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Hepatocellular carcinoma (HCC) represents a major global health concern, demanding a thorough understanding of its molecular mechanisms for effective therapeutic strategies. RNA-binding proteins (RBPs) play critical roles in post-transcriptional gene regulation, with their dysregulation increasingly recognized as a hallmark of various cancers. However, the specific contributions of RBPs to HCC pathogenesis and prevention remain incompletely understood. In this study, we systematically conducted an examination of the expression profiles and clinical relevance of RBPs in 556 clinical samples from well-established cohorts. Through comprehensive analyses, a subset of RBPs exhibiting significant overexpression in HCC was identified, establishing a noteworthy correlation between their aberrant expression and HCC progression. Furthermore, 40S ribosomal protein S5 (RPS5), a ribosomal protein, emerged as a potential key contributor in HCC progression. Rigorous analyses established a correlation between elevated RPS5 expression and advanced clinicopathological features, suggesting its potential as a prognostic biomarker. Experiments further confirmed the impact of RPS5 on pivotal cellular processes implicated in cancer progression, including cell proliferation and metastasis. Further mechanistic studies unveiled the potential of RPS5 to activate the cell cycle by binding to key molecules involved in the pathway, thereby promoting the malignant progression of HCC. Additionally, our analysis of the etiology behind RPS5 overexpression in HCC posited it as an outcome of transcriptional regulation by the transcription factors Nuclear Respiratory Factor 1 (NRF1) and MYC-associated zinc finger protein (MAZ). In conclusion, our study contributes to the growing evidence elucidating the intricate involvement of RBPs, exemplified by RPS5, in the malignant progression of HCC. The integration of genomic, transcriptomic, and functional analyses provides a comprehensive understanding of the regulatory mechanisms associated with RPS5 in HCC. This comprehensive analysis not only advances our knowledge of the molecular drivers behind HCC but also highlights the potential therapeutic relevance of targeting RBPs and their regulatory network for the development of more effective treatment strategies.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Ribossômicas/genética , Proteínas de Ligação a RNA/genéticaRESUMO
A transition-metal-free synthetic method of various ynones via decarboxylative alkynylation of α-keto acids is described. The reaction is carried out under mild conditions and exhibits remarkable tolerance of functional groups. The mechanism of a radical process is proposed in the reaction.
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Multiple pesticides are heavily applied in crops grown in China's tropics due to the prevalence of diseases and pests, thus posing potential risks to nontarget organisms (e.g., honeybees, lacewings, ladybugs, and humans). However, there is little information on this topic. This study is the first assessment of the occurrence, driving factors, and ecological/human health risks of 32 current-use pesticides (CUPs) in 10 frequently-planted crops collected from practicing rice-vegetable rotation systems in Hainan, China. Of the 132 whole crop samples, 44 (33.3 %) residues from ≥8 pesticides were detected in 9.09 % of crop samples with concentrations ≥0.5 mg kg-1. Six pesticide residues, namely carbendazim, pyraclostrobin, acetamiprid, thiophanate methyl, phoxim, and imidacloprid, were detected in 72.7 % of samples, with concentrations ranging from 0.0021 to 13.5 (median = 0.032) mg kg-1. Among them, carbendazim, pyraclostrobin, and acetamiprid were the most common, contributions from 10.2 to 25.5 % and a detection frequency ranging from 25.6 to 56.1 %. The order of total concentration of 32 CUPs (∑32 CUP) concentrations during the year was January > May > November > August and vegetables > rice, being highly related with pesticides usage pattern, crop type, plant accumulation/dissipation and plant lipid contents. The ecological risk quotients (RQs) to four beneficial terrestrial organisms showed that 9.6-39.1 % of samples posed a potential medium or high ecological risk, with 13.6-65.9 % of samples at ∑RQ > 1 being highly affected by the residues of neonicotinoids and emamectin benzoate. Emamectin benzoate (8.9 %) and acetamiprid (5.6 %) exceeded the individual Maximum Residue Levels based on Chinese legislation (GB2763-2021). Moreover, cumulative dietary exposure presented a higher risk to humans in 11.0 and 22.0 % of the cases for acute and chronic, mainly originating from the higher concentration contributors of systemic pesticides in edible crops. Therefore, the regulation and monitoring of CUP residues is imperative for rice-vegetable rotation systems in tropical China to avoid negative effects on nontarget organisms.
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Resíduos de Praguicidas , Praguicidas , Humanos , Animais , Abelhas , Praguicidas/análise , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Produtos Agrícolas , Verduras/química , China , Medição de RiscoRESUMO
OBJECTIVE: This study was designed to investigate the effects of cognitive-behavioral intervention (CBI) combined with integrated health care (IHC) on glycemic control, adverse mood, health knowledge and self-efficacy in patients with type 2 diabetes mellitus. METHODS: The clinical data of 115 patients with type 2 diabetes mellitus were retrospectively collected and divided into two groups according to the intervention methods, with 57 patients in group A receiving conventional care and 58 patients in group B receiving CBI combined with IHC. The blood glucose, scores of Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), health knowledge, self-efficacy, quality of life, and nursing satisfaction were compared between the two groups before and after intervention. RESULTS: Compared with group A, group B had lower glycated hemoglobin (HbAlc), 2-h postprandial glucose (2 hPG), and fasting plasma glucose (FPG) levels (P < 0.05), lower HAMD and HAMA scores (P < 0.05), higher health knowledge and self-efficacy scores (P < 0.05), and higher quality of life after intervention (P < 0.05). Group B exhibited a nursing satisfaction rate of 94.83%, higher than that of 70.18% in group A (P < 0.05). CONCLUSION: The effects of CBI combined with IHC can effectively control blood glucose and improve dysphoria, health knowledge, self-efficacy, and quality of life in patients with type 2 diabetes.
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This study explored the levels, sources, and risks of PAHs in soils from Yongle Atoll (YLA) and Xuande Atoll (XDA) of the Xisha Islands (XSIs) in the South China Sea, China, under different vegetation cover types and soil sources. The results clearly showed that the levels of 16 US EPA priority PAHs (Σ16PAHs) are relatively low in XDA and YLA, with concentrations ranging from not detected (ND) to 151 ng/g (average 15.7 ng/g) and ND to 5.8 ng/g (average 2.1 ng/g), respectively. Three- and four-ring PAHs (62.3% and 53.8%) were widely distributed in YLA and XDA. The average concentration of Σ16PAHs in soils with shrub cover was 1.4, 1.8, 4.8, and 5.0 times higher than that in soils with herbaceous cover, vegetable cover, arbor cover, and no plant cover, respectively. Source analysis using binary diagnostic ratios and the positive matrix factorization (PMF) model suggested that PAHs have similar sources (gasoline/coal combustion, coke production, and biomass combustion), but different contributions in native soil and introduced soil. Moreover, diesel-related vehicular emission was identified to be an additional source of PAHs in native soil. Pearson's correlations revealed strong relationships between PAHs and organic matter or total organic carbon. The cancer risk of PAHs varied among different vegetation cover types and soil sources, following the orders herbaceous cover > vegetable cover > shrub cover > arbor cover > no plant cover and introduced soil > mixed soil > native soil. Nevertheless, the risk remained lower than the risk threshold (10-6), suggesting low carcinogenesis risk in the two atolls. Our findings provide new evidence for the introduction of external vegetation/soil acting as a driver of changes in the characteristics of PAHs in islands, and also underline the negligibility of the PAH increase in soils in the South China Sea, China, from the perspective of health hazards.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , China , Carvão Mineral/análise , Monitoramento Ambiental/métodos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Solo , Poluentes do Solo/análise , VerdurasRESUMO
Carbonylation of nitroaromatics with CO is extensively investigated with efficient but precious group 8-10 metal-based catalysts for the productions of both industrially and academically important chemicals such as isocyanates, formamides, carbamates, ureas and several types of heterocyclic compounds. Herein, we report that rationally designed nitrogen-doped carbon nanotubes (N-CNTs) exhibit catalytic activity toward CO activation for carbonylation of nitroaromatics to benzimidazolinones and ureas. Under the optimal conditions, N-CNT-promoted intramolecular carbonylation of 2-nitroaniline (1a) with CO leads to formation of 1,3-dihydro-2H-benzo[d]imidazol-2-one in 90% yield. Moreover, an intermolecular carbonylation of nitrobenzene and aniline with CO in the presence of the N-CNT gives 70% yield of N,N'-diphenylurea. The N-CNT is also applicable to various benzimidazolinones and phenyl ureas; moreover, it can be readily reused at least 9 times for the carbonylation. The theoretical investigation based on density functional theory calculations indicates that the graphitic N of the N-CNT plays a crucial step in the 1a reduction with CO. The correlation between the structural defect and catalytic performance of the N-CNT reveals an enhanced catalytic activity of the N-CNT with its increased structural defects. This research thus represents a major breakthrough in CO activation for nitroaromatic carbonylation with environmental-friendly, low-cost, and carbon-based catalysts as a potential alternative to expensive and scarce noble-metal-based catalysts.
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Chemical transformation of carbon dioxide (CO2) into fine chemicals such as oxazolidinones and carbamates is mainly reported using transition-metal complexes as homogeneous catalysts. Herein, we demonstrate that a heterogeneous catalyst of highly dispersed Cu (Cu/NHPC) supported on hierarchically porous N-doped carbon (NHPC) can efficiently promote CO2 fixations to oxazolidinones and ß-oxopropylcarbamates. The obtained NHPC, assembled by ultrathin nitrogen-doped carbon nanosheets with a three-dimensional (3D) structure, is readily prepared by pyrolysis of a nitrogen-containing polymer gel (NPG) in the presence of an activator of potassium bicarbonate (KHCO3). The resulting NHPC shows specific Brunauer-Emmet-Teller (BET) surface areas up to 2054 m2 g-1 with a mean micro/mesopore size of 0.55/3.2 nm and a broad macropore size distribution from 50 to 230 nm. The Cu/NHPC can efficiently promote three-component coupling of CO2, amines, and propargyl alcohols for syntheses of various oxazolidinones and ß-oxopropylcarbamates with yields up to 99% and a wide substrate scope. Moreover, the Cu/NHPC exhibits excellent recyclability in CO2-to-oxazolidinone transformation during nine-time recycling. The research thus develops an NHPC-based heterogeneous Cu catalyst for green transformation of CO2.