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Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m3 and from 200 to 20,347 pg/m3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m3, GDPC: 13.9-465 pg/m3). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m3. Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry.
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Monitoramento Ambiental , Ésteres , Organofosfatos , China , Ésteres/análise , Medição de Risco , Organofosfatos/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Retardadores de Chama/análiseRESUMO
Endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in mammalian cells. The physical connection between them is mitochondria associated ER membranes (MAM). In recent years, studies on endoplasmic reticulum and mitochondria have shifted from independent division to association and comparison, especially MAM has gradually become a research hotspot. MAM connects the two organelles, not only to maintain their independent structure and function, but also to promote metabolism and signal transduction between them. This paper reviews the morphological structure and protein localization of MAM, and briefly analyzes the functions of MAM in regulating Ca2+ transport, lipid synthesis, mitochondrial fusion and fission, endoplasmic reticulum stress and oxidative stress, autophagy and inflammation. Since ER stress and mitochondrial dysfunction are important pathological events in neurological diseases including ischemic stroke, MAM is likely to play an important role in cerebral ischemia by regulating the signaling of the two organelles and the crosstalk of the two pathological events.
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Isquemia Encefálica , Membranas Mitocondriais , Animais , Humanos , Membranas Mitocondriais/metabolismo , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Transdução de Sinais , MamíferosRESUMO
Leukemia inhibitory factor (LIF) is an important growth factor that supports the culture and maintenance of spermatogonial stem cells (SSCs) by suppressing spontaneous differentiation. Different LIF sequences may lead to differences in function. The protein sequences of buffalo LIF and mouse LIF differed by 65.5% according to MEGA software analysis. The PB-LIF-GFP-Puro vector was constructed, and the CHO-K1 cell line was established. The final LIF protein concentration in the CHO-K1 cell culture medium was approximately 4.268 ng/mL. Here, we report that buffalo LIF effectively maintains the self-renewal of buffalo spermatogonia during culture. Buffalo spermatogonia were cultured in conditioned medium containing no LIF (0 ng/mL), mouse LIF (1 ng/mL), mouse LIF (10 ng/mL), or buffalo LIF (1 ng/mL). Furthermore, the effects of mouse LIF and buffalo LIF culture on the maintenance of buffalo spermatogonia were determined by analyzing cell colony formation, quantitative real-time polymerase chain reaction, cell immunofluorescence, and cell counting. The buffalo LIF (1 ng/mL) group showed similar maintenance of the proliferation of buffalo spermatogonia to that in the mouse LIF (10 ng/mL) group. These results demonstrated that the proliferation of buffalo spermatogonia can be maintained in vitro by adding a low dose of buffalo LIF. This study provides a foundation for the further optimization of in vitro buffalo SSC culture systems.
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Espermatogônias , Células-Tronco , Animais , Masculino , Camundongos , Fator Inibidor de Leucemia/metabolismo , Fator Inibidor de Leucemia/farmacologia , Meios de Cultura , Diferenciação Celular , Células CultivadasRESUMO
Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.
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Vírus da Influenza A Subtipo H1N1 , Interferon Tipo I , Infecções por Orthomyxoviridae , Camundongos , Animais , Capsaicina/farmacologia , Fator de Transcrição STAT3 , Transdução de Sinais , Proteínas de Transporte , Replicação ViralRESUMO
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. METHODS: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. RESULTS: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. CONCLUSIONS: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Tiossemicarbazonas , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Simulação de Acoplamento Molecular , Transdução de Sinais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Human exposure to dichlorodiphenyltrichloroethanes (DDTs) and the subsequent risk to human health remain an important concern due to the "new" input of DDTs in the environment, especially since exposure to DDTs in indoor microenvironments is often ignored. In this study, we identified a new source of DDT emission in indoor environments and evaluated the health risk from the exposure to DDTs by investigating DDTs in indoor and outdoor dust, air, and coatings of household items in rural areas of Qingyuan, South China. The concentrations of DDTs in house dust and air were < MQL (method quantification limit)-3450 ng/g (median 42.4 ng/g) and 22.7-965 pg/m3 (median 49.5 pg/m3), respectively, which were significantly higher than the outdoor DDT values. Dichlorodiphenyldichloroethylene (DDE) was the main isomer in air samples, while DDT was the dominant isomer in indoor dust. Significant correlations between different DDT isomers were observed in indoor samples but not in outdoor samples. Furniture coating was identified as a source of DDTs in the indoor dust. The total daily exposure dose of DDTs (1.75 × 10-2 ng/kg bw/day for adults and 1.28 × 10-1 ng/kg bw/day for toddlers) through inhalation, dust ingestion, and dermal contact was found unlikely to pose a health risk. Our findings provide new insights into the emission sources and health risks caused by DDT indoors, highlighting the need to further investigate the toxicity mechanisms of parent DDT compound.
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Poluição do Ar em Ambientes Fechados , DDT , Adulto , Humanos , DDT/análise , Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , China , Diclorodifenil Dicloroetileno , Monitoramento Ambiental/métodosRESUMO
Background: Ischemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD+) and butylphthalide (NBP) on in vitro and in vivo ischemic stroke models. Methods: Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cerebral infarct volume, neurobehavioral indices, antioxidant activity, ATP level and lactic acid content were determined. The neuroprotective effects of NAD+ or NBP were compared using sirtuin inhibitor niacinamide (NAM). Results: Intraperitoneal injection of NBP within 4 h or intravenous injection of NAD+ within 1 h after t-MCAO/R significantly reduced the volume of infarcts, cerebral edema, and neurological deficits. Administration of NAD+ and NBP immediately after t-MCAO/R in mice showed similar neuroprotection against acute and long-term ischemic injury. Both NAD+ and NBP significantly inhibited the accumulation of MDA and H2O2 and reduced oxidative stress. NAD+ was superior to NBP in inhibiting lipid oxidation and DNA damage. Furthermore, although both NAD+ and NBP improved the morphology of mitochondrial damage induced by ischemia/reperfusion, NAD+ more effectively reversed the decrease of ATP and increase of lactic acid after ischemia/reperfusion compared with NBP. NAD+ but not NBP treatment significantly upregulated SIRT3 in the brain, but the sirtuin inhibitor NAM could abolish the protective effect of NAD+ and NBP by inhibiting SIRT1 or SIRT3. Conclusions: These results confirmed the protective effects of NAD+ and NBP on cerebral ischemic injury. NBP and NAD+ showed similar antioxidant effects, while NAD+ had better ability in restoring energy metabolism, possibly through upregulating the activity of SIRT1 and SIRT3. The protection provided by NBP against cerebral ischemia/reperfusion may be achieved through SIRT1.
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[This corrects the article DOI: 10.3389/fped.2022.714054.].
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Very early onset inflammatory bowel disease (VEO-IBD) is characterized by multifactorial chronic recurrent intestinal inflammation. Compared with elderly patients, those with VEO-IBD have a more serious condition, not responsive to conventional treatments, with a poor prognosis. Recent studies found that genetic and immunologic abnormalities are closely related to VEO-IBD. Intestinal immune homeostasis monogenic defects (IIHMDs) are changed through various mechanisms. Recent studies have also revealed that abnormalities in genes and immune molecular mechanisms are closely related to VEO-IBD. IIHMDs change through various mechanisms. Epigenetic factors can mediate the interaction between the environment and genome, and genetic factors and immune molecules may be involved in the pathogenesis of the environment and gut microbiota. These discoveries will provide new directions and ideas for the treatment of VEO-IBD.
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INTRODUCTION: Ankyloglossia is a situation where the tongue tip cannot go beyond the mandibular incisor because the frenulum linguae is short. It could affect children's health by interfering with their ability to talk, breast feeding and dental development. The most effective measure to control ankyloglossia is the surgical method. However, which surgical procedure is the best one is still controversial. Thus, this protocol aims to assess the effectiveness of different surgical interventions in children with ankyloglossia. METHODS AND ANALYSIS: PubMed, EMBASE, Cochrane Library, Web of Science and OVID will be searched for relevant information from inception to 31 May 2022. Observational studies in English that investigate the association between surgical methods and ankyloglossia will be included in this protocol. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Quality Assessment Scale for longitudinal studies will be used to assess the included studies. The improvement of breast feeding and nipple pain will be the primary outcome. STATA V.15.1 will do the statistical analysis in the meta-analysis. Subgroup and meta-regression will be carried out based on the characteristics of included studies. ETHICS AND DISSEMINATION: This systematic review and meta-analysis will summarise relevant information on the effects of different surgical treatments on patients with ankyloglossia. The results will be disseminated through peer-reviewed publications. The data included in this study will be extracted from the published original studies. Thus, ethical approval and informed consent will not be required. PROSPERO REGISTRATION NUMBER: CRD42022323350.
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Anquiloglossia , Feminino , Criança , Humanos , Anquiloglossia/cirurgia , Estudos Transversais , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Aleitamento Materno , Projetos de PesquisaRESUMO
Four new staphylinid species from China are described, based on material collected from Tangli Mountain, Yunnan: Euconnus (s. str.) vertexalis Li Yin, sp. nov. and Syndicus (Semisyndicus) wangjisheni Li Yin, sp. nov. of the subfamily Scydmaeninae, and Tmesiphorus tanglimontis Li Yin, sp. nov. and Tribasodites tubericeps Li Yin, sp. nov. of the subfamily Pselaphinae. Illustrations of the habitus and major diagnostic characters of each new species are provided.
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Besouros , Distribuição Animal , Estruturas Animais , Animais , ChinaRESUMO
Ischemic stroke is a disease caused by insufficient blood and oxygen supply to the brain, which is mainly due to intracranial arterial stenosis and middle cerebral artery occlusion. Exosomes play an important role in cerebral ischemia. Nucleic acid substances such as miRNA, circRNA, lncRNA in exosomes can play communication roles and improve cerebral ischemia by regulating the development and regeneration of the nervous system, remodeling of blood vessels and inhibiting neuroinflammation. Furthermore, exosomes modulate stroke through various mechanisms, including improving neural communication, promoting the development of neuronal cells and myelin synapses, neurovascular unit remodeling and maintaining homeostasis of the nervous system. At the same time, exosomes are also a good carrier of bioactive substances, which can be modified and targeted to the lesion site. Here, we review the roles of exosomes in cerebral ischemia, and discuss the possible mechanisms and potentials of modification of exosomes for targeting stroke, providing a new idea for the prevention and treatment of cerebral ischemia.
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Isquemia Encefálica/tratamento farmacológico , Exossomos/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Doenças Neuroinflamatórias/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Exossomos/patologia , Humanos , Neurônios/efeitos dos fármacos , Neurônios/patologiaRESUMO
The Ctenistini fauna of China is insufficient documented. In this paper the first Chinese species of the genus Ctenisomorphus Raffray, 1890, C. yinggelingensis sp. nov., is described and separated from congeners based on two male and four female specimens collected at Yinggeling Natural Reserve, Hainan Island, southern China. Images of the habitus and major diagnostic characters of the new species are provided. The taxonomic status of Largeyeus anhuianus J.-K. Li, 1993 distributed in Anhui, eastern China is discussed, and the genus is placed as a junior synonym of Poroderus Sharp, 1883 syn. nov., resulting in P. anhuianus comb. nov.
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Besouros , Distribuição Animal , Estruturas Animais , Animais , China , Feminino , MasculinoRESUMO
A new species of the primarily Australasian genus Eupines King, 1866, E. crinita Li, Nomura Yin, sp. nov., is described from China and Japan, which is also the first record of the genus from the former country. Moreover, a new distributional record of E. sphaerica (Motschulsky, 1851) from China is provided.
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Besouros/classificação , Animais , China , JapãoRESUMO
Cerebral ischemia is a disease of ischemic necrosis of brain tissue caused by intracranial artery stenosis or occlusion and cerebral artery embolization. Neuroinflammation plays an important role in the pathophysiology of cerebral ischemia. Microglia, astrocytes, leukocytes and other cells that release a variety of inflammatory factors involved in neuroinflammation may play a damaging or protective role during the process of cerebral ischemia. TP53-induced glycolysis and apoptotic regulators (TIGAR) may facilitate the production of nicotinamide adenine dinucleotide phosphoric acid (NADPH) via the pentose phosphate pathway (PPP) to inhibit oxidative stress and neuroinflammation. TIGAR can also directly inhibit NF-κB to inhibit neuroinflammation. TIGAR thus protect against cerebral ischemic injury. Exogenous NADPH can inhibit neuroinflammation by inhibiting oxidative stress and regulating a variety of signals. However, since NADPH oxidase (NOX) may use NADPH as a substrate to generate reactive oxygen species (ROS) to mediate neuroinflammation, the combination of NADPH and NOX inhibitors may produce more powerful anti-neuroinflammatory effects. Here, we review the cells and regulatory signals involved in neuroinflammation during cerebral ischemia, and discuss the possible mechanisms of targeting neuroinflammation in the treatment of cerebral ischemia with TIGAR/NADPH axis, so as to provide new ideas for the prevention and treatment of cerebral ischemia.
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Proteínas Reguladoras de Apoptose/genética , Isquemia Encefálica/tratamento farmacológico , NADP/genética , Doenças Neuroinflamatórias/tratamento farmacológico , Monoéster Fosfórico Hidrolases/genética , Animais , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Isquemia Encefálica/patologia , Humanos , NADP/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
The present study investigates legacy and novel brominated flame retardants (BFRs) in atmospheric PM2.5 associated with various urban source sectors in a city and electronic waste (e-waste) recycling facilities in southern China. The concentrations of polybrominated diphenyl ethers (PBDEs) and novel BFRs (∑2NBFRs) at the urban industrial park (UIP) sites varied greatly from 22.0 to 105 pg m-3 and from to 29.7 to 459 pg m-3, respectively, and higher concentrations were generally found at sites involving industrial sectors of electronics, plastics, and machinery. Their spatial variations at other urban potential source sites were small suggesting a lack of strong point emissions. The levels of PBDEs and ∑2NBFRs at the e-waste facilities (220-2356 pg m-3 and 83.6-569 pg m-3) were significantly higher and did not temporally decline, indicating that improvement in e-waste recycling techniques does not significantly reduce emissions of PBDEs. NBFRs dominated the BFRs at the urban sites (55% on average), while PBDEs were still dominant (78%) at the e-waste sites. PBDE congener profiles in PM2.5 were substantially different from those in commercial mixtures. The congener profiles as well as their correlations suggested frequent formation of lower brominated PBDEs from degradation of highly brominated congeners in this region, which became appreciable due to the reduced emissions. The significant correlations among the lower brominated congeners also reflected similar environmental behaviors due to similar physicochemical properties.
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Retardadores de Chama , China , Cidades , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Material Particulado/análiseRESUMO
Here, we elucidated the uptake and translocation of numerous halogenated organic compounds (HOCs) into corn and peanut throughout their life cycle cultivated in an agricultural field of an electronic waste recycling area, where plants were simultaneously exposed to contaminants in soil and ambient air. The geometric mean concentrations of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were 22.3 and 11.9 ng/g in peanut and 16.6 and 13.6 ng/g in corn, respectively. Decabromodiphenyl ethane (DBDPE, 6.07 ng/g) and dechlorane plus (DPs, 6.22 ng/g) also showed significant concentrations in peanuts. The plant uptake was initiated from root absorption at the emergence stage but it was subsequently surpassed by leaves absorption from the air since the late seedling stage or early reproductive stage. There was a rapid uptake of lower halogenated HOCs at the early vegetative stages in both species. However, robust uptake of highly halogenated compounds at the reproductive stages suggests a delayed accumulation of them by the plants. PBDE and PCB congener profiles suggest more noticeable tendency for inter-compartment translocation in peanut than in corn during the plant development. The DP and HBCD isomeric compositions in peanut (enriched with syn-DP and γ-HBCD) were different from those in the rhizosphere soils and air, suggesting a more stereoisomer-selective uptake and/or biotransformation in this species compared to corn. The bioaccumulation factors for root-soil and stem-root of these HOCs in most cases were <1. The tissue-distributions demonstrated that leaves serve as a significant reservoir of absorbed HOCs under the field conditions, whereas the low concentrations in peanut and corn kernels indicated translocation of most HOCs into this compartment was significantly hindered (especially for highly halogenated compounds).
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Resíduo Eletrônico , Retardadores de Chama/análise , Bifenilos Policlorados/análise , Arachis , China , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Zea maysRESUMO
Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein-protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.
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Processamento Alternativo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Feminino , Redes Reguladoras de Genes , Humanos , PrognósticoRESUMO
BACKGROUND: The miR-191-5p expression has been reported to increase in hepatocellular carcinoma (HCC), but its clinical value and exact role remain to be further clarified. Thus, a comprehensive analysis was performed in the current study to explore the underlying function of miR-191-5p in HCC. METHODS: HCC-related expression data were collected to conduct a thorough analysis to determine the miR-191-5p expression and its clinical significance in HCC, including microarray data from the Gene Expression Omnibus and ArrayExpress database as well as quantitative real-time polymerase chain reaction (qRT-PCR) data of 178 matched clinical samples. The underlying relationship between miR-191-5p and HCC was also explored on the basis of a series of bioinformatics analyses. RESULTS: The overall pooled meta-analysis showed an overexpression of miR-191-5p in the HCC samples (SMD=0.400, 95% CI=0.139-0.663, P=0.003), consistent with the detected result of the clinical HCC samples through the qRT-PCR analysis. Higher miR-191-5p levels were correlated with advanced TNM stages (III and IV), higher pathological grades, and metastasis. Functionally, 64 potential target genes were acquired for further mechanism analysis. Two pathways (p75 neurotrophin receptor and liver kinase B1-mediated signaling pathways), which were likely modulated by miR-191-5p, were regarded to be linked to the deterioration of HCC. Early growth response 1 and UBE2D3 were identified as the most likely targets for miR-191-5p in HCC and were commonly implied in the top enriched pathways and protein-protein network. CONCLUSIONS: In summary, miR-191-5p may function as a tumor promoter miRNA of HCC, and the miR-191-5p inhibitor may contribute to the targeted HCC treatment in the future.