RESUMO
Background: To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk. Methods: By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results. Results: Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility. Conclusion: In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.
Assuntos
Doenças Autoimunes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/epidemiologia , Doenças Autoimunes/genética , Doenças Autoimunes/epidemiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein-protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas Experimentais , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteômica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Dietilnitrosamina/efeitos adversos , Cirrose Hepática/patologia , Modelos Animais de Doenças , Proteínas de Ligação a Ácido GraxoRESUMO
BACKGROUND: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. METHODS: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. RESULTS: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. CONCLUSION: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.
Assuntos
Células-Tronco Hematopoéticas , Células de Kupffer , Camundongos , Animais , Fígado , Monócitos , InflamaçãoRESUMO
OBJECTIVE: To assess the efficacy and safety of retention enema with traditional Chinese medicine (TCM) for ulcerative colitis (UC) through a meta-analysis of published studies. METHODS: Literatures were retrieved from five electronic databases. Quality evaluation and meta-analysis were respectively conducted using the Cochrane collaboration and RevMan5.3. Overall quality of evidence was evaluated using GRADE system. Effect sizes were pooled using random effect models. RESULTS: Seventeen RCTs were included. Compared with routine pharmacotherapies (RPs), TCM enema exhibited a statistically significant difference in clinical efficacy and reduction of the recurrence rate. The results of qualitative description for other endpoints, such as improvements in anabrosis, ulcer, diarrhea, and hematochezia, suggested that TCM enema had better efficacy than RPs. Furthermore, the incidence of side effects in TCM was lower than that in RPs. CONCLUSION: This meta-analysis confirmed the efficacy and safety of TCM enema for improving UC symptoms. However, further well-designed researches are needed.
Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Enema , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Myeloid cells infiltrate into the liver and differentiate into macrophages in different liver injury mouse models. However, the heterogeneity of bone marrow (BM)-derived LMs populations remains to be understood. To investigate this and understand the impact of the macrophage niche on the properties of recruited BM-derived macrophages, we used a non-myeloablation BM transplantation model to label and trace BM-derived LMs. Subsequently, we quantified the number of embryonic-derived liver-resident macrophages, BM-derived LMs and total LMs in CCl4 and irradiated acute liver injury mouse models, respectively. Finally, we compared the cell fate, gene expression patterns, chemokine signals, and surface markers of irradiated and CCl4 -treated BM-derived LMs. We observed that, as compared to CCl4, radiation generated a macrophage niche by depleting embryonic-derived liver-resident macrophages and induced the recruitment of BM-derived LMs that further settled in the liver. Irradiated and CCl4 -treated BM-derived LMs are different with respect to their cell fates, gene expression patterns, and chemokine expression and recruitment. They also have different surface markers shortly after differentiating from their progenitors. Our findings suggest that irradiated and CCl4 -treated LM populations derived from the bone marrow display different patterns of gene expression and phenotypes; these differences may be due to the availability of macrophage niche.
Assuntos
Células da Medula Óssea/metabolismo , Perfilação da Expressão Gênica/métodos , Fígado/citologia , Macrófagos/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos da radiação , Tetracloreto de Carbono/toxicidade , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Células Cultivadas , Ontologia Genética , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/genética , Falência Hepática Aguda/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/efeitos da radiação , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Fatores de TempoRESUMO
Exploring electrolytes of high safety is essential to pave the practical route for sodium-ion batteries (SIBs) toward their important applications in large-scale energy storage and power supplies. In this regard, ionogel electrolytes (IEs) have been highlighted owing to their high ionic conductivity, prominent electrochemical and thermal stability, and, more crucially, high interfacial wettability. However, present studies lack an understanding of the interaction of IEs, which determines the ion desolvation and migration. In this article, IEs comprising an SBA-15 host, an ionic liquid, sodium salt, and poly(vinylidene fluoride)-hexafluoro propylene (PVDF-HFP) have been proposed by mechanical ball milling and roller pressing. The component ratio has been optimized based on the balance between ionic conductivity and self-supporting capability of IEs. The optimal IEs showed sufficiently high ionic conductivity (2.48 × 10-3 S cm-1 at 30 °C), wide electrochemical window (up to 4.8 V vs Na+/Na), and high Na+ transference number (0.37). Due to the presence of SBA-15 and an ionic liquid, the IEs exhibited much improved thermal resistance than that of the conventional organic liquid electrolytes (OLEs). Furthermore, Fourier transform infrared (FT-IR) spectroscopy revealed the hydrogen bonding interaction between silanols and the dissolved salts, not only anchoring anions for immobilization but also promoting the dissociation of sodium salts. After being matched with the Na3V2(PO4)3 (NVP) cathode and metallic Na anode, the SIBs presented a specific discharge capacity of up to 110.7 mA h g-1 initially at room temperature with 92% capacity retention after 300 cycles. The improved safety and electrochemical performance provided insights into rationally regulating IEs and their interactions with the prospect of strengthening their practical applications in SIBs.
RESUMO
Design and synthesis of efficient electrocatalysts with low usage of precious metal and of high stability are essential for their practical applications in hydrogen evolution reactions. In this work, we synthesize an electrocatalyst through the deposition of platinum nanoparticles on defect-rich nitrogen-doped hollow carbon derived from surface-attached poly(4-vinylpyridine) monolayers. The platinum nanoparticles with an average diameter of about 1.8 nm are well dispersed on the outer surface of the pre-synthesized carbon material and the platinum loading is about 8.6 wt%. The mass activity of the as-synthesized catalyst under an overpotential of 55 mV is about 5.0 A mgPt -1, about 4.93 times higher than that of commercial Pt/C catalysts. Moreover, the synthesized catalyst is also more electrochemically stable than commercial Pt/C catalysts as evidenced by continuous cyclic voltammetry and chronoamperometric response measurements.
RESUMO
BACKGROUND: The identification of drug-target interactions is a crucial issue in drug discovery. In recent years, researchers have made great efforts on the drug-target interaction predictions, and developed databases, software and computational methods. RESULTS: In the paper, we review the recent advances in machine learning-based drug-target interaction prediction. First, we briefly introduce the datasets and data, and summarize features for drugs and targets which can be extracted from different data. Since drug-drug similarity and target-target similarity are important for many machine learning prediction models, we introduce how to calculate similarities based on data or features. Different machine learningbased drug-target interaction prediction methods can be proposed by using different features or information. Thus, we summarize, analyze and compare different machine learning-based prediction methods. CONCLUSION: This study provides the guide to the development of computational methods for the drug-target interaction prediction.
Assuntos
Descoberta de Drogas , Aprendizado de Máquina , Terapia de Alvo MolecularRESUMO
Alternative splicing (AS) is a transcriptional regulation mechanism that participates in multiple aspects of cancer. The present study aimed to identify differential AS events from tumor and nontumor samples and investigate the potential of AS as a source of candidate cancer diagnostic biomarkers. Deep RNA sequencing of three paired hepatocellular carcinoma (HCC) tumors and adjacent nontumors was applied to identify AS events. RTqPCR was performed on 45 HCC clinical samples to validate the splicing differences. The maximal information coefficient was first used to build an association between clinical features and AS changes. We identified 197 significantly differential skipped exon events, of which only 29% overlapped with the differentially expressed genes. The differentially spliced genes were mainly enriched in HCCcharacterized biological processes and pathways, clearly separating tumors from nontumors. We also validated the statistically significant splicing differences of three AS candidates (CEACAM1 exon 7, VPS29 exon 2 and ISOC2 exon 3). Furthermore, a clinicopathological analysis revealed that carcinoembryonic antigenrelated cell adhesion molecule 1 (CEACAM1) exon 7 was significantly correlated with the survival time, and VPS29 exon 2 was associated with cell differentiation stages. In conclusion, the findings of the three AS candidates in the present study could be beneficial in HCC prognosis and new treatment strategies.
Assuntos
Processamento Alternativo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/diagnóstico , Adulto , Antígenos CD/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Moléculas de Adesão Celular/genética , Éxons/genética , Feminino , Humanos , Hidrolases/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Isoformas de Proteínas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Análise de Sobrevida , Proteínas de Transporte Vesicular/genéticaRESUMO
Rational design and simple synthesis of carbon-based materials with high electrocatalytic activity are essential for their practical applications in electrochemical energy conversion and storage devices. Herein, we report the synthesis of nitrogen, sulfur co-doped three-dimensional interconnected hierarchically porous carbon (NSHPC) by zinc acetate assisted pyrolysis of polymer networks. The thus-synthesized NSHPC has a specific surface area of 1057 cm2 g-1 with the coexistence of micro- and meso-pores. As metal-free electrocatalyst, the NSHPC exhibits a promising activity towards oxygen reduction reactions as evidenced by the slightly negative shift of half-wave potential compared with commercial Pt/C catalyst. The assembled lithium ion battery using NSHPC as anode delivers the reversible capacity of 740 and 470 mA h g-1 at current densities of 2 and 5 A g-1 without performance decay after 1000 charge-discharge cycles. Moreover, the assembled supercapacitor using NSHPC as electrode has the capacitance of 203 F g-1 at 1 A g-1.
RESUMO
Imidazolium-based poly(ionic liquid) brushes were attached to spherical silica nanoparticles bearing various functionalities by using a surface-initiated atom transfer radical polymerization ("grafting from" technique). A temperature-programmed desorption process was applied to evaluate and analyze the carbon dioxide adsorption performance of the synthesized polymer brushes. The confined structure of the surface-attached polymer chains facilitates gas transport and adsorption, leading to an enhanced adsorption capacity of carbon dioxide molecules compared with pure polymer powders. Temperature-programmed desorption profiles of the synthesized polymer brushes after carbon dioxide adsorption reveal that the substituent groups on the nitrogen atom at the 3-position of the imidazole ring, as well as the associated anions significantly affect the adsorption capacity of functionalized poly(ionic liquid) brushes. Of the tested samples, amine-functionalized poly(ionic liquid) brushes associated with hexafluorophosphate ions exhibit the highest carbon dioxide adsorption capacity of 2.56â mmol g-1 (112.64â mg g-1 ) at 25 °C under a carbon dioxide partial pressure of 0.2â bar.
RESUMO
Layered double hydroxides (LDHs) are a new type of inorganic flame retardant additive for polymer nanocomposites. Although their unique structural properties and tunable chemical compositions make them highly promising, it has been noticed that on their own, LDHs can hardly fulfill all the requirements for commercial applications. In recent years, the application of LDHs together with other synergistic additives has been proposed as a new route for obtaining highly efficient flame retardant polymer nanocomposites. It is believed that the synergistic additives can overcome the shortcomings of LDHs. As great progress has been made in this field so far, we believe that a timely review is warranted. Thus, in this contribution, the synergistic effect of LDHs with other flame retardant additives including (1) phosphorus-containing compounds, (2) graphene and carbon compounds, (3) intumescent flame retardants, (4) magnesium hydroxide, (5) borate-containing compounds, and (6) some other flame retardant compounds will be critically reviewed. For each type of additive, the synergistic mechanism with LDHs, and their performance on both flame retardancy and thermal stability will be discussed. We believe that this work will inspire and guide researchers from a wide range of backgrounds and help to pave the way for major breakthroughs in both fundamental studies and industrial applications in this field.
RESUMO
Liver sinusoidal endothelial cells (LSECs) have great capacity for liver regeneration, and this capacity can easily switch to profibrotic phenotype, which is still poorly understood. In this study, we elucidated a potential target in LSECs for regenerative treatment that can bypass fibrosis during chronic liver injury. Proregenerative LSECs can be transformed to profibrotic phenotype after 4 weeks of carbon tetrachloride administration or 10 days of bile duct ligation. This phenotypic alternation of LSECs was mediated by extracellular regulated protein kinases 1 and 2 (Erk1/2)-Akt axis switch in LSECs during chronic liver injury; Erk1/2 was normally associated with maintenance of the LSEC proregenerative phenotype, inhibiting hepatic stellate cell (HSC) activation and promoting tissue repair by enhancing nitric oxide (NO)/reactive oxygen species (ROS) ratio and increasing expression of hepatic growth factor (HGF) and Wingless-type MMTV integration site family member 2 (Wnt2). Alternatively, Akt induced LSEC profibrotic phenotype, which mainly stimulated HSC activation and concomitant senescence by reducing NO/ROS ratio and decreasing HGF/Wnt2 expression. LSEC-targeted adenovirus or drug particle to promote Erk1/2 activity can alleviate liver fibrosis, accelerate fibrosis resolution, and enhance liver regeneration. This study demonstrated that the Erk1/2-Akt axis acted as a switch to regulate the proregenerative and profibrotic phenotypes of LSECs, and targeted therapy promoted liver regeneration while bypassing fibrosis, providing clues for a more effective treatment of liver diseases.
Assuntos
Hepatopatias/metabolismo , Hepatopatias/patologia , Regeneração Hepática , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Doença Crônica , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Imunofluorescência , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatias/etiologia , Hepatopatias/terapia , Camundongos , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Drug-disease associations provide important information for the drug discovery. Wet experiments that identify drug-disease associations are time-consuming and expensive. However, many drug-disease associations are still unobserved or unknown. The development of computational methods for predicting unobserved drug-disease associations is an important and urgent task. RESULTS: In this paper, we proposed a similarity constrained matrix factorization method for the drug-disease association prediction (SCMFDD), which makes use of known drug-disease associations, drug features and disease semantic information. SCMFDD projects the drug-disease association relationship into two low-rank spaces, which uncover latent features for drugs and diseases, and then introduces drug feature-based similarities and disease semantic similarity as constraints for drugs and diseases in low-rank spaces. Different from the classic matrix factorization technique, SCMFDD takes the biological context of the problem into account. In computational experiments, the proposed method can produce high-accuracy performances on benchmark datasets, and outperform existing state-of-the-art prediction methods when evaluated by five-fold cross validation and independent testing. CONCLUSION: We developed a user-friendly web server by using known associations collected from the CTD database, available at http://www.bioinfotech.cn/SCMFDD/ . The case studies show that the server can find out novel associations, which are not included in the CTD database.
Assuntos
Biologia Computacional/métodos , Doença , Descoberta de Drogas , Modelos Teóricos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Projetos de Pesquisa , HumanosRESUMO
Alternative splicing (AS) generates multiple isoforms from a single precursor mRNA, and these isoforms usually exhibit different tissue distributions and functions. Aberrant protein isoforms can lead to abnormalities in protein function and may even result in genetic disorders or cancer. In recent years, splice-switching oligonucleotides (SSOs) have emerged as a promising therapeutic strategy for several neurological diseases, but the efficacy of this strategy in other organs is less reported. In this study, we designed and synthesized SSOs targeting the splicing regulators of exon 12 of the Tak1 gene, inducing variant switching between Tak1-A and Tak1-B. We also designed SSOs capable of knockdown both Tak1 variants by inducing the aberrant splicing of exon 4. The Vivo-morpholino SSOs showed significant splice-switching of Tak1 in mouse liver, with a persistence of at least 10 days after initial SSOs delivery. Bioinformatics analysis indicated a lipid metabolism-related function for Tak1-B but not Tak1-A. The conversion of Tak1-B to Tak1-A consistently led to significant accumulation of lipids in cultured AML12â¯cells, as well as the dysregulation of several lipid metabolism-related genes in mouse liver. Different functional properties of the two isoforms may explain the conflicting functions previously reported for Tak1. In conclusion, our research clarified the different functions of Tak1 isoforms, and provided an efficient strategy for the functional research of the AS isoforms.
Assuntos
Processamento Alternativo , Fígado/metabolismo , MAP Quinase Quinase Quinases/genética , Oligonucleotídeos/genética , Animais , Células Cultivadas , Biologia Computacional , Metabolismo dos Lipídeos/genética , Camundongos , Oligonucleotídeos/síntese química , Oligonucleotídeos/farmacologia , Isoformas de Proteínas/fisiologiaRESUMO
Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcription diversity. However, the functional roles of AS in multiple cell types from one organ have not been reported. Here, we provide the most comprehensive profile for cell-type-resolved AS patterns in mouse liver. A total of 13,637 AS events are detected, representing 81.5% of all known AS events in the database. About 46.2% of multi-exon genes undergo AS from the four cell types of mouse liver: hepatocyte, liver sinusoidal endothelial cell, Kupffer cell and hepatic stellate cell, which regulates cell-specific functions and maintains cell characteristics. We also present a cell-type-specific splicing factors network in these four cell types of mouse liver, allowing data mining and generating knowledge to elucidate the roles of splicing factors in sustaining the cell-type-specialized AS profiles and functions. The splicing switching of Tak1 gene between different cell types is firstly discovered and the specific Tak1 isoform regulates hepatic cell-type-specific functions is verified. Thus, our work constructs a hepatic cell-specific splicing landscape and reveals the considerable contribution of AS to the cell type constitution and organ features.
RESUMO
We found in our previous study that layered double hydroxides (LDHs) which undergo aqueous miscible organic solvent treatment (AMOST) can tune the hydrophobicity surface of LDHs to be hydrophobic, and then the solvent mixing method can be used to prepare polymer/LDH nanocomposites. However, flame retardant property is not very high if LDHs are only used. In this present work, ammonium polyphosphate (APP) intercalated LDHs and zinc borate (ZB) was incorporated into a polypropylene (PP) matrix using the solvent mixing method. The structures, morphologies, and performance of the composites were characterized carefully. The peak heat release rate (PHRR) reduction of PP containing 10 and 20 wt % APP-LDH reached 27% and 55%, respectively, which increased up to 63% compared with PP/CO3-LDH. After incorporating 2 wt % ZB in the PP/APP-LDH system, the flame retardant property was further improved. Polypropylene composites with 20 wt % APP-LDH and 2 wt % ZB showed a 58% PHRR reduction. In addition, thermogravimetric analyzer (TGA) results indicated that the addition of APP-LDH and ZB improved the temperature at 50% weight loss (T50%) and the char formation of the materials significantly.
RESUMO
Mass-spectrometry-based phosphoproteomic workflows traditionally require efficient prefractionation and enrichment of phosphopeptides to gain an in-depth, global, and unbiased systematic investigation of phosphoproteome. Here we present TiO2 with tandem fractionation (TAFT) approach, which combines titanium dioxide (TiO2) enrichment and tandem high-pH reverse-phase (HpRP) for phosphoproteome analysis in a high-throughput manner; the entire workflow takes only 3 h to complete without laborious phosphopeptide preparation. We applied this approach to HeLa and HepG2.2.15 cells to characterize the capability of TAFT approach, which enables deep identification and quantification of more than 14â¯000 unique phosphopeptides in a single sample from 1 mg of protein as starting materials in <4 h of MS measurement. In total, we identified and quantified 21â¯281 phosphosites in two cell lines with >91% selectivity and high quantitative reproducibility (average Pearson correlation is 0.90 between biological replicates). More generally, the presented approach enables rapid, deep, and reproducible phosphoproteome analysis in a high-throughput manner with low cost, which should facilitate our understanding of signaling networks in a wide range of biological systems or the process of clinical applications.
Assuntos
Fosfopeptídeos/análise , Proteômica/métodos , Titânio , Células HeLa , Células Hep G2 , Humanos , Reprodutibilidade dos Testes , Transdução de Sinais , Fatores de TempoRESUMO
Sinusoidal dedifferentiation is a complicated process induced by several factors, and exists in early stage of diverse liver diseases. The mechanism of sinusoidal dedifferentiation is poorly unknown. In this study, we established a NaAsO2-induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial cells were isolated and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic approach was adopted to globally examine the effects of arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of sinusoidal dedifferentiation. In all, 4205 proteins were identified and quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were significantly changed in NaAsO2 group, compared with the normal control. Validation by western blot showed increased level of clathrin-associated sorting protein Disabled 2 (Dab2) in NaAsO2 group, indicating that it may regulate receptor endocytosis, which served as a mechanism to augment intracellular VEGF signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and angiogenesis.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Desdiferenciação Celular , Endocitose , Células Endoteliais/citologia , Células Endoteliais/fisiologia , Fígado/citologia , Proteômica , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Proteínas Reguladoras de Apoptose , Desdiferenciação Celular/efeitos dos fármacos , Separação Celular , Biologia Computacional/métodos , Células Endoteliais/efeitos dos fármacos , Separação Imunomagnética , Masculino , Camundongos , Proteoma , Proteômica/métodos , Receptores de Superfície Celular/metabolismo , Reprodutibilidade dos TestesRESUMO
New tools are needed to enable rapid detection, identification, and reporting of infectious viral and microbial pathogens in a wide variety of point-of-care applications that impact human and animal health. We report the design, construction, and characterization of a platform for multiplexed analysis of disease-specific DNA sequences that utilizes a smartphone camera as the sensor in conjunction with a hand-held "cradle" that interfaces the phone with a silicon-based microfluidic chip embedded within a credit-card-sized cartridge. Utilizing specific nucleic acid sequences for four equine respiratory pathogens as representative examples, we demonstrated the ability of the system to utilize a single 15 µL droplet of test sample to perform selective positive/negative determination of target sequences, including integrated experimental controls, in approximately 30 min. Our approach utilizes loop-mediated isothermal amplification (LAMP) reagents predeposited into distinct lanes of the microfluidic chip, which when exposed to target nucleic acid sequences from the test sample, generates fluorescent products that when excited by appropriately selected light emitting diodes (LEDs), are visualized and automatically analyzed by a software application running on the smartphone microprocessor. The system achieves detection limits comparable to those obtained by laboratory-based methods and instruments. Assay information is combined with the information from the cartridge and the patient to populate a cloud-based database for epidemiological reporting of test results.