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BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. METHODS: Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. RESULTS: Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. CONCLUSIONS: These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.
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INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).
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Lattice-oxygen activation has emerged as a popular strategy for optimizing the performance and selectivity of oxide-based thermocatalysis and electrolysis. However, the significance of lattice oxygen in oxide photocatalysts has been ignored, particularly in gas-solid reactions. Here, using methane oxidation over a Ru1@ZnO single-atom photocatalyst as the prototypical reaction and via 18O isotope labelling techniques, we found that lattice oxygen can directly participate in gas-solid reactions. Lattice oxygen played a dominant role in the photocatalytic reaction, as determined by estimating the kinetic constants in the initial stage. Furthermore, we discovered that dynamic diffusion between O2 and lattice oxygen proceeded even in the absence of targeted reactants. Finally, single-atom Ru can facilitate the activation of adsorbed O2 and the subsequent regeneration of consumed lattice oxygen, thus ensuring high catalyst activity and stability. The results provide guidance for next-generation oxide photocatalysts with improved activities and selectivities.
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Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism.
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Lactobacillus fermentum can exert antiaging effects, but their roles are strain-specific, and little is known about the molecular mechanisms in some strains. This study investigated the antiaging effects of L. fermentum WC2020 (WC2020) isolated from Chinese fermented pickles and the underlying mechanism of the action in Caenorhabditis elegans. WC2020 enhanced the mean lifespan of L1-stage and L4-stage worms by 22.67% and 12.42%, respectively, compared with Escherichia coli OP50 (OP50), a standard food source for C. elegans. WC2020-induced longevity was accompanied by an increase in body length and mitochondrial transmembrane potential and a reduction in lipid accumulation and the production of reactive oxygen species and malondialdehyde. Moreover, WC2020 increased the production of glutathione, superoxide dismutases, and catalases and altered the transcripts of many phenotype-related genes. Furthermore, WC2020-fed jnk-1 rather than akt-2 or pmk-1 loss-of-function mutants showed similar lifespans to OP50-fed worms. Correspondingly, WC2020 significantly upregulated the expression of jnk-1 rather than genes involved in insulin-like, p38 MAPK, bate-catenin, or TGF-beta pathway. Moreover, the increase in body length, mitochondrial transmembrane potential, and antioxidant capability and the decrease in lipid accumulation induced by WC2020 were not observed in jnk-1 mutants. Additionally, WC2020 increased the expression of daf-16 and the proportion of daf-16::GFP in the nucleus, and increased lifespan disappeared in WC2020-fed daf-16 loss-of-function mutants. In conclusion, WC2020 activated the JNK/DAF-16 pathway to improve mitochondria function, reduce oxidative stress, and then extend the longevity of nematodes, suggesting WC2020 could be a potential probiotic targeting JNK-mediated antioxidant pathway for antiaging in food supplements and bioprocessing. PRACTICAL APPLICATION: Aging has a profound impact on the global economy and human health and could be delayed by specific diets and nutrient resources. This study demonstrated that Lactobacillus fermentum WC2020 could be a potential probiotic strain used in food to promote longevity and health via the JNK-mediated antioxidant pathway.
Subject(s)
Antioxidants , Caenorhabditis elegans Proteins , Caenorhabditis elegans , Limosilactobacillus fermentum , Longevity , Animals , Caenorhabditis elegans/physiology , Limosilactobacillus fermentum/physiology , Antioxidants/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Oxidative Stress , Reactive Oxygen Species/metabolism , Signal Transduction , MAP Kinase Signaling System , Membrane Potential, Mitochondrial , Mitogen-Activated Protein KinasesABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong Decotion (XQLD) is a commonly used Chinese herbal formula in clinical practice, especially for allergic diseases such as asthma. However, its intrinsic mechanism for the treatment of neutrophilic asthma (NA) remains unclear. AIM OF THE STUDY: The aim of this study was to evaluate the efficacy and potential mechanisms of XQLD on NA using network pharmacology and in vivo experiments. MATERIALS AND METHODS: First, the active compounds, potential targets and mechanisms of XQLD against NA were initially elucidated by network pharmacology. Then, OVA/CFA-induced NA mice were treated with XQLD to assess its efficacy. Proteins were then analyzed and quantified using a Tandem Mass Tags approach for differentially expressed proteins (DEPs) to further reveal the mechanisms of NA treatment by XQLD. Finally, the hub genes, critical DEPs and potential pathways were validated. RESULTS: 176 active compounds and 180 targets against NA were identified in XQLD. Protein-protein interaction (PPI) network revealed CXCL10, CX3CR1, TLR7, NCF1 and FABP4 as hub genes. In vivo experiments showed that XQLD attenuated inflammatory infiltrates, airway mucus secretion and remodeling in the lungs of NA mice. Moreover, XQLD significantly alleviated airway neutrophil inflammation in NA mice by decreasing the expression of IL-8, MPO and NE. XQLD also reduced the levels of CXCL10, CX3CR1, TLR7, NCF1 and FABP4, which are closely associated with neutrophil inflammation. Proteomics analysis identified 28 overlapping DEPs in the control, NA and XQLD groups, and we found that XQLD inhibited ferroptosis signal pathway (elevated GPX4 and decreased ASCL3) as well as the expression of ARG1, MMP12 and SPP1, while activating the Rap1 signaling pathway. CONCLUSION: This study revealed that inhibition of ARG1, MMP12 and SPP1 expression as well as ferroptosis pathways, and activation of the Rap1 signaling pathway contribute to the therapeutic effect of XQLD on NA.
Subject(s)
Asthma , Drugs, Chinese Herbal , Network Pharmacology , Proteomics , Animals , Asthma/drug therapy , Drugs, Chinese Herbal/pharmacology , Mice , Protein Interaction Maps , Female , Neutrophils/drug effects , Neutrophils/metabolism , Mice, Inbred BALB C , Lung/drug effects , Lung/metabolism , Lung/pathology , Anti-Asthmatic Agents/pharmacology , Disease Models, Animal , Ovalbumin , MaleABSTRACT
BACKGROUND: Establishment of a reliable prognostic model and identification of novel biomarkers are urgently needed to develop precise therapy strategies for clear cell renal cell carcinoma (ccRCC). Stress response stated T cells (Tstr) are a new T-cell subtype, which are related to poor disease stage and immunotherapy response in various cancers. METHODS: 10 machine-learning algorithms and their combinations were applied in this work. A stable Tstr-related score (TCs) was constructed to predict the outcomes and PD-1 blockade treatment response in ccRCC patients. A nomogram based on TCs for personalized prediction of patient prognosis was constructed. Functional enrichment analysis and TimiGP algorithm were used to explore the underlying role of Tstr in ccRCC. The key TCs-related gene was identified by comprehensive analysis, and the bioinformatics results were verified by immunohistochemistry using a tissue microarray. RESULTS: A robust TCs was constructed and validated in four independent cohorts. TCs accurately predicted the prognosis and PD-1 blockade treatment response in ccRCC patients. The novel nomogram was able to precisely predict the outcomes of ccRCC patients. The underlying biological process of Tstr was related to acute inflammatory response and acute-phase response. Mast cells were identified to be involved in the role of Tstr as a protective factor in ccRCC. TNFS13B was shown to be the key TCs-related gene, which was an independent predictor of unfavorable prognosis. The protein expression analysis of TNFSF13B was consistent with the mRNA analysis results. High expression of TNFSF13B was associated with poor response to PD-1 blockade treatment. CONCLUSIONS: This study provides a Tstr cell-related score for predicting outcomes and PD-1 blockade therapy response in ccRCC. Tstr cells may exert their pro-tumoral role in ccRCC, acting against mast cells, in the acute inflammatory tumor microenvironment. TNFSF13B could serve as a key biomarker related to TCs.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Machine Learning , Carcinoma, Renal Cell/immunology , Humans , Kidney Neoplasms/immunology , Prognosis , Male , Female , Nomograms , Biomarkers, Tumor/metabolism , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , T-Lymphocytes/immunologyABSTRACT
BACKGROUND: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. METHODS: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. RESULTS: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PDL1 of A549 cells stimulated by IFNγ as well. CONCLUSION: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR.
Subject(s)
Antineoplastic Agents , Coix , Lung Neoplasms , Programmed Cell Death 1 Receptor , Signal Transduction , Humans , A549 Cells , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Drug Synergism , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Protein Interaction Maps/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , Coix/chemistry , Antineoplastic Agents/pharmacologyABSTRACT
Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.
Subject(s)
Asthma , Matrix Metalloproteinase 9 , Animals , Mice , Humans , Matrix Metalloproteinase 9/genetics , Lipopolysaccharides , Asthma/drug therapy , Asthma/genetics , Bronchi , Gene Expression ProfilingABSTRACT
Successful male reproductive development is the guarantee for sexual reproduction of flowering plants. Male reproductive development is a complicated and multi-stage process that integrates physiological processes and adaptation and tolerance to a myriad of environmental stresses. This well-coordinated process is governed by genetic and epigenetic machineries. Non-coding RNAs (ncRNAs) play pleiotropic roles in the plant growth and development. The identification, characterization and functional analysis of ncRNAs and their target genes have opened a new avenue for comprehensively revealing the regulatory network of male reproductive development and its response to environmental stresses in plants. This review briefly addresses the types, origin, biogenesis and mechanisms of ncRNAs in plants, highlights important updates on the roles of ncRNAs in regulating male reproductive development and emphasizes the contribution of ncRNAs, especially miRNAs and lncRNAs, in responses to abiotic stresses during this unique process in flowering plants.
Subject(s)
Magnoliopsida , MicroRNAs , RNA, Long Noncoding , Magnoliopsida/genetics , Gene Expression Regulation, Plant/genetics , RNA, Untranslated/genetics , Stress, Physiological/genetics , Plants/genetics , MicroRNAs/genetics , RNA, Long Noncoding/geneticsABSTRACT
Oligodendrocytes (OLs) form myelin sheaths around axons in the central nervous system (CNS) facilitate the propagation of action potentials. The studies have shown that the differentiation and maturation of OLs involve microRNA (miR) regulation. The recent findings have addressed that miR-204 regulates OL differentiation in culture. In this study, through in situ hybridization in combination with immunohistochemistry, we showed that microRNA-204-5p in the corpus callosum was mainly expressed in OLs immunoreactive with adenomatous polyposis coli (APC), an OL marker. We also found miR-204-5p expression in mature OLs was suppressed by the addition of interleukin-6 (IL-6). Moreover, IL-6-induced inhibition of miR-204-5p expression was blocked by the addition of the inhibitors specific for p38 mitogen-activated protein kinase (p38MAPK) or phosphatidylinositol 3-kinase (PI3K) pathway. We further utilized a rat model by feeding cuprizone (CPZ)-containing diet for 3 weeks to induce demyelination and gliosis in the corpus callosum, as well as the upregulation of IL-6 gene expression significantly. Despite that miR-204-5p expression in the corpus callosum was not altered after feeding by CPZ for 3 weeks, its expression was increased and IL-6 transcription was decreased in the corpus callosum of the recovery group that was fed by CPZ for the first 2 weeks and by the regular diet for one more week. Our data demonstrate that miR-204-5p expression in OLs declined under the influence of the inflamed microenvironment. The findings that an increase in miR-204-5p and declined IL-6 expression observed in the recovery group might be involved with OL repair in the corpus callosum, and also shed light on a potential role for miR-204-5p in OL homeostasis following the white matter injury.
Subject(s)
Interleukin-6 , MicroRNAs , Rats , Animals , Mice , Interleukin-6/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Oligodendroglia/metabolism , Myelin Sheath/metabolism , MicroRNAs/genetics , Cuprizone/pharmacology , Cell Differentiation , Mice, Inbred C57BLABSTRACT
Our prior investigations have demonstrated the pivotal role of IL-33 in facilitating the maturation of oligodendrocytes (OLs), prompting our interest in exploring its potential therapeutic effects. In this study, our focus was directed towards deciphering the functions of interleukin-33 (IL-33) in established demyelinating mouse model induced by the feeding of cuprizone (CPZ)-containing diet. We observed the reduction in corpus callosal adenomatous polyposis coli (APC)+ OLs with IL-33 expression in mice subjected to CPZ feeding for durations of 6 and 8 weeks. In parallel, the levels of IL-33 in the corpus callosum declined after CPZ-containing diet. Furthermore, we conducted experiments utilizing primary oligodendrocyte precursor cells (OPCs) and mature OLs, which were exposed to CPZ. A decrease in the expression of myelin basic protein (MBP) was evident in the cultures of mature OLs after treatment with CPZ. Additionally, both IL-33 mRNA and protein levels exhibited downregulation. To counteract the diminished IL-33 levels induced by CPZ, we employed a lentiviral vector to overexpress IL-33 in OLs. Intriguingly, the overexpression of IL-33 (IL33OE) in OLs resulted in a more distinct membranous morphology following CPZ treatment when compared to that observed in OL Mock cultures. Moreover, MBP protein levels in the presence of CPZ were higher in IL33OE OLs than that detected in OL Mock cultures. These findings collectively indicate that IL-33 possesses the capability to mitigate CPZ-induced damage and bolster OL homeostasis. In summary, our study underscores the importance of IL-33 in the context of demyelinating diseases, shedding light on its potential therapeutic implications for fostering remyelination and preserving OL function.
Subject(s)
Cuprizone , Demyelinating Diseases , Interleukin-33 , Animals , Mice , Corpus Callosum , Cuprizone/toxicity , Demyelinating Diseases/drug therapy , Disease Models, Animal , Interleukin-33/metabolism , Interleukin-33/pharmacology , Interleukin-33/therapeutic use , Mice, Inbred C57BL , Myelin Sheath , OligodendrogliaABSTRACT
Transparent conducting oxides are a critical component in modern (opto)electronic devices and solar energy conversion systems, and forming textured functional films on them is highly desirable for property manipulation and performance optimization. However, technologically important materials show varied crystal structures, making it difficult to establish coherent interfaces and consequently the oriented growth of these materials on transparent conducting oxides. Here, taking lattice-mismatched hexagonal α-Fe2O3 and tetragonal fluorine-doped tin oxide as the example, atomic-level investigations reveal that a coherent ordered structure forms at their interface, and via an oxygen-mediated dimensional and chemical-matching manner, that is, matched Voronoi cells of oxygen sublattices, [110]-oriented α-Fe2O3 films develop on fluorine-doped tin oxide. Further measurements of charge transport characteristics and photoelectronic effects highlight the importance and advantages of coherent interfaces and well-defined orientation in textured α-Fe2O3 films. Textured growth of lattice-mismatched oxides, including spinel Co3O4, fluorite CeO2, perovskite BiFeO3 and even halide perovskite Cs2AgBiBr6, on fluorine-doped tin oxide is also achieved, offering new opportunities to develop high-performance transparent-conducting-oxide-supported devices.
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Identification of molecular biomarkers associated with neutrophilic asthma (NA) phenotype may inform the discovery of novel pathobiological mechanisms and the development of diagnostic markers. Three mRNA transcriptome datasets extracted from induced sputum of asthma patients with various inflammatory types were used to screen for macrophage-related molecular mechanisms and targets in NA. Furthermore, the predicted targets were also validated on an independent dataset (N = 3) and animal model (N = 5). A significant increase in total cells, neutrophils and macrophages was observed in bronchoalveolar lavage (BAL) fluid of NA mice induced by ovalbumin/freund's adjuvant, complete (OVA/CFA). And we also found elevated levels of neutrophil and macrophage infiltration in NA subtype in external datasets. NA mice had increased secretion of IgE, IL-1ß, TNF-α and IL-6 in serum and BAL fluid. MPO, an enzyme present in neutrophils, was also highly expressed in NA mice. Then, weighted gene co-expression network analysis (WGCNA) identified 684 targets with the strongest correlation with NA, and we obtained 609 macrophage-related specific differentially expressed genes (DEGs) in NA by integrating macrophage-related genes. The top 10 genes with high degree values were obtained and their mRNA levels and diagnostic performance were then determined by RT-qPCR and receiver operator characteristic (ROC) analysis. Statistically significant correlations were found between macrophages and all key targets, with the strongest correlation between ITGAM and macrophages in NA. Double-Immunofluorescence staining further confirmed the co-localization of ITGAM and F4/80 in NA. ITGAM was identified as a critical target to distinguish NA from healthy/non-NA individuals, which may provide a novel avenue to further uncover the mechanisms and therapy of NA.
Subject(s)
Apoptosis , Asthma , Humans , Animals , Mice , Asthma/drug therapy , Asthma/genetics , Asthma/chemically induced , Neutrophils , Macrophages , RNA, Messenger/genetics , CD11b AntigenABSTRACT
Light-driven primary amine oxidation to imines integrated with H2 production presents a promising means to simultaneous production of high-value-added fine chemicals and clean fuels. Yet, the effectiveness of this strategy is generally limited by the poor charge separation of photocatalysts and uncontrolled hydrogenation of imines to secondary amines. Herein, a spatial decoupling strategy is proposed to isolate redox chemistry at distinct sites of photocatalysts, and CoP core-ZnIn2S4 shell (CoP@ZnIn2S4) coaxial nanorods are assembled as the proof-of-concept photocatalyst. Directional and ultrafast carrier separation occurs between the CoP core and the ZnIn2S4 shell, as confirmed by in situ X-ray photoelectron spectroscopy, surface photovoltage spectroscopy, and transient absorption spectroscopy analyses. Toward the photoconversion of model substrate benzylamine to N-benzylbenzaldimine, CoP@ZnIn2S4 exhibits a 48-time higher production rate and >99% selectivity when compared to ZnIn2S4 (ca. 20% selectivity), and the detailed reaction mechanism has been verified by in situ diffuse reflectance infrared Fourier transform spectroscopy.
ABSTRACT
The sustainable production of chemicals and fuels from abundant solar energy and renewable carbon sources provides a promising route to reduce climate-changing CO2 emissions and our dependence on fossil resources. Here, we demonstrate solar-powered formate production from readily available biomass wastes and CO2 feedstocks via photoelectrochemistry. Non-precious NiOOH/α-Fe2O3 and Bi/GaN/Si wafer were used as photoanode and photocathode, respectively. Concurrent photoanodic biomass oxidation and photocathodic CO2 reduction towards formate with high Faradaic efficiencies over 85% were achieved at both photoelectrodes. The integrated biomass-CO2 photoelectrolysis system reduces the cell voltage by 32% due to the thermodynamically favorable biomass oxidation over conventional water oxidation. Moreover, we show solar-driven formate production with a record-high yield of 23.3 µmol cm-2 h-1 as well as high robustness using the hybrid photoelectrode system. The present work opens opportunities for sustainable chemical and fuel production using abundant and renewable resources on earth-sunlight, biomass and CO2.
ABSTRACT
Since the outbreak of COVID-19, the pandemic has become an important topic of global public health. To reduce the rapid spread of the pandemic, compliance with preventive behaviors has become one of the important guidelines from the World Health Organization (WHO). Healthcare workers stand on the frontline for pandemic prevention, and preventive behaviors are essential measures to protect their health and safety. The purpose of this study was to propose an integrative model that explained and predicted COVID-19 preventive behaviors among healthcare workers. The study integrated workplace safety climate and the health belief model (HBM) to verify the impact of workplace safety climate and health belief factors on the safety attitude, safety compliance, and safety satisfaction of healthcare workers performing COVID-19 pandemic prevention behaviors. A cross-sectional study was conducted from March to August 2021 with a self-administered online questionnaire. The sample of the study was drawn from healthcare workers of a famous medical institution in Taipei City as research subjects. After collecting 273 valid questionnaires and verifying them through the analysis of structural equation modeling (SEM), the findings revealed that workplace safety climate had an impact on health belief factors, and then health belief factors had impacts on safety attitudes. In addition, safety attitude affected safety compliance, while safety compliance further affected safety satisfaction. The study showed that workplace safety climate can strengthen healthcare workers' health beliefs and further affect their safety attitudes, safety compliance, and safety satisfaction. The study attempted to propose a model of healthcare workers' pandemic prevention behaviors as a reference for medical facility administrators in real practice.
ABSTRACT
Zika virus (ZIKV) is a neurotropic flavivirus. The outbreak of ZIKV in 2016 created a global health emergency. However, the underlying pathogenic mechanisms remain elusive. We investigated the host response features of in vivo replication in a mouse model of ZIKV infection, by performing a series of transcriptomic and bioinformatic analyses of ZIKV and mock-infected brain tissue. Tissue damage, inflammatory cells infiltration and high viral replication were observed in the brain tissue of ZIKV infected mice. RNA-Seq of the brain indicated the activation of ferroptosis pathways. Enrichment analysis of ferroptosis regulators revealed their involvement in pathways such as mineral absorption, fatty acid biosynthesis, fatty acid degradation, PPAR signaling pathway, peroxidase, and adipokinesine signalling pathway. We then identified 12 interacted hub ferroptosis regulators (CYBB, HMOX1, CP, SAT1, TF, SLC39A14, FTL, LPCAT3, FTH1, SLC3A2, TP53, and SLC40A1) that were related to the differential expression of CD8+ T cells, microglia and monocytes. CYBB, HMOX1, SALT, and SLAC40A1 were selected as potential biomarkers of ZIKV infection. Finally, we validated our results using RT-qPCR and outside available datasets. For the first time, we proposed a possible mechanism of ferroptosis in brain tissue infected by ZIKV in mice and identified the four key ferroptosis regulators.
Subject(s)
Ferroptosis , Host-Pathogen Interactions , Zika Virus Infection , Zika Virus , Animals , Mice , 1-Acylglycerophosphocholine O-Acyltransferase , Cation Transport Proteins , CD8-Positive T-Lymphocytes , Disease Models, Animal , Fatty Acids , Ferroptosis/genetics , Ferroptosis/physiology , Transcriptome , Virus Replication , Zika Virus/pathogenicity , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/physiologyABSTRACT
PURPOSE: To evaluate whether traditional mind-body movement therapy (TMBM) can be used as a complementary or alternative therapy for exercise-based cardiopulmonary rehabilitation (EBCR) on chronic cardiopulmonary dyspnoea. METHODS: PubMed, Embase, Scopus, Web of Science and China National Knowledge Infrastructure were searched from their inception to 2 July 2021. Randomised clinical trials evaluating the effectiveness of TMBM versus EBCR, and TMBM +EBCR versus TMBM in the treatment of chronic cardiopulmonary dyspnoea were selected. The outcomes were exercise capacity (6 min walk distance, 6MWD) and quality of life (QoL). RESULTS: Thirty-four randomised clinical trials with 2456 patients were included. For TMBM vs EBCR alone, statistically significant improvements in the 6MWD favoured the TMBM for chronic obstructive pulmonary disease (COPD) (mean difference(MD)=12.22 m; 95% CI 5.94 to 18.50; I2=56%) and heart failure (HF) patients (MD=43.65 m; 95% CI 7.91 to 79.38; I2=0%). Statistically significant improvements in QoL also favoured TMBM over EBCR for patients with HF(MD=-9.19; 95% CI -11.05 to -7.32; I2=0%) but non-significant trend for COPD (standardised mean difference (SMD)=-0.31; 95% CI -0.62 to 0.01; I2=78%). Comparisons of TMBM +EBCR versus EBCR alone revealed significant improvements in the QoL for COPD (SMD=-0.52; 95% CI -0.94 to -0.10; I2=86%) and patients with HF (MD=-2.82; 95% CI -4.99 to -0.64; I2=0%). The 6MWD results favoured the TMBM +EBCR for patients with COPD (MD=16.76 m; 95% CI 10.24 to 23.29; I2=0%), but only showed a slight trend towards additional benefits of TMBM +EBCR in the HF studies (MD=13.77 m; 95% CI -1.01 to 28.54; I2=65%) . CONCLUSIONS: TMBM has positive effects on patients' 6MWD and QoL, with similar or even better effects than EBCR. It may be beneficial to use TMBM as a supplementary or alternative strategy for EBCR in treatment plans. PROSPERO REGISTRATION NUMBER: CRD42021241181.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Quality of Life , Humans , Exercise Therapy/methods , Pulmonary Disease, Chronic Obstructive/rehabilitation , Dyspnea/etiology , Dyspnea/therapy , Exercise , Randomized Controlled Trials as TopicABSTRACT
The infection of Nocardia gipuzkoensis is a relatively uncommon form of pulmonary nocardiosis seen in clinical patients. In general, nocardiosis tends to occur in patients with immune deficiency. Here, we report a 23-year-old female who was admitted to the hospital due to cough and sputum production over 10 years, diagnosed with bronchiectasis. The N. gipuzkoensis infection was identified by metagenomic next-generation sequencing and whole genome sequencing. Imipenem/cilastatin and compound sulfamethoxazole tablets were used to control the infection and the pulmonary inflammation subsided gradually.