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1.
Sci Adv ; 8(49): eadd8928, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36475791

RESUMO

BRD4 functions as an epigenetic reader and plays a crucial role in regulating transcription and genome stability. Dysregulation of BRD4 is frequently observed in various human cancers. However, the molecular details of BRD4 regulation remain largely unknown. Here, we report that PRMT2- and PRMT4-mediated arginine methylation is pivotal for BRD4 functions on transcription, DNA repair, and tumor growth. Specifically, PRMT2/4 interacts with and methylates BRD4 at R179, R181, and R183. This arginine methylation selectively controls a transcriptional program by promoting BRD4 recruitment to acetylated histones/chromatin. Moreover, BRD4 arginine methylation is induced by DNA damage and thereby promotes its binding to chromatin for DNA repair. Deficiency in BRD4 arginine methylation significantly suppresses tumor growth and sensitizes cells to BET inhibitors and DNA damaging agents. Therefore, our findings reveal an arginine methylation-dependent regulatory mechanism of BRD4 and highlight targeting PRMT2/4 for better antitumor effect of BET inhibitors and DNA damaging agents.


Assuntos
Neoplasias , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Arginina , Fatores de Transcrição/genética , Reparo do DNA , DNA , Cromatina , Proteína-Arginina N-Metiltransferases/genética , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Ciclo Celular/genética
2.
Cancers (Basel) ; 14(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36230643

RESUMO

PURPOSE: The stimulator of interferon genes (STING) pathway plays a crucial role in antitumor immunity, and it is strictly regulated by many types of post-translational modifications. However, the contribution of acetylation involved in the regulation of STING to endometrial tumorigenesis remains unclear. METHODS: We attempted to identify the key role of STING in endometrial carcinoma (EC) tissue and cell lines and explore its epigenetic regulation mechanism by HDACs that are critically involved in EC. We used IHC and qRT-PCR to detect the protein level and mRNA level of STING expression in endometrial carcinoma tissues, then explored the potential role of STING in tumor proliferation and apoptosis by CCK8 and flow cytometry, and identified the STING effect in the tumorigenicity by a mouse xenograft assay. We explored the possible relationship of acetylation alteration in STING regulation by ChIP analysis and Co-IP, and we knocked out STING in ECC1 and Ishikawa cells using CRISPR-Cas9 to further confirm the critical role of STING restoration induced by HDAC3 inhibitor RGFP-966 in the proliferation and apoptosis. RESULTS: We found that STING expression was largely decreased and worked as an important regulator of cell proliferation and apoptosis; either activated or overexpressed STING, with both pharmacological and genetic approaches, largely blocked cell proliferation and induced apoptosis in EC. Moreover, STING expression was deregulated by both ß-estradiol and HDAC3. Mechanically, we determined that HDAC3 can interact with ß-estradiol-ERα and induce deacetylation of histone 3 lysine 4 at the STING promoter, thereby decreasing STING expression. Inhibition of HDAC3 increased STING expression, thereby inhibiting tumorigenesis. CONCLUSION: This study reveals a novel molecular mechanism by which HDAC3 inhibits STING transcription via ß-estradiol-ERα and provides a promising therapy (a combination of HDAC and STING) for combating endometrial cancer.

3.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077176

RESUMO

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.


Assuntos
Histonas , Proteína-Arginina N-Metiltransferases , Arginina/metabolismo , Dano ao DNA , Histonas/metabolismo , Metilação , Processamento de Proteína Pós-Traducional , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo
4.
Life (Basel) ; 12(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36013330

RESUMO

Embryonic stem cells (ESCs) are a type of cells capable of self-renewal and multi-directional differentiation. The self-renewal of ESCs is regulated by factors including signaling pathway proteins, transcription factors, epigenetic regulators, cytokines, and small molecular compounds. Similarly, non-coding RNAs, small RNAs, and microRNAs (miRNAs) also play an important role in the process. Functionally, the core transcription factors interact with helper transcription factors to activate the expression of genes that contribute to maintaining pluripotency, while suppressing the expression of differentiation-related genes. Additionally, cytokines such as leukemia suppressor factor (LIF) stimulate downstream signaling pathways and promote self-renewal of ESCs. Particularly, LIF binds to its receptor (LIFR/gp130) to trigger the downstream Jak-Stat3 signaling pathway. BMP4 activates the downstream pathway and acts in combination with Jak-Stat3 to promote pluripotency of ESCs in the absence of serum. In addition, activation of the Wnt-FDZ signaling pathway has been observed to facilitate the self-renewal of ESCs. Small molecule modulator proteins of the pathway mentioned above are widely used in in vitro culture of stem cells. Multiple epigenetic regulators are involved in the maintenance of ESCs self-renewal, making the epigenetic status of ESCs a crucial factor in this process. Similarly, non-coding RNAs and cellular energetics have been described to promote the maintenance of the ESC's self-renewal. These factors regulate the self-renewal and differentiation of ESCs by forming signaling networks. This review focused on the role of major transcription factors, signaling pathways, small molecular compounds, epigenetic regulators, non-coding RNAs, and cellular energetics in ESC's self-renewal.

5.
Huan Jing Ke Xue ; 43(6): 2947-2956, 2022 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-35686764

RESUMO

Based on air quality station data and satellite remote sensing data, the interannual variation characteristics and seasonal variation trends of near-surface ozone (O3) in Henan province were studied, and the variation in O3 sensitivity was analyzed. The results showed that the O3 concentration near the surface of Henan province increased first and then decreased from 2015 to 2020. The highest O3 concentration was found in 2018, and the annual mean of the maximum daily 8 h moving mean (MDA8) of O3 was 110.70 µg·m-3. The difference in MDA8 values among different stations gradually decreased. From 2015 to 2020, the average monthly MDA8 in Henan province showed an upward trend, with a growth rate of 2.46 µg·(m3·a)-1. According to the MK trend test, except for in Luohe, Nanyang, and Pingdingshan, the rising trend in other cities was significant (P<0.05). The concentration of MDA8 in the four seasons also showed an increasing trend during the 6 years as follows:autumn (19.31%)>winter (17.09%)>spring (16.82%)>summer (7.24%). From 2015 to 2019, the high value of tropospheric NO2 was concentrated in the northwest of Henan province, and the concentration showed a decreasing trend with a decreasing rate of 0.34×1015 molecules·(cm2·a)-1, whereas the tropospheric HCHO showed a slow rising trend with an annual growth rate of 0.19×1015 molecules·(cm2·a)-1, with a higher concentration in the northern urban area. The O3 sensitivity control area from 2015 to 2019 showed that most of the eastern part of Henan province belonged to the VOCs limited category.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental/métodos , Ozônio/análise , Estações do Ano
6.
Huan Jing Ke Xue ; 43(4): 1777-1787, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393801

RESUMO

To explore the emission characteristics of volatile organic compounds (VOCs) from vehicular exhaust sources and evaporative sources with ethanol gasoline (E10) as the main fuel, VOCs sampling campaigns were carried out in the north third ring tunnel of Zhengzhou city for two consecutive weeks in December 2019. In addition, the characteristics of traffic flow and environmental information were also monitored in the tunnel. Firstly, 106 VOCs were quantified using gas chromatography/mass spectrometry (GC/MS), and then source apportionment of VOCs in the tunnel was carried out using a positive matrix factorization (PMF5.0)-chemical mass balance (CMB8.2) composite model. Finally, the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAFP) of vehicle exhaust sources and evaporative sources were analyzed using the maximum incremental reactivity (MIR) and fractional aerosol coefficient (FAC). The results showed that ρ(VOCs) in the tunnel was (2794.5±147.4) µg·m-3 during the experiment, among which halogenated hydrocarbons[(32.4±2.0)%] accounted for the highest proportion, followed by aromatic hydrocarbons[(27.5±0.6)%] and alkanes[(23.3±0.8)%]. Source apportionment of vehicular VOCs showed that exhaust emissions (62.5%)>evaporative emissions (37.5%), whereas the contribution of OFP was that exhaust emissions (71.9%)>evaporative emissions (28.1%), and the contribution of SOAFP was that exhaust emissions (75.8%)>evaporative emissions (24.2%). The dominant components of OFP in evaporative sources were m,p-diethylbenzene, isoprene, and trans-2-pentene, whereas m,p-diethylbenzene, m,p-xylene, and 1,2,3-trimethylbenzene were the dominant components of SOAFP. The major components of OFP in exhaust sources were m,p-xylene, 1,2,4-trimethylbenzene, and 1,3,5-trimethylbenzene, whereas m,p-xylene, m,p-diethylbenzene, and 1,3,5-trimethylbenzene were the dominant components of SOAFP. In regions where ethanol gasoline is used, special attention should be paid not only to the exhaust emissions control but also to strengthening the emissions reduction of VOCs from vehicle evaporative sources, especially the high active components such as aromatic hydrocarbons and alkenes.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental/métodos , Etanol , Gasolina/análise , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
7.
Front Biosci (Landmark Ed) ; 27(1): 23, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35090328

RESUMO

BACKGROUND: The expression levels of the programmed cell death ligand 1 (PD-L1), known as an immune-inhibitory molecule, are closely associated with cancer stem cell (CSCs) immune escape. Recently, PD-L1 has also been reported to be able to regulate the self-renewal of cancer stem cells. However, The expression and intrinsic role of PD-L1 in endometrial cancer stem-like cell (ECSC) maintenance and its underlying mechanism of action remain unclear. METHODS: Using flow cytometry and western blot assays, we have demonstrated that PD-L1 expression is higher in ECSCs derived from endometrial cancer than in nonstem-like cancer cells. Using mouse xenograft assays for ECSC tumorigenicity. Using gene reporter assay for uncovering the regulation mechanism of PD-L1 in the hypoxia. RESULTS: We revealed the high expression levels of PD-L1 in ECSCs and its correlation with self-renewal. We further found that PD-L1 knockdown reduced expression of several pluripotency-related genes (aldehyde dehydrogenase 1 (ALDH1), CD133, OCT4, SOX2, NANOG), impaired ECSC proliferation and undifferentiated colonies and decreased the number of CD133 positive ECSCs and the number of stem-like spheres. Furthermore, we found that PD-L1 knockdown inhibited ECSC tumorigenicity and the PD-L1 induced self-renewal capability of ECSCs was dependent upon hypoxia HIF-1α and HIF-2α activation. CONCLUSIONS: These data link ECSC maintenance to PD-L1 expression through hypoxia and suggest a promising target for PD1/PD-L1 immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias do Endométrio , Animais , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Feminino , Humanos , Hipóxia , Camundongos , Células-Tronco Neoplásicas/metabolismo
8.
Sci Signal ; 15(715): eabh2290, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982576

RESUMO

The kinase AKT (also known as protein kinase B) is a key regulator of cell proliferation, survival, and metabolism. In addition to being activated by growth factors, AKT is activated in response to DNA damage. Here, we found that the DNA damage response kinase DNA-PK sustains cell survival through a phosphorylation event that leads to increased AKT activity. In various cancer and noncancer cells in culture, DNA damage caused by ionizing radiation or topoisomerase inhibitors triggered DNA-PK­dependent phosphorylation of the mTOR complex 2 (mTORC2) subunit Sin1, which enabled its interaction with the guanine nucleotide exchange factor ECT2. Depleting Sin1 or ECT2 or disrupting the protein interaction or catalytic function of ECT2 attenuated DNA damage­induced AKT activation, thereby enhancing cellular sensitivity to DNA-damaging agents. Our findings elucidate a mechanism mediating DNA damage­induced AKT activation and cell survival.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Dano ao DNA , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
9.
Sci Total Environ ; 813: 152449, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-34942256

RESUMO

Zhengzhou, the provincial capital of Henan province in Central China and a major hub of the country's transportation network, has been suffering from severe summertime ozone (O3) pollution. Simultaneous field measurements of O3 and its precursors, including NOx, CO, HONO, and 106 volatile organic compounds (VOCs), were conducted at an urban site (the municipal environmental monitoring station, MEM) in Zhengzhou in July 2019. The Community Multiscale Air Quality (CMAQ) model, which incorporates the Master Chemical Mechanism (MCMv3.3.1), was modified to work as a 0-D observation-based photochemical box model to assess the sources and sinks of HOx radicals and O3, and the OH reactivity (KOH) and ozone formation potential (OFP) of major VOC groups. In addition, the O3-NOx-VOC sensitivity was evaluated using the relative incremental reactivity (RIR) and O3 formation isopleth techniques. The OH radicals were mainly generated from the propagation reaction of HO2 + NO (91-95%). The daily average mixing ratios of OH and HO2 radicals were significantly higher during high O3 days, reaching as high as 4.8 × 106 and 7.7 × 108 molecules cm-3, respectively. Photochemical O3 formation was mostly due to the conversion of NO to NO2 by HO2 radicals (52-54%), while the NO2 + OH reaction was the main contributor to O3 destruction (70- 76%). Alkenes and aromatics were the main anthropogenic VOC contributors to KOH and OFP. Contributions of biogenic VOCs became much more important on high O3 days, correlating with the increase in temperature and solar radiation. RIR analysis showed that the O3 formation was under the VOC-limited on low O3 days but was in the transition regime during the O3 pollution buildup and persisting days. These results are generally consistent with those based on the O3 formation isopleth. This paper provides important corroborative scientific evidence urgently needed by local governments to formulate O3 pollution control strategies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análise
10.
Environ Pollut ; 296: 118716, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34933059

RESUMO

The significant reduction in PM2.5 mass concentration after the outbreak of COVID-19 provided a unique opportunity further to study the formation mechanism of secondary inorganic aerosols. Hourly data of chemical components in PM2.5, gaseous pollutants, and meteorological data were obtained from January 1 to 23, 2020 (pre-lockdown) and January 24 to February 17, 2020 (COVID-lockdown) in Zhengzhou, China. Sulfate, nitrate, and ammonium were the main components of PM2.5 during both the pre-lockdown and COVID-lockdown periods. Compared with the pre-lockdown period, even though the concentration and proportion of nitrate decreased, nitrate was the dominant component in PM2.5 during the COVID-lockdown period. Moreover, nitrate production was enhanced by the elevated O3 concentration, which was favorable for the homogeneous and hydrolysis nitrate formation despite the drastic decrease of NO2. The proportion of sulfate during the COVID-lockdown period was higher than that before. Aqueous-phase reactions of H2O2 and transition metal (TMI) catalyzed oxidations were the major pathways for sulfate formation. During the COVID-lockdown period, TMI-catalyzed oxidation became the dominant pathway for aqueous-phase sulfate formation because the elevated acidity favored the dissolution of TMI. Therefore, the enhanced TMI-catalyzed oxidation affected by the elevated particle acidity dominated the sulfate formation, resulting in the slight increase of sulfate concentration during the COVID-lockdown period in Zhengzhou.


Assuntos
Poluentes Atmosféricos , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Peróxido de Hidrogênio , Pandemias , Material Particulado/análise , SARS-CoV-2 , Sulfatos
11.
Huan Jing Ke Xue ; 42(11): 5220-5227, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708961

RESUMO

In this study, a 2017-based emission inventory of ammonia(NH3) was established for Zhengzhou by using the emission factor method. The 1 km×1 km gridded emission inventory was mapped using GIS technology. The NH3 emissions between 2007 and 2017 and driving force between 1989 and 2017 were also analyzed. Results showed that the total 2017-based NH3 emission in Zhengzhou was 18143.3 t, and the average emission intensity reached 2.4 t·km-2. The top emission source was from agriculture, accounting for 63.4% of the total emission, followed by fugacity(11.3%). The main contribution sources of livestock were egg poultry, pigs, and cattle. Dengfeng, Xingyang, and Xinmi had the highest emissions, accounting for 19.3%, 16.5%, and 15.6% of the total emission, respectively. The NH3 emission was higher in the southern and central western regions of Zhengzhou and lower in the northeastern region. The NH3 emission in Zhengzhou showed a downward trend from 2007 to 2017. The NH3 emissions from 1987 to 2017 were similar to the environmental Kuznets Curve, i.e., the emissions increased first and then decreased with the increase of per capita gross domestic product(GDP) and urbanization rate.


Assuntos
Poluentes Atmosféricos , Agricultura , Poluentes Atmosféricos/análise , Amônia/análise , Animais , Bovinos , Cidades , Monitoramento Ambiental , Gado , Suínos
12.
Environ Pollut ; 288: 117982, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34426229

RESUMO

Ammonia (NH3) volatilization is one of the main pathways of nitrogen loss from cropland, resulting not only in economic losses, but also environmental and human health impacts. The magnitude and timing of NH3 emissions from cropland fertilizer application highly depends on agricultural practices, climate and soil factors, which previous studies have typically only considered at coarse spatio-temporal resolution. In this paper, we describe a first highly detailed empirical regression model for ammonia (ERMA) emissions based on 1443 field observations across China. This model is applied at county level by integrating data with unprecedented high spatio-temporal resolution of agricultural practices and climate and soil factors. Results showed that total NH3 emissions from cropland fertilizer application amount to 4.3 Tg NH3 yr-1 in 2017 with an overall NH3 emission factor of 12%. Agricultural production for vegetables, maize and rice are the three largest emitters. Compared to previous studies, more emission hotspots were found in South China and temporally, emission peaks are estimated to occur three months earlier in the year, while the total amount of emissions is estimated to be close to that calculated by previous studies. A second emission peak is identified in October, most likely related to the fertilization of the second crop in autumn. Incorporating these new findings on NH3 emission patterns will enable a better parametrization of models and hence improve the modelling of air quality and subsequent impacts on ecosystems through reactive N deposition.


Assuntos
Amônia , Ecossistema , Agricultura , Amônia/análise , China , Produtos Agrícolas , Fertilização , Fertilizantes/análise , Humanos , Nitrogênio/análise , Solo
13.
Huan Jing Ke Xue ; 42(8): 3663-3675, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309253

RESUMO

Based on the collected urban motor vehicle activity ownership and traffic flow of highways, combined with the mileage and source profiles of VOCs, using the emission factor method, we established high-resolution emission inventories from 2016 to 2019 for urban and 2016-based highway motor vehicles, respectively, in Henan Province, China. The results showed that gasoline vehicles, particularly minibuses and ordinary motorcycles, were the main contributors of CO, VOCs, and NH3, whereas heavy-duty and light-duty diesel trucks emitted SO2, NOx, and PM. Vehicles with China 1, China 3, and China 4 emission standards contributed significantly to pollutant emissions in the fleet. The temporal variation in traffic flow was consistent with the changes in freight and passenger traffic, with higher coefficients of variation for highways from August to October and the lowest in November. The weekly and daily changes in urban trunk roads showed distinct weekend effects and clear double-peak features, respectively. High-value emission areas were concentrated in urban centers with dense transport networks and high traffic volumes and on roads radiating outward from urban areas. The Lianhuo Expressway and the Beijing-Hong Kong-Macau Expressway were high-emission roads. Light-duty gasoline vehicles made the largest contribution to the ozone formation potential (OFP) of VOCs from motor vehicles. Five species, such as ethylene and propylene, contributed significantly to VOC emissions and OFP. The average annual growth rate of vehicle ownership from 2016 to 2019 was 5.7%. Compared with 2016, VOC emissions increased by 2.8% in 2019, whereas emissions of other pollutants showed decreasing trends of different degrees, with decreases of 76.3%, 51.7%, 50.3%, 43.1%, 16.7%, and 5.9% for SO2, PM2.5, PM10, NH3, CO, and NOx, respectively. The emission reduction percentage of each pollutant in 2019 under the control policies relative to the baseline scenario ranged from 15.6% to 82.4%.


Assuntos
Poluentes Atmosféricos , Emissões de Veículos , Poluentes Atmosféricos/análise , Pequim , China , Monitoramento Ambiental , Hong Kong , Macau , Veículos Automotores , Emissões de Veículos/análise
14.
Nat Commun ; 12(1): 3444, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103528

RESUMO

AKT is involved in a number of key cellular processes including cell proliferation, apoptosis and metabolism. Hyperactivation of AKT is associated with many pathological conditions, particularly cancers. Emerging evidence indicates that arginine methylation is involved in modulating AKT signaling pathway. However, whether and how arginine methylation directly regulates AKT kinase activity remain unknown. Here we report that protein arginine methyltransferase 5 (PRMT5), but not other PRMTs, promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at arginine 391 (R391). Mechanistically, AKT1-R391 methylation cooperates with phosphatidylinositol 3,4,5 trisphosphate (PIP3) to relieve the pleckstrin homology (PH)-in conformation, leading to AKT1 membrane translocation and subsequent activation by phosphoinositide-dependent kinase-1 (PDK1) and the mechanistic target of rapamycin complex 2 (mTORC2). As a result, deficiency in AKT1-R391 methylation significantly suppresses AKT1 kinase activity and tumorigenesis. Lastly, we show that PRMT5 inhibitor synergizes with AKT inhibitor or chemotherapeutic drugs to enhance cell death. Altogether, our study suggests that R391 methylation is an important step for AKT activation and its oncogenic function.


Assuntos
Arginina/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antineoplásicos/farmacologia , Biocatálise/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Metilação/efeitos dos fármacos , Camundongos Nus , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína-Arginina N-Metiltransferases/deficiência , Proteínas Proto-Oncogênicas c-akt/química , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Huan Jing Ke Xue ; 42(2): 604-615, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742854

RESUMO

Based on online monitoring data of air quality and meteorological parameters, the long-term variations, spatial differences, and meteorological influencing factors of ground-level ozone (O3) pollution in Zhengzhou were studied. In addition, the transport pathways and potential source regions of O3 were investigated. The results show that surface O3 concentrations at the city station in Zhengzhou City increased significantly during the period 2014-2018 (P<0.05) with a growth rate of 15.50 µg·(m3·a)-1, and the timespan of exceeding pollutant standards was extended. The monthly O3 variations showed an "M" pattern with the seasonal maximum in summer. The diurnal O3 variations showed a "single-peak" pattern with a diurnal concentrations peak at 15:00-16:00, while the diurnal peak at the rural station was relatively high (130.94 µg·m-3). At the urban station, the exceedance probability of O3 concentrations was relative high when hourly temperature (T) exceeded 23℃, relative humidity (RH) was less than 65%, wind speed (WS) ranged 2.0-4.0 m·s-1, and wind direction was southeast or northeast. Based on the multivariate linear fitting of impact factors on O3, the main controlling factors at the city and industrial sites were also identified as T and RH compared to T and WS at the traffic and suburb sites. Back trajectory analysis and potential sources of O3 during different seasons were significantly different, with the dominant transport trajectories during spring and summer being short-distance and slow-moving airflows from the south and northeast; autumn and winter were characterized by long-distance and quick-moving airflows from the northwest. The high O3 concentrations observed in summer were mainly affected by local photochemical formation and regional transport from Hebei, Shandong, and Anhui Provinces.

16.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670113

RESUMO

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.


Assuntos
Doenças Cardiovasculares/metabolismo , Doenças Metabólicas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Processamento de Proteína Pós-Traducional , Serina-Treonina Quinases TOR/metabolismo , Doenças Cardiovasculares/genética , Proliferação de Células , Humanos , Doenças Metabólicas/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Doenças Neurodegenerativas/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
17.
J Environ Sci (China) ; 99: 354-368, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33183714

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Peróxido de Hidrogênio , Ozônio/análise , Compostos Orgânicos Voláteis/análise
18.
J Environ Sci (China) ; 108: 44-57, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34465436

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Estações do Ano , Compostos Orgânicos Voláteis/análise
19.
Huan Jing Ke Xue ; 41(8): 3500-3510, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124322

RESUMO

In this study, volatile organic compound (VOC) species were measured at an urban site in Zhengzhou from January 3 to 23, 2019, to investigate the composition, variation characteristics, sources, and effects on secondary organic aerosol (SOA) formation of VOCs at different pollution levels. Results showed that oxygenated VOCs and alkanes were the main components of VOCs, while ethyl acetate and acetone were the most abundant species. During the process from clean days to heavy pollution days, the mixing ratio of VOCs approximately doubled, and the mixing ratios of most species continued to increase as the pollution level increased. Based on the positive matrix factorization (PMF) model, during the observation period, VOCs mainly originated from vehicle emissions, industrial emissions, combustion sources, solvent utilization, and liquefied petroleum gas (LPG) utilization. There were significant differences in the source contribution at different pollution levels, and the contributions of industrial emissions and solvent utilization during the heavy pollution days increased to 9 times and 3 times that of the clean days, respectively. With respect to the SOA formation potential (SOAp), aromatics were the component that contributed the most, and toluene and m/p-xylene were the species that contributed the most, while solvent utilization was the greatest source contributor. During the heavy pollution period, the total SOAp increased to approximately 2.6 times that of clean days. There is a great need to reduce winter haze pollution in Zhengzhou by strengthening the control of aromatic emissions and related sources such as solvent utilization.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Estações do Ano , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
20.
Huan Jing Ke Xue ; 41(10): 4436-4445, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124375

RESUMO

During the National Traditional Games of Ethnic Minorities (NTGEM) 2019, air quality in Zhengzhou was analyzed to evaluate the impact of pollution prevention and control measures on Zhengzhou. Ground-observed meteorological and pollutant data as well as the chemical compositions of volatile organic compounds (VOCs) were investigated. The results showed that the six parameters of pollutants in the safeguard period in 2019 indicated a downward trend as compared with that during the same time in 2018, and the average concentrations of PM2.5 and PM10 were decreased by 16.2% and 25.1%, respectively. However, the average concentration of O3 was only reduced by 3.7%. The daily proportions of primary pollutants of O3 increased to 90% during the NTGEM, and the ozone pollution was severe in this period. Meanwhile, the concentration of total volatile organic compounds (TVOCs) in the safeguard period was 26.21×10-9, which was significantly lower than that during the historical period. Six emission sources of the VOCs were identified using PMF model, including vehicle exhaust (28%), LPG evaporation (21%), combustion source (16%), industrial emissions (15%), solvent utilization (15%), and biogenic VOCs (5%). During the NTGEM period, the control of combustion sources and industrial sources was evident.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
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