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Molybdenum disulfide (MoS2) is heralded as an exemplary two-dimensional (2D) functional material, largely attributed to its distinctive layered structure. Upon forming heterojunctions with reducing species, MoS2 displays remarkable photocatalytic properties. In this research, we fabricated a novel heterojunction photocatalyst, FeS/MoS2-0.05, through the integration of FeS with hollow MoS2. This composite aims at the efficient photocatalytic reduction of hexavalent chromium (Cr(VI)). A comprehensive array of characterization techniques unveiled that MoS2 flakes, dispersed on FeS, provide numerous active sites for photocatalysis at the heterojunction interface. The inclusion of FeS seemingly promotes the formation of sulfur vacancies on MoS2. Consequently, this heterojunction catalyst exhibits photocatalytic activity surpassing pristine MoS2 by a factor of 3.77. The augmented activity of the FeS/MoS2-0.05 catalyst is attributed chiefly to an internal electric field at the interface. This field enhances the facilitation of charge transfer and separation significantly. Density functional theory (DFT) calculations, coupled with experimental analyses, corroborate this observation. Additionally, DFT calculations indicate that sulfur vacancies act as pivotal sites for Cr(VI) adsorption. Significantly, the adsorption energy of Cr(VI) species shows enhanced favorability under acidic conditions. Our results suggest that the FeS/MoS2-0.05 heterojunction photocatalyst presents substantial potential for the remediation of Cr(VI)-contaminated wastewater.
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Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.
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Artrite Reumatoide , Perfilação da Expressão Gênica , Transcriptoma , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Humanos , Antirreumáticos/uso terapêutico , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Biomarcadores , Linfócitos T CD8-Positivos/imunologiaRESUMO
BACKGROUND: Genome-wide association studies (GWAS) have revealed numerous loci associated with multiple sclerosis (MS). However, the challenge lies in deciphering the mechanisms by which these loci influence the target traits. Here, we employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for MS. METHODS: We systematically integrated MS GWAS data (N = 115,803) with human plasma proteome data (N = 7213) and conducted proteome-wide association studies (PWAS) to identify MS-associated pathogenic proteins. Following this, we employed Mendelian randomization and Bayesian colocalization analyses to verify the causal relationship between these significant plasma proteins and MS. Lastly, we utilized the Drug-Gene Interaction Database (DGIdb) to identify potential drug targets for MS. RESULTS: The PWAS identified 25 statistically significant cis-regulated plasma proteins associated with MS at a false discovery rate of P < 0.05. Further analysis revealed that the abundance of 7 of these proteins (PLEK, TNXB, CASP3, CD59, CR1, TAPBPL, ATXN3) was causally related to the incidence of MS. Our findings indicated that genetically predicted higher levels of TNXB and CD59 were associated with a lower risk of MS, whereas higher levels of PLEK, CASP3, CR1, TAPBPL, and ATXN3 were associated with an increased risk of MS. Three plasma proteins (PLEK, CR1, CD59) were validated by colocalization analysis. Among these, CR1 was prioritized as a target for Eculizumab due to its significant association with MS risk. Additionally, PLEK, CR1, and CD59 were identified as druggable target genes. CONCLUSIONS: Our proteomic analysis has identified PLEK, CR1, and CD59 as potential drug targets for MS treatment. Developing pharmacological inducers or inhibitors for these proteins could pave the way for new therapeutic approaches, potentially improving outcomes for MS patients.
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Estudo de Associação Genômica Ampla , Esclerose Múltipla , Proteoma , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Esclerose Múltipla/sangue , Teorema de Bayes , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/genética , Análise da Randomização Mendeliana , Antígenos CD59/genética , Predisposição Genética para Doença , Proteômica/métodosRESUMO
BACKGROUND: Acute lung injury (ALI) is characterized by acute pulmonary inflammatory infiltration. Alveolar epithelial cells (AECs) release numerous pro-inflammatory cytokines, which result in the pathological changes seen in ALI. Ophiopogonin D (OD), extracted from the roots of Ophiopogon japonicus (Thunb.) Ker Gawl. (Liliaceae), reduces inflammation; however, the efficacy of OD in ALI has not been reported and the underlying molecular mechanisms remain unclear. PURPOSE: This study investigated the anti-inflammatory effects of OD, as well as the underlying mechanisms, in AECs and a mouse ALI model. METHODS: Lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were used to stimulate macrophages and A549 cells, and a mouse ALI model was established by intratracheal LPS administration. The anti-inflammatory effects and mechanisms of OD in the TNF-α-induced in vitro inflammation model was evaluated using real-time quantitative polymerase chain reaction qPCR), enzyme-linked immunosorbent assay (ELISA), western blotting, nuclear and cytoplasmic protein extraction, and immunofluorescence. The in vivo anti-inflammatory activity of OD was evaluated using hematoxylin and eosin staining, qPCR, ELISA, and western blotting. RESULTS: The bronchoalveolar lavage fluid and lung tissue of LPS-induced ALI mice exhibited increased TNF-α expression. TNF-α induced a significantly greater pro-inflammatory effect in AECs than LPS. OD reduced inflammation and mitogen-activated protein kinase (MAPK) and transcription factor p65 phosphorylation in vivo and in vitro and promoted signal transducer and activator of transcription 3 (STAT3) phosphorylation and A20 expression, thereby inducing apoptosis signal-regulating kinase 1 (ASK1) proteasomal degradation. CONCLUSION: OD exerts an anti-inflammatory effect by promoting STAT3-dependent A20 expression and ASK1 degradation. OD may therefore have therapeutic value in treating ALI and other TNF-α-related inflammatory diseases.
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Lesão Pulmonar Aguda , Anti-Inflamatórios , Lipopolissacarídeos , Fator de Transcrição STAT3 , Saponinas , Espirostanos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Saponinas/farmacologia , Espirostanos/farmacologia , Camundongos , Fator de Transcrição STAT3/metabolismo , Humanos , Anti-Inflamatórios/farmacologia , Masculino , MAP Quinase Quinase Quinase 5/metabolismo , Células A549 , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa/metabolismo , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Ophiopogon/química , Inflamação/tratamento farmacológico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Raízes de Plantas/químicaRESUMO
Wounding stress induces the biosynthesis of various secondary metabolites in plants, including anthocyanin. However, the underlying molecular mechanism remains elusive. Here, we reported that a transcription factor, VvWRKY5, promotes wounding-induced anthocyanin accumulation in grape (Vitis vinifera). Biochemical and molecular analyses demonstrated that wounding stress significantly increased anthocyanin content, and VvMYBA1 plays an essential role in this process. VvWRKY5 could interact with VvMYBA1 and amplify the activation effect of VvMYBA1 on its target gene VvUFGT. The transcript level of VvWRKY5 was notably induced by wounding treatment. Moreover, our data demonstrated that VvWRKY5 could promote the synthesis of jasmonic acid (JA), a phytohormone that acts as a positive modulator in anthocyanin accumulation, by directly binding to the W-box element in the promoter of the JA biosynthesis-related gene VvLOX and enhancing its activities, and this activation was greatly enhanced by the VvWRKY5-VvMYBA1 protein complex. Collectively, our findings show that VvWRKY5 plays crucial roles in wounding-induced anthocyanin synthesis in grape and elucidates the transcriptional regulatory mechanism of wounding-induced anthocyanin accumulation.
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Nanosilvers with multifarious morphologies have been extensively used in many fields, but their morphology-dependent toxicity toward nontarget aquatic organisms remains largely unclear. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the toxicological effects of silver nanomaterials with various morphologies on spatially resolved lipid profiles within multiple organs in adult zebrafish, especially for the gill, liver, and intestine. Integrated with histopathology, enzyme activity, accumulated Ag contents and amounts, as well as MSI results, we found that nanosilvers exhibit morphology-dependent nanotoxicity by disrupting lipid levels and producing oxidative stress. Silver nanospheres (AgNSs) had the highest toxicity toward adult zebrafish, whereas silver nanoflakes (AgNFs) exhibited greater toxicity than silver nanowires (AgNWs). Levels of differential phospholipids, such as PC, PE, PI, and PS, were associated with nanosilver morphology. Notably, we found that AgNSs induced greater toxicity in multiple organs, such as the brain, gill, and liver, while AgNWs and AgNFs caused greater toxicity in the intestine than AgNSs. Lipid functional disturbance and oxidative stress further caused inflammation and membrane damage after exposure to nanosilvers, especially with respect to sphere morphology. Taken together, these findings will contribute to clarifying the toxicological effects and mechanisms of different morphologies of nanosilvers in adult zebrafish.
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Prata , Peixe-Zebra , Animais , Prata/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Nanopartículas Metálicas/toxicidade , Brânquias/efeitos dos fármacos , Fígado/efeitos dos fármacosRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1006851.].