Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 71
Filtrar
2.
Environ Res ; 211: 113093, 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35292245

RESUMO

Hydroxymethanesulfonate (HMS), a key marker species of aqueous-phase processing, plays a significant role in sulfur budget in atmosphere. Here we have a comprehensive characterization of HMS at urban and rural sites in North China Plain (NCP) by using the real-time measurements from a high-resolution aerosol mass spectrometer (AMS) and a single-particle AMS together with offline filter analysis. Our results showed much higher winter concentration of HMS at the rural site (average±1σ: 2.58 ± 2.56 µg m-3) than that (1.70 ± 2.68 µg m-3) in Beijing due to the more frequent fog events, low particle acidity and high concentration of precursors. The HMS on average contributed 6.3% and 5.2% to organic aerosol (OA), and 16% and 12% to the total particulate sulfur, at the rural and urban sites, respectively. HMS was highly correlated with aqueous-phase secondary OA and sulfate, and its contribution to the total particulate sulfur increased significantly as a function of relative humidity demonstrating the effective HMS production from aqueous-phase processing. Single-particle analysis showed that HMS-containing particles were mainly mixed with amine-related compounds. In addition, we found that organosulfur compounds (OS) estimated from sulfur-containing fragments of AMS correlated well with HMS at both urban and rural sites. While OS at the rural site was dominated by HMS, other types of OS were also important in urban area. The high HMS also affected the estimation of particle acidity using the AMS measured and predicted ammonium, particularly during severe haze episodes. Overall, our results demonstrated the importance of HMS in winter in NCP, and it could be more important in total particulate sulfur budget as the continuous decrease in sulfate in the future.

3.
Sci Total Environ ; 829: 154661, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35314216

RESUMO

The Fenwei Plain (FWP) continues to be one of the most polluted regions in China despite the improvement of air quality in recent years. However, our understanding of aerosol optical properties (AOP) and its relationship with aerosol composition particularly in cold season is far from complete. Here we conducted three-month measurements of AOP from November 2020 to January 2021 in the FWP along with fine particle composition and water-soluble organic aerosol (WSOA) measurements. Our results showed rapid transitions in AOP from November to January due to the enhanced primary emissions and the decreased aqueous-phase processing. The single scattering albedo (SSA) decreased from 0.85 to 0.78, while the absorption ÅngstrÓ§m exponent (AAE) increased from 1.41 to 1.60, demonstrating the increasing role of absorbing aerosol and brown carbon in cold season. Further analysis showed that SSA increased significantly with the fraction of secondary inorganic aerosol, while AAE was highly correlated with the fraction of primary OA (POA), highlighting the different impacts of primary and secondary aerosol on AOP. Chemical apportionment showed the dominant contributions of ammonium nitrate (29%) and ammonium sulfate (27%) to particle extinction before heating season, while that of POA increased to 27% during heating season. Although the pollution level showed a clear increase during the heating season, the changes in visibility were small due to the decreased mass extinction efficiency from 3.48 to 2.91 m2 g-1. Positive matrix factorization illustrated a clear transition in WSOA composition from the dominance of secondary OA (SOA) in November to POA in heating season. Compared with the large decrease in water-soluble aqueous-phase SOA, the consistently high concentration of photochemical-related SOA elucidated the presence of strong photochemical processing in cold season. Overall, our results demonstrate the significant transition in primary emissions and secondary formation in cold season, and such changes have affected AOP substantially.

4.
Drug Deliv ; 29(1): 506-518, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35147065

RESUMO

The field of biomedical research has recently been interested in nanoplatforms with various functionalities, such as cancer drug carriers and MRI and optical imaging, as well as thermal treatment, among other things. As a result of the present investigation, a unique multifunctional liposome (MFL) was established in this investigation. Using radiofrequency-induced imaging and drug release based on magnetic field impact, a dual drug delivery targeted with tumor multi-mechanism treatment was made more effective. The C60 (fullerene) surface was coated with iron nanocomposites to establish the proposed nanosystems, and PEGylation was used (Fe3O4-C60-PEG2000). For fullerene radiofrequency-triggered drug release, thermosensitive DPPC liposomes with folate-DSPE-PEG2000 enveloped the binary nanosystems and doxorubicin (DOX). The in vitro cytotoxicity of the nanocomposites was confirmed by the liver metastasis in HT-29 colon cancer cells using radiofrequency. The flow cytometry analysis confirmed the apoptosis cell death mechanism. The thermal treatment combined chemotherapeutic MFL nano framework transformed radiofrequency radiation from thermoresponsive liposomes, which was noticed both in vivo and in vitro. Due to their superior active tumor targeting and magnetic targeting characteristics, the MFL could also selectively destroy cancerous liver cells in highly co-localized targets.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Lipossomos/química , Neoplasias Hepáticas/patologia , Ablação por Radiofrequência/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Química Farmacêutica , Neoplasias do Colo/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fulerenos/química , Neoplasias Hepáticas/secundário , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Tamanho da Partícula , Polietilenoglicóis/química , Propriedades de Superfície , Carga Tumoral/efeitos dos fármacos
5.
Food Res Int ; 152: 110901, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35181077

RESUMO

Aspergillus cristatus is the dominant fungus involved in the fermentation of Fuzhuan brick tea (FBT). The intracellular polysaccharides (IPSs) from A. cristatus (MK346334, NCBI), isolated from FBT, exhibited immunomodulatory activity in vitro while the effects in vivo on immune system and gut microbiota remain unclear. In this study, IPSs and the purified fraction (IPSs-2) from IPSs were prepared and their immunomodulatory activities were investigated with cyclophosphamide (Cy)-induced immunosuppressive mice. As results, IPSs strengthened the immune function, manifesting in the improvement of body weight, daily intake, immune organ indices, cytokines and immunoglobulin. Meanwhile, IPSs attenuated Cy-induced intestinal barrier injury and promoted the expression of tight junction proteins and mucin, reinforcing the intestinal barrier function. Moreover, IPSs not only promoted the production of short-chain fatty acids and the expression of G protein-coupled receptor (GPR), but also balanced dysbiosis of gut microbiota through elevating the growth of beneficial bacteria while reducing pathobionts to maintain the homeostasis of the microbial ecology. These results suggested that IPSs exerted immunomodulatory activity linking with the restoration of intestinal barrier function and regulation of gut microbiota, which contributes to the development of novel probiotics and effective immunomodulators for strengthening host immunity and gut health.


Assuntos
Microbioma Gastrointestinal , Animais , Aspergillus , Imunidade , Camundongos , Micélio/metabolismo , Polissacarídeos/farmacologia , Chá/metabolismo
6.
Environ Res ; 209: 112751, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35077717

RESUMO

Secondary organic aerosols (SOA) constitute a large fraction of atmospheric aerosols, yet our knowledge of the formation and aging processes of SOA in megacities of China is still limited. In this work, the formation and aging processes of SOA in winter in Beijing was investigated using a high-resolution aerosol mass spectrometer (AMS) and an oxidation flow reactor (OFR). Our results showed that the OA enhancement from OH aging peaked at ∼3.9 equivalent days with an average enhancement of 0.9 (±0.3) µg m-3. Positive matrix factorization analysis of AMS-OFR data identified three primary OA (POA) and two SOA factors. While the concentrations of POA factors decreased as a function of photochemical age, the two SOA factors showed clear enhancements by 2.5 and 4.3 µg m-3 at ∼3.9 and ∼2.6 days of equivalent photochemical age, respectively. The average contribution of SOA to the total OA was 47% in ambient air and 87% in OFR-oxidized ambient air. The elevated oxygen-to-carbon (O/C) ratio from 0.49 to 0.77-0.82 and the decreased hydrogen-to-carbon (H/C) from 1.37 to ∼1.1 highlighted the formation of more oxidized SOA during photochemical aging in winter in Beijing. The ubiquitous SOA enhancement as a function of OA levels indicated the significant formation potential of SOA in winter, and it varied differently among different episodes. In particular, we observed a maximum SOA enhancement of 38.6 µg m-3 during a biomass burning event. This result demonstrates that photochemical oxidation of ubiquitous biomass burning emissions can be a large source of SOA in winter in North China Plain.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Pequim , China
7.
Cell Death Differ ; 29(5): 988-1003, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35034103

RESUMO

Recent evidence suggests that small nucleolar RNAs (snoRNAs) are involved in the progression of various cancers, but their precise roles in hepatocellular carcinoma (HCC) remain largely unclear. Here, we report that SNORD17 promotes the progression of HCC through a positive feedback loop with p53. HCC-related microarray datasets from the Gene Expression Omnibus (GEO) database and clinical HCC samples were used to identify clinically relevant snoRNAs in HCC. SNORD17 was found upregulated in HCC tissues compared with normal liver tissues, and the higher expression of SNORD17 predicted poor outcomes in patients with HCC, especially in those with wild-type p53. SNORD17 promoted the growth and tumorigenicity of HCC cells in vitro and in vivo by inhibiting p53-mediated cell cycle arrest and apoptosis. Mechanistically, SNORD17 anchored nucleophosmin 1 (NPM1) and MYB binding protein 1a (MYBBP1A) in the nucleolus by binding them simultaneously. Loss of SNORD17 promoted the translocation of NPM1 and MYBBP1A into the nucleoplasm, leading to NPM1/MDM2-mediated stability and MYBBP1A/p300-mediated activation of p53. Interestingly, p300-mediated acetylation of p53 inhibited SNORD17 expression by binding to the promoter of SNORD17 in turn, forming a positive feedback loop between SNORD17 and p53. Administration of SNORD17 antisense oligonucleotides (ASOs) significantly suppressed the growth of xenograft tumors in mice. In summary, this study suggests that SNORD17 drives cancer progression by constitutively inhibiting p53 signaling in HCC and may represent a potential therapeutic target for HCC.

8.
Br J Nutr ; : 1-14, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35057874

RESUMO

Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 µg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 µg/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 µg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.

9.
Sci Total Environ ; 802: 149695, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438127

RESUMO

Particle number size distribution (PNSD) is of importance for understanding the mechanisms of particle growth, haze formation and climate impacts. However, the measurements of PNSD aloft in megacities are very limited. Here we report the first simultaneous winter measurements of size-resolved particle number concentrations along with collocated gaseous species and aerosol composition at ground level and 260 m in Beijing. Our study showed that the vertical differences of particle number concentrations between ground level and aloft varied significantly as a function of particle size throughout the study. Further analysis illustrated the impacts of boundary dynamics and meteorological conditions on the vertical differences of PNSD. In particular, the temperature and relative humidity inversions were one of the most important factors by decoupling the boundary layer into different sources and processes. Positive matrix factorization analysis identified six sources of PNSD at both ground level and city aloft. The local source emissions dominantly contributed to Aitken-mode particles, and showed the largest vertical gradients in the city. Comparatively, the regional particles were highly correlated between ground level and city aloft, and the vertical differences were relatively stable throughout the day. Our results point towards a complex vertical evolution of PNSD due to the changes in boundary layer dynamics, meteorological conditions, sources, and processes in megacities.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Pequim , China , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Estações do Ano
10.
Crit Rev Food Sci Nutr ; : 1-18, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34964426

RESUMO

Fuzhuan brick tea (FBT) is a traditional popular beverage in the border regions of China. Nowadays, FBT has been attracted great attention due to its uniquely flavor and various health-promoting functions. An increasing number of efforts have been devoted to the studies on health benefits and chemistry of FBT over the last decades. However, FBT was still received much less attention than green tea, oolong tea and black tea. Therefore, it is necessary to review the current encouraging findings about processing, microorganisms, chemical constituents, health benefits and potential risk of FBT. The fungus fermentation is the key stage for processing of FBT, which is involved in a complex and unique microbial fermentation process. The fungal community in FBT is mainly dominated by "golden flower" fungi, which is identified as Aspergillus cristatus. A great diversity of novel compounds is formed and identified after a series of biochemical reactions during the fermentation process of FBT. FBT shows various biological activities, such as antioxidant, anti-inflammatory, anti-obesity, anti-bacterial, and anti-tumor activities. Furthermore, the potential risk of FBT was also discussed. It is expected that this review could be useful for stimulating further research of FBT.

11.
Nat Commun ; 12(1): 6692, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795255

RESUMO

Metastatic cancer is associated with poor patient prognosis but its spatiotemporal behavior remains unpredictable at early stage. Here we develop MetaNet, a computational framework that integrates clinical and sequencing data from 32,176 primary and metastatic cancer cases, to assess metastatic risks of primary tumors. MetaNet achieves high accuracy in distinguishing the metastasis from the primary in breast and prostate cancers. From the prediction, we identify Metastasis-Featuring Primary (MFP) tumors, a subset of primary tumors with genomic features enriched in metastasis and demonstrate their higher metastatic risk and shorter disease-free survival. In addition, we identify genomic alterations associated with organ-specific metastases and employ them to stratify patients into various risk groups with propensities toward different metastatic organs. This organotropic stratification method achieves better prognostic value than the standard histological grading system in prostate cancer, especially in the identification of Bone-MFP and Liver-MFP subtypes, with potential in informing organ-specific examinations in follow-ups.


Assuntos
Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Genômica/métodos , Aprendizado de Máquina , Neoplasias/genética , Progressão da Doença , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estimativa de Kaplan-Meier , Mutação , Metástase Neoplásica , Neoplasias/patologia , Especificidade de Órgãos/genética , Prognóstico , Fatores de Risco
12.
Neural Netw ; 143: 327-344, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34182234

RESUMO

Credit risk evaluation is a crucial yet challenging problem in financial analysis. It can not only help institutions reduce risk and ensure profitability, but also improve consumers' fair practices. The data-driven algorithms such as artificial intelligence techniques regard the evaluation as a classification problem and aim to classify transactions as default or non-default. Since non-default samples greatly outnumber default samples, it is a typical imbalanced learning problem and each class or each sample needs special treatment. Numerous data-level, algorithm-level and hybrid methods are presented, and cost-sensitive support vector machines (CSSVMs) are representative algorithm-level methods. Based on the minimization of symmetric and unbounded loss functions, CSSVMs impose higher penalties on the misclassification costs of minority instances using domain specific parameters. However, such loss functions as error measurement cannot have an obvious cost-sensitive generalization. In this paper, we propose a robust cost-sensitive kernel method with Blinex loss (CSKB), which can be applied in credit risk evaluation. By inheriting the elegant merits of Blinex loss function, i.e., asymmetry and boundedness, CSKB not only flexibly controls distinct costs for both classes, but also enjoys noise robustness. As a data-driven decision-making paradigm of credit risk evaluation, CSKB can achieve the "win-win" situation for both the financial institutions and consumers. We solve linear and nonlinear CSKB by Nesterov accelerated gradient algorithm and Pegasos algorithm respectively. Moreover, the generalization capability of CSKB is theoretically analyzed. Comprehensive experiments on synthetic, UCI and credit risk evaluation datasets demonstrate that CSKB compares more favorably than other benchmark methods in terms of various measures.


Assuntos
Inteligência Artificial , Máquina de Vetores de Suporte , Algoritmos
13.
Aging (Albany NY) ; 13(9): 13300-13317, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891563

RESUMO

Liver cancer is the sixth most common malignancy and the fourth leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) is the primary type of liver cancer. Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SnoRD126 is an orphan C/D box snoRNA. How snoRD126 activates the PI3K-AKT pathway, and which domain of snoRD126 exerts its oncogenic function was heretofore completely unknown. Here, we demonstrate that snoRD126 binds to hnRNPK protein to regulate FGFR2 expression and activate the PI3K-AKT pathway. Importantly, we identified the critical domain of snoRD126 responsible for its cancer-promoting functions. Our study further confirms the role of snoRD126 in the progression of HCC and suggests that knockdown snoRD126 may be of potential value as a novel therapeutic approach for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Adulto , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Nucleolar Pequeno/genética
14.
Indoor Air ; 31(5): 1364-1376, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33876836

RESUMO

Most of human exposure to atmospheric pollutants occurs indoors, and the components of outdoor aerosols may have been changed in the way before reaching indoor spaces. Here we conducted real-time online measurements of mass concentrations and chemical composition of black carbon and the non-refractory species in PM2.5 in an occupied office for approximately one month. The open-close windows and controlled dampness experiments were also performed. Our results show that indoor aerosol species primarily originate from outdoors with indoor/outdoor ratio of these species typically less than unity except for certain organic aerosol (OA) factors. All aerosol species went through filtration upon transport indoors. Ammonium nitrate and fossil fuel OA underwent evaporation or particle-to-gas partitioning, while less oxidized secondary OA (SOA) underwent secondary formation and cooking OA might have indoor sources. With higher particulate matter (PM) mass concentration outdoors than in the office, elevated natural ventilation increased PM exposure indoors and this increased exposure was prolonged when outdoor PM was scavenged. We found that increasing humidity in the office led to higher indoor PM mass concentration particularly more oxidized SOA. Overall, our results highlight that indoor exposure of occupants is substantially different from outdoor in terms of mass concentrations and chemical species.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Monitoramento Ambiental , Culinária , Humanos , Umidade , Tamanho da Partícula , Material Particulado , Ventilação
15.
Sci Total Environ ; 770: 144821, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33736402

RESUMO

The light absorption black carbon (BC) and brown carbon (BrC) are two important sources of uncertainties in radiative forcing estimate. Here we investigated the light absorption enhancement (Eabs) of BC due to coated materials at an urban (Beijing) and a rural site (Gucheng) in North China Plain (NCP) in winter 2019 by using a photoacoustic extinctiometer coupled with a thermodenuder. Our results showed that the average (±1σ) Eabs was 1.32 (±0.15) at the rural site, which was slightly higher than that at the urban site (1.24 ± 0.15). The dependence of Eabs on coating materials was found to be relatively limited at both sites. However, Eabs presented considerable increases as a function of relative humidity below 70%. Further analysis showed that Eabs during non-heating period in Beijing was mainly caused by secondary components, while it was dominantly contributed by enhanced primary emissions in heating season at both sites. In particular, aerosol particles mixed with coal combustion emissions had a large impact on Eabs (>1.40), while the fresh traffic emissions and freshly oxidized secondary OA (SOA) had limited Eabs (1.00-1.23). Although highly aged or aqueous-phase processed SOA coated on BC showed the largest Eabs, their contributions to the bulk absorption enhancement were generally small. We also quantified the absorption of BrC and source contributions. The results showed the BrC absorption at the rural site was nearly twice that of urban site, yet absorption Ångström exponents were similar. Multiple linear regression analysis highlighted the major sources of BrC being coal combustion emissions and photochemical SOA at both sites with additional biomass burning at the rural site. Overall, our results demonstrated the relatively limited winter light absorption enhancement of BC in different chemical environments in NCP, which needs be considered in regional climate models to improve BC radiative forcing estimates.

16.
Oncogene ; 40(16): 2898-2909, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33742127

RESUMO

Molecular-based classifications of gastric cancer (GC) were recently proposed, but few of them robustly predict clinical outcomes. While mutation and expression signature of protein-coding genes were used in previous molecular subtyping methods, the noncoding genome in GC remains largely unexplored. Here, we developed the fast long-noncoding RNA analysis (FLORA) method to study RNA sequencing data of GC cases, and prioritized tumor-specific long-noncoding RNAs (lncRNAs) by integrating clinical and multi-omic data. We uncovered 1235 tumor-specific lncRNAs, based on which three subtypes were identified. The lncRNA-based subtype 3 (L3) represented a subgroup of intestinal GC with worse survival, characterized by prevalent TP53 mutations, chromatin instability, hypomethylation, and over-expression of oncogenic lncRNAs. In contrast, the lncRNA-based subtype 1 (L1) has the best survival outcome, while LINC01614 expression further segregated a subgroup of L1 cases with worse survival and increased chance of developing distal metastasis. We demonstrated that LINC01614 over-expression is an independent prognostic factor in L1 and network-based functional prediction implicated its relevance to cell migration. Over-expression and CRISPR-Cas9-guided knockout experiments further validated the functions of LINC01614 in promoting GC cell growth and migration. Altogether, we proposed a lncRNA-based molecular subtype of GC that robustly predicts patient survival and validated LINC01614 as an oncogenic lncRNA that promotes GC proliferation and migration.


Assuntos
Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica/métodos , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Humanos , Oncogenes , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
17.
Biomed Pharmacother ; 137: 111295, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550042

RESUMO

During the past decades, tryptophan metabolism disorder was discovered to play a vital and complex role in the development of cancer. Indoleamine 2,3-dioxygenase 2 (IDO2) is one of the initial and rate-limiting enzymes of the kynurenine pathway of tryptophan catabolism. Increasing evidence indicates that IDO2 is upregulated in some tumors and plays a role in the development of cancer. In spite of the growing body of research, few reviews focused on the role of IDO2 in cancer. Here, we review the emerging knowledge on the roles of IDO2 in cancer and its potential as a therapeutic target. Firstly, the main biological features and regulatory mechanisms are reviewed, after which we focus on the expression and roles of IDO2 in cancer. Finally, we discuss the potential of IDO2 as a therapeutic target for cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Animais , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Terapia de Alvo Molecular , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Transdução de Sinais
18.
Faraday Discuss ; 226: 173-190, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411881

RESUMO

Haze episodes, characterised by extremely high aerosol concentrations and a reduction in visibility to less than 10 km, are a frequent occurrence in wintertime Beijing, despite policy interventions leading to an overall improvement in average annual air quality. The main drivers in the onset of haze episodes in wintertime Beijing are changing synoptic conditions, however, aerosol-radiation interactions and their feedback on boundary layer meteorology are thought to play an essential role in the intensity and longevity of haze episodes. In this study we use a coupled LES aerosol-radiation model (UCLALES-SALSA), which we have recently configured for the urban environment of Beijing. The model's high resolution and control over meteorological and aerosol conditions as well as atmospheric processes means we can directly elucidate and quantify the importance of specific aspects of the aerosol-radiation-meteorology feedback in the cumulative stage of Beijing haze. The main results presented here show (a) synoptic scale meteorology has a larger impact on boundary layer suppression than high aerosol concentrations and (b) unlike previous results obtained using regional models or observationally driven analyses, there is no threshold value at which the aerosol-radiation-meteorology feedback has a significant effect on PBL height. Rather, our work shows that for the aerosol composition in this case study, the role of the feedback effect in reducing PBL height increases under shallow boundary layer conditions and with increasing pollution loading in an almost linear fashion. This lack of a threshold found for our case study has important policy implications since interventions based on such a value will not result in large reductions associated with turning off the feedback process. Furthermore, this work directly shows that although the right synoptic changes are a prerequisite for pollution episodes in Beijing, local and regional emissions drive increases in aerosol load that are sufficient to initiate the aerosol feedback loop. This further drives suppression of the boundary layer top and promotes stagnation of air and increased stability, which can be self-sustaining. This results in higher surface aerosol concentrations for extended periods of time, with severe consequences for human health [Lv et al., Atmos. Environ., 2016, 124, 98-108; Wang et al., Atmos. Chem. Phys., 2019, 19(10), 6949-6967].

19.
Environ Sci Technol ; 55(2): 842-853, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33410677

RESUMO

The formation of isoprene nitrates (IsN) can lead to significant secondary organic aerosol (SOA) production and they can act as reservoirs of atmospheric nitrogen oxides. In this work, we estimate the rate of production of IsN from the reactions of isoprene with OH and NO3 radicals during the summertime in Beijing. While OH dominates the loss of isoprene during the day, NO3 plays an increasingly important role in the production of IsN from the early afternoon onwards. Unusually low NO concentrations during the afternoon resulted in NO3 mixing ratios of ca. 2 pptv at approximately 15:00, which we estimate to account for around a third of the total IsN production in the gas phase. Heterogeneous uptake of IsN produces nitrooxyorganosulfates (NOS). Two mono-nitrated NOS were correlated with particulate sulfate concentrations and appear to be formed from sequential NO3 and OH oxidation. Di- and tri-nitrated isoprene-related NOS, formed from multiple NO3 oxidation steps, peaked during the night. This work highlights that NO3 chemistry can play a key role in driving biogenic-anthropogenic interactive chemistry in Beijing with respect to the formation of IsN during both the day and night.


Assuntos
Hemiterpenos , Nitratos , Aerossóis/análise , Pequim , Butadienos/análise , Hemiterpenos/análise , Nitratos/análise
20.
Am J Surg ; 222(2): 383-389, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33388133

RESUMO

BACKGROUND: The definition and prognostic value of a wide resection margin remains controversial. The aim of this study was to assess the relevance of resection margin length for survival following intrahepatic cholangiocarcinoma (ICC) resection. METHODS: Patients scheduled for curative resection for ICC between 2015 and 2018 were identified from an institutional database. Demographic data, pathological margin length, and oncologic outcomes were collected and analyzed. RESULTS: This study included 126 patients, of whom 78% underwent anatomical hepatectomy. The resection margin was <0.5, <1.0, and <1.5 cm in 73 (60%), 92 (73%), and 109 (87%) patients, respectively. A resection margin ≥1.0 cm was associated with favorable overall survival (OS) (HR: 0.403; 95% CI: 0.191-0.854; P = 0.018) and recurrence-free survival (RFS) (HR: 0.436; 95% CI: 0.232-0.817; P = 0.010). In the anatomical hepatectomy group, a resection margin ≥1.0 cm was an independent predictor of superior OS (HR: 0.451; 95% CI: 0.208-0.977; P = 0.043) and RFS (HR: 0.470; 95% CI: 0.242-0.914; P = 0.026). CONCLUSIONS: A resection margin ≥1.0 cm was associated with significantly improved survival in ICC. Therefore, a clear margin of at least 1.0 cm should be achieved during ICC resection.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Margens de Excisão , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...