on O3 formation at YC was advanced. The high concentration of precursors, high temperature, low relative humidity, and moderately high wind speed together with the wind direction dominated by south and southeast wind contribute to urban O3 episodes in Zhengzhou. O3 formation analysis showed that reactive alkenes such as isoprene and cis-2-butene contributed most to O3 formation. The VOCs/NOx ratio and smog production model were used to determine O3-VOC-NOx sensitivity. The O3 formation in Zhengzhou during early summer was mainly under VOC-limited and transition regions alternately, which implies that the simultaneous emission reduction of alkenes and NOx is effective in reducing O3 pollution in Zhengzhou.

Spatiotemporal characterization and regional contributions of O3 and NO2: An investigation of two years of monitoring data in Henan, China.

To investigate the characteristics of ground level ozone (O3) for Henan Province, the ambient air quality monitoring data of 2015 and 2016 were analyzed. The result showed that the 8 h-max-O3 concentrations displayed a distinct seasonality, where the maximum and minimum values, averaging 140.41, 54.19 µg/m3, occurred in summer and winter, respectively. There is a significant correlation between meteorological factors and O3 concentration. The Voronoi neighborhood averaging analysis indicated that O3, temperature, and ultraviolet radiation in Henan province were decreased from northwest to southeast, while relative humidity and precipitation displayed the opposite trend. Besides meteorological factors, the chemical processes play an essential role in ozone formation. Reactions of NO, NO2 and O3 form a closed system, and the partitioning point of the OX-component (O3 + NO2) was at 40 and 80 µg/m3 for nitrogen oxide (NOX) in winter and summer, respectively, with NO2 dominating at higher NOx pollution and O3 being the major component at lower levels. The relationship between oxidant (OX = O3+NO2) and NOx concentrations were evaluated to understand the regional and local contribution of OX. It showed that high regional contribution occurred in the spring, whereas the highest local contribution lead to the summer peak of O3 observed in Zhengzhou. This present study reveals important environment impacts from the photochemical process and the meteorological conditions in the region with better understanding on the O3 characterization.

Recent development of a refined multiple air pollutant emission inventory of vehicles in the Central Plains of China.

Central Plains region of China, represented by Henan Province, is facing serious air pollution problems. Vehicular exhaust emissions had adverse impacts on the atmospheric environment. The first comprehensive and novel vehicle emission inventory for Henan Province using vehicle kilometers traveled, localized emission factors, and activity data at city-level was developed. Furthermore, 3 km × 3 km gridded emission and temporal variations were determined by using localized information. Results show that the total emissions of sulfur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), particular matter with aerodynamic diameter < 10 µm (PM10), aerodynamic diameter < 2.5 µm (PM2.5), volatile organic compounds (VOCs), VOCs-evaporation and ammonia in 2015 were 9.1, 533.4, 1190.7, 23.7, 21.6, 150.8, 31.5 and 10.4 Gg, respectively, and the emission intensities of the above pollutants were 0.05, 2.7, 6.0, 0.1, 0.1, 0.8, 0.2 and 0.05 g/km, respectively. Vehicles meeting the Primary China 1, China 3 and China 4 contributed 89.1%, 82.7%, 75.3%, 75.5%, 75.5%, 68.2%, 68.4% and 82.3% for SO2, NOx, CO, PM10, PM2.5, VOCs, VOCs-evaporation and ammonia emissions, respectively. Zhengzhou, Zhoukou, Nanyang, Luoyang, Shangqiu and Xinyang showed relatively higher emissions and contributed more than 50% of each pollutant. The spatial distribution indicated obvious characteristics of the road network, and high-level emission was concentrated in the downtown areas. Additionally, the ozone formation potential (OFP) based on the estimated speciated VOC emissions was 569.6 Gg in Henan Province. Aliphatic and aromatic hydrocarbons were the main species of VOCs, whereas olefins contributed the largest proportion of OFP, with 42.2%.

TGFß-incurred epigenetic aberrations of miRNA and DNA methyltransferase suppress Klotho and potentiate renal fibrosis.

Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not exclusively established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis. Fibrotic kidneys induced by unilateral ureteral occlusion (UUO) displayed marked Klotho suppression and the promoter hypermethylation. These abnormalities were likely due to deregulated transforming growth factor-beta (TGFß) since TGFß alone caused the similar epigenetic aberrations in cultured renal cells and TGFß blockade prevented the alterations in UUO kidney. Further investigation revealed that TGFß enhanced DNA methyltransferase (DNMT) 1 and DNMT3a via inhibiting miR-152 and miR-30a in both renal cells and fibrotic kidneys. Accordingly the blockade of either TGFß signaling or DNMT1/3a activities significantly recovered the Klotho loss and attenuated pro-fibrotic protein expression and renal fibrosis. Moreover, Klotho knockdown by RNA interferences abolished the anti-fibrotic effects of DNMT inhibition in both TGFß-treated renal cell and UUO kidney, indicating that TGFß-mediated miR-152/30a inhibitions, DNMT1/3a aberrations and subsequent Klotho loss constitute a critical regulatory loop that eliminates Klotho's anti-fibrotic activities and potentiates renal fibrogenesis. Thus, our study elaborates a novel epigenetic cascade of renal fibrogenesis and reveals the potential therapeutic targets for treating the renal fibrosis-associated kidney diseases.

Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease.

Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease. In addition to being an impressive Klotho upregulator, rhein remarkably reversed renal Klotho deficiency in adenine-treated mice. This effect was associated with significant improvement in disturbed serum biochemistry, profibrogenic protein expression, and kidney and bone damage. Further investigation of the molecular basis of Klotho loss revealed that these kidneys displayed marked inductions of DNA methyltransferase DNMT1/DNMT3a and Klotho promoter hypermethylation, whereas rhein treatment effectively corrected these alterations. The renal protective effects of rhein were largely abolished when Klotho was knocked-down by RNA interferences, suggesting that rhein reversal of Klotho deficiency is essential for its renoprotective actions. Thus, our study clarifies how rhein regulation of Klotho expression contributes to its renoprotection and brings new insights into Klotho-targeted strategy for the treatment of kidney diseases of various etiologies.

Klotho restoration via acetylation of Peroxisome Proliferation-Activated Receptor γ reduces the progression of chronic kidney disease.

Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A. This inhibition up-regulated Klotho mainly through an enhancement of PPARγ acetylation, stimulation of PPARγ binding to Klotho promoter, and PPARγ-dependent increase in Klotho transcription, with a substantial control of the regulation occurring via PPARγ acetylations on K240 and K265. Consistently trichostatin A-induced reversal of Klotho loss and renoprotective effects were abrogated in PPARγ knockout mice, supporting that PPARγ is an essential acetylation target for Klotho restoration and renal protection. Intriguingly, the kidneys of adenine-fed CKD mice displayed deregulated HDAC3 up-regulation. Selective HDAC3 inhibition effectively alleviated Klotho loss and kidney injury, whereas the protective effects were largely abolished when Klotho was knocked down by siRNA, suggesting that aberrant HDAC3 and Klotho loss are crucial components involved in the renal damage of mice with CKD. Our study identified an important signaling cascade and key components contributing to the pathogenesis of CKD. Thus, targeting Klotho loss by HDAC3 inhibition has promising therapeutic potential for the reduction of CKD progression.

Elevated fractional exhaled nitric oxide (FeNO) is a clinical indicator of uncontrolled asthma in children receiving inhaled corticosteroids.


Objective: Our study aims to explore the correlation between fractional exhaled nitric oxide (FeNO) and inhaled corticosteroids (ICS) efficacy in childhood bronchial asthma (BA). METHODS: 247 pediatric BA patients were selected and divided into 3 treatment groups based on drug therapy: treatment group 1 (seretide, n = 86), treatment group 2 (budesonide, n = 79), and treatment group 3 (salbutamol, n = 82). Another 90 healthy children were recruited as control group. FeNO, FEV1%pred, FEV1/FVC, MEF25%, MEF50% and PEF%, total serum IgE, EOS%, induced sputum EOS% and supernatant inflammatory indexes (ECP, IL-8, and TNF-α) of sputum, ECP, IL-8 and TNF-α were detected. RESULTS: Compared with pretreatment, 6 months posttreatment, FeNO, induced sputum EOS%, supernatant inflammatory indexes decreased (all p < 0.05), but pulmonary function indexes and childhood asthma control test (C-ACT) increased in treatment groups (all p < 0.05). FeNO, induced sputum EOS%, and supernatant inflammatory indexes in treatment group 1 were lower than those in treatment group 2 and 3 (all p < 0.05); total serum IgE and peripheral blood EOS% in treatment group 1 and 2 were lower but pulmonary function indexes were higher than those in treatment group 3 (all p < 0.05); according to Pearson correlation analysis, in both ICS and non-ICS groups, FeNO was positively correlated to ECP but negatively to C-ACT. CONCLUSION: ICS is effective in BA treatment, and FeNO associated with ICS efficacy is an indicator for BA intervention. FeNO combing with pulmonary function indexes had a predictive value in BA response.

Tissue distribution and functional analysis of vitellogenin-6 of Toxocara canis.

Toxocara canis is an common intestinal nematode of canids and the principal causative agent of human toxocariasis. Vitellogenin (Vg), a source of amino acids and lipids in the eggs, are considered to play an important role in embryo development of a wide range of organisms. In the present study, the transcriptional levels of Tc-vit-6 gene in male and female adult T. canis were determined by quantitative real-time PCR, which indicated high transcription of Tc-vit-6 in the intestine, reproductive tract and body wall of male and female adult T. canis. The fragment of Tc-vit-6 encoding a vWD domain, was cloned and expressed to produce a rabbit anti-TcvWD polyclonal antibody. Tissue distribution of TcVg6 was detected by immunohistochemical assays, which showed predominant distribution of TcVg6 in the tissues of intestine, as well as reproductive tract (including some of the germ cells) and musculature of male and female adult worms. Collectively, these results indicated multiple biological roles of TcVg6 apart from that in the reproduction of T. canis.

Sinomenine attenuates renal fibrosis through Nrf2-mediated inhibition of oxidative stress and TGFß signaling.

Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFß-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFß-treated kidney cells and attenuated the renal fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFß/Smad and Wnt/ß-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders.

Characterization and differential expression analysis of Toxocara canis aquaporin-1 gene.

Toxocara canis is an intestinal nematode of canids with a worldwide distribution, causing an important but neglected parasitic zoonosis in humans. Aquaporins (AQP) are a family of water channel proteins, which function as membrane channels to regulate water homeostasis. In this study, the coding sequence of aquaporin-1 gene of T. canis (Tc-aqp-1) was cloned and characterized. The obtained Tc-aqp-1 coding sequence was 933 bp in length, which predicted to encode 311 amino acids. Two conserved asparagine-proline-alanine (NPA) motifs were identified in the multiple sequence alignments. Phylogenetic analysis revealed the closest relationship between T. canis and Opisthorchis viverrini based on aquaporin-1 amino acid sequence. A structure was predicted with ligand binding sites predicted at H93, N95, N226, L94, I79, and I210 and with active sites predicted at I256 and G207. Gene Ontology (GO) annotations predicted its cellular component term of integral component of plasma membrane (GO: 0005887), molecular function term of channel activity (GO: 0015250), and biological process term of water transport (GO: 0006833). Tissue expression analysis revealed that the Tc-aqp-1 was highly expressed in the intestine of adult male. The findings of the present study provide the basis for further functional studies of T. canis aquaporin-1.

Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation.

INTRODUCTION: Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function, but the critical molecule mediating the inflammation inhibition has not been elucidated. Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating host defense against oxidative stress and inflammation-related disorders. In this study we use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory action. METHODS: We compared CORM-2's inhibiting effect on pro-inflammatory cytokine expressions (TNF-α, IL-1ß and IL-6 and iNOS) in primary peritoneal macrophages, mouse liver and brain tissues from Nrf2(+/+) and Nrf2(-/-) mice. We further assayed the inflammatory cell infiltration in both liver and brain tissues of the Nrf2(+/+) and Nrf2(-/-) mice. Finally, we examined CORM's influence on mouse mortality in a mouse sepsis model. RESULTS: Our results showed that CORM-2 dramatically inhibited the expression of pro-inflammatory cytokines in Nrf2(+/+) mice, but not in Nrf2(-/-) mice. Furthermore CORM-2 substantially decreased LPS-induced mouse mortality of Nrf2(+/+) mice, but not of Nrf2(-/-) mice. CONCLUSION: We conclude that Nrf2 is indispensable for CORM-2 inhibition of LPS-induced inflammation.

Exposure assessment, chemical characterization and source identification of PM2.5 for school children and industrial downwind residents in Guangzhou, China.

To assess the exposure doses of PM(2.5) and to investigate its chemical components for the subpopulation (i.e., school children and industrial downwind residents), simultaneous sampling of indoor and outdoor PM(2.5) was conducted at an elementary school close to traffic arteries and a residence located in the downwind area of a steel plant in metropolitan Guangzhou in 2010. Chemical components, i.e., organic carbon, elemental carbon and 6 water soluble ions were analyzed in PM(2.5). A survey was also conducted to investigate the time-activity patterns of the school children and the industrial downwind residents. Indoor and outdoor PM(2.5) were 63.2 ± 20.1 and (76.7 ± 35.8) µg/m(3) at the school, and 118.8 ± 44.7 and 125.7 ± 57.1 µg/m(3) in the community, respectively. Indoor PM(2.5) was found to be highly related to outdoor sources, and stationary sources were the significant contributors to PM(2.5) at both sites. The daily average doses of PM(2.5) for the school children at the school (D(children)) and the industrial downwind residents in the community (D(residents)) were (7.6 ± 1.9) and (36.1 ± 36.8) µg/kg-day, respectively. The daily average doses of particulate organic mass and SO(4)(2-) were the two most abundant chemical components in PM(2.5). PM(2.5) exposure for the school children was contributed by indoor and outdoor environments by 48.8 and 51.2 %, respectively; for the industrial downwind residents, the contributions were 66.0 and 34.0 %, respectively. Age and body weight were significantly and negatively correlated with D(children), while age, body weight and education level were significantly and negatively correlated with D(residents); gender was not a significant factor at both cases.

Analysis of the Class 1 Integrons, Carbapenemase Genes and Biofilm Formation Genes Occurrence in Acinetobacter baumannii Clinical Isolates.

Acinetobacter baumannii is a non-fermentative Gram-negative bacterium that can cause nosocomial infections in critically ill patients. Carbapenem-resistant A. baumannii (CRAB) has spread rapidly in clinical settings and has become a key concern. The main objective of this study was to identify the distribution of integrons and biofilm-formation-related virulence genes in CRAB isolates. A total of 269 A. baumannii isolates (219 isolates of CRAB and 50 isolates of carbapenem-sensitive A. baumannii (CSAB)) were collected. Carbapenemase genes (bla KPC, bla VIM, bla IMP, bla NDM, and bla OXA-23-like) and biofilm-formation-related virulence genes (abal, bfms, bap, and cusE) were screened with PCR. Class 1 integron was screened with PCR, and common promoters and gene cassette arrays were determined with restriction pattern analysis combined with primer walking sequencing. Whole-genome sequencing was conducted, and data were analyzed for a bla OXA-23-like-negative isolate. All 219 CRAB isolates were negative for bla KPC, bla VIM, bla IMP, and bla NDM, while bla OXA-23-like was detected in 218 isolates. The detection rates for abal, bfms, bap, and cusE in 219 CRAB were 93.15%, 63.93%, 88.13%, and 77.63%, respectively. Class 1 integron was detected in 75 CRAB (34.25%) and in 3 CSAB. The single gene cassette array aacA4-catB8-aadA1 with relatively strong PcH2 promoter was detected in class 1 integrons. The bla OXA-23-like-negative CRAB isolate was revealed to be a new sequence type (Oxford 3272, Pasteur 2520) carrying bla OXA-72, bla OXA-259, and bla ADC-26. In conclusion, bla OXA-23-like was the main reason for CRAB's resistance to carbapenems. A new (Oxford 3272, Pasteur 2520) CRAB sequence type carrying the bla OXA-72, bla OXA-259, and bla ADC-26 was reported.

Atmospheric H2O2 during haze episodes in a Chinese megacity: Concentration, source, and implication on sulfate production.

Atmospheric hydrogen peroxide (H2O2), as an important oxidant, plays a key role in atmospheric chemistry. To reveal its characteristics in polluted areas, comprehensive observations were conducted in Zhengzhou, China from February 22 to March 4, 2019, including heavy pollution days (HP) and light pollution days (LP). High NO concentrations (18 ± 26 ppbv) were recorded in HP, preventing the recombination reaction of two HO2• radicals. Surprisingly, higher concentrations of H2O2 were observed in HP (1.5 ± 0.6 ppbv) than those in LP (1.2 ± 0.6 ppbv). In addition to low wind speed and relative humidity, the elevated H2O2 in HP could be mainly attributed to intensified particle-phase photoreactions and biomass burning. In terms of sulfate formation, transition-metal ions (TMI)-catalyzed oxidation emerged as the predominant oxidant pathway in both HP and LP. Note that the average H2O2 oxidation rate increased from 3.6 × 10-2 in LP to 1.1 × 10-1 µg m-3 h-1 in HP. Moreover, the oxidation by H2O2 might exceed that of TMI catalysis under specific conditions, emerging as the primary driver of sulfate formation.

The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.