RESUMEN
Proliferative vitreoretinopathy (PVR) is a complex disease that significantly contributes to recurrent retinal detachment. Its development is notably affected by epithelial-mesenchymal transition (EMT), where apoptosis plays a crucial role as a regulator of EMT. However, the function of MeCP2 in governing apoptosis and EMT in retinal pigment epithelial (RPE) cells and its implications for PVR development have remained inadequately understood. Thus, we investigated the impact of MeCP2 on proliferation, migration, apoptosis and EMT in ARPE-19 cells to provide a fresh perspective on the etiology of PVR. The morphological changes in ARPE-19 cells induced by recombinant human MeCP2 protein and MeCP2 knockdown were observed. Wound healing assay were performed to verify the effects of recombinant human MeCP2 protein and MeCP2 knockdown on ARPE-19 cell migration. Furthermore, cell proliferation was assessed using the CCK-8 assay and flow cytometry. Western blot analysis, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and immunofluorescence analysis were conducted to measure the protein levels associated with apoptosis, cell cycle and EMT. Western blot analysis and immunofluorescence assays confirmed that MeCP2 promoted EMT formation in ARPE-19 cells. The CCK-8 assay revealed that MeCP2 treatment enhanced the proliferation of ARPE-19 cells, whereas MeCP2 knockdown inhibited ARPE-19 cell proliferation. Treatment with recombinant human MeCP2 protein and MeCP2 knockdown altered the morphology of ARPE-19 cells. Wound healing assay demonstrated that MeCP2 knockdown inhibited ARPE-19 cell migration, and MeCP2 treatment promoted ARPE-19 cell migration. MeCP2 knockdown induced a G0/G1 phase block, inhibiting cell growth, and qRT-PCR data indicated reduced expression of cell cycle-related genes. Increased apoptosis was observed after MeCP2 knockdown in ARPE-19 cells. Overall, MeCP2 treatment stimulates cell proliferation, migration and EMT formation; conversely, MeCP2 knockdown inhibits EMT, cell proliferation, migration and cell cycle G1/S phase transition, and induces apoptosis.
RESUMEN
Reducing iridium (Ir) catalyst loading for acidic oxygen evolution reaction (OER) is a critical strategy for large-scale hydrogen production via proton exchange membrane (PEM) water electrolysis. However, simultaneously achieving high activity, long-term stability, and reduced material cost remains challenging. To address this challenge, we develop a framework by combining density functional theory (DFT) prediction using model surfaces and proof-of-concept experimental verification using thin films and nanoparticles. DFT results predict that oxidized Ir monolayers over titanium nitride (IrOx/TiN) should display higher OER activity than IrOx while reducing Ir loading. This prediction is verified by depositing Ir monolayers over TiN thin films via physical vapor deposition. The promising thin film results are then extended to commercially viable powder IrOx/TiN catalysts, which demonstrate a lower overpotential and higher mass activity than commercial IrO2 and long-term stability of 250 h to maintain a current density of 10 mA cm-2. The superior OER performance of IrOx/TiN is further confirmed using a proton exchange membrane water electrolyzer (PEMWE), which shows a lower cell voltage than commercial IrO2 to achieve a current density of 1 A cm-2. Both DFT and in situ X-ray absorption spectroscopy reveal that the high OER performance of IrOx/TiN strongly depends on the IrOx-TiN interaction via direct Ir-Ti bonding. This study highlights the importance of close interaction between theoretical prediction based on mechanistic understanding and experimental verification based on thin film model catalysts to facilitate the development of more practical powder IrOx/TiN catalysts with high activity and stability for acidic OER.
RESUMEN
In traditional Chinese medicine, Lycium barbarum is of rich medicinal value, and its polysaccharides are particularly interesting due to their significant pharmacological effects and potential health benefits. This study investigated the immunomodulatory effects of Lycium barbarum polysaccharides (LBPs) by examining their interaction with the TLR4/MD-2 complex and the impacts of gastrointestinal digestion on these interactions. We discovered that the affinity binding of LBPs for TLR4/MD-2 and their cytokine induction capability are influenced by molecular weight, with medium-sized LBPs (100-300 kDa) exhibiting stronger binding affinity and induction capability. Conversely, LBPs smaller than 10 kDa showed reduced activity. Additionally, the content of arabinose and galactose within the LBPs fractions was found to correlate positively with both receptor affinity and cytokine secretion. Simulated gastrointestinal digestion resulted in the degradation of LBPs into smaller fragments that are rich in glucose. Although these fragments exhibited decreased binding affinity to the TLR4/MD-2 complex, they maintained their activity to promote cytokine production. Our findings highlight the significance of molecular weight and specific monosaccharide composition in the immunomodulatory function of LBPs and emphasize the influence of gastrointestinal digestion on the effects of LBPs. This research contributes to a better understanding of the mechanisms underlying the immunomodulatory effects of traditional Chinese medicine polysaccharides and their practical application.
Asunto(s)
Digestión , Medicamentos Herbarios Chinos , Peso Molecular , Receptor Toll-Like 4 , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Receptor Toll-Like 4/metabolismo , Digestión/efectos de los fármacos , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Humanos , Citocinas/metabolismo , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/efectos de los fármacos , Animales , Lycium/química , Ratones , Monosacáridos/análisis , Monosacáridos/química , Polisacáridos/farmacología , Polisacáridos/químicaRESUMEN
OBJECTIVES: This study evaluated the expression and significance of SNHG3 in Rheumatoid arthritis (RA) aiming to explore a biomarker and regulator for RA. METHODS: The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using PCR. The RA animal models were induced by the porcine type II collagen with Wistar rats and validated by the foot volume and AI score. The human fibroblast-like synoviocytes (H-FLS) were treated with LPS to mimic the injury during RA onset and the cell growth was assessed by CCK8 assay. RESULTS: SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine type II collagen induced increasing foot volume and AI scores of rats and SNHG3 was downregulated in RA rats. In LPS-induced H-FLS, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation. CONCLUSIONS: Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress via negatively modulating miR-128-3p.
RESUMEN
Cost-effective transition metal chalcogenides are highly promising electrocatalysts for both alkaline and acidic hydrogen evolution reactions (HER). However, unsatisfactory HER kinetics and stability have severely hindered their applications in industrial water electrolysis. Herein, a nanoflowers-shaped W-doped cubic/orthorhombic phase-mixed CoSe2 catalyst ((c/o)-CoSe2-W) is reported. The W doping induces spontaneous phase transition from stable phase cubic CoSe2 (c-CoSe2) to metastable phase orthorhombic CoSe2, which not only enables precise regulation of the ratio of two phases but also realizes W doping at the interfaces of two phases. The (c/o)-CoSe2-W catalyst exhibits a Pt-like HER activity in both alkaline and acidic media, with record-low HER overpotentials of 29.8 mV (alkaline) and 35.9 mV (acidic) at 10 mA cm-2, respectively, surpassing the vast majority of previously reported non-precious metal electrocatalysts for both alkaline and acidic HER. The Pt-like HER activities originate from the formation of Co-Se-W active species on the c-CoSe2 side at the phase interface, which effectively modulates electron structures of active sites, not only enhancing H2O adsorption and dissociation at Co sites but also optimizing H* adsorption to ΔGH* ≈ 0 at W sites. Benefiting from the abundant phase interfaces, the catalyst also displays outstanding long-term durability in both acidic and alkaline media.
RESUMEN
Background: Malignant atrophic papulosis (MAP) is a rare obliterative vasculopathy whose etiology and pathophysiological mechanisms remain unknown, and the treatment is still empirical. It can involve multiple systems, especially the gastrointestinal tract and central nervous system, and has a poor prognosis. Case presentation: A 20-year-old Chinese male appeared to have Widespread atrophic papules and plaques, intermittent abdominal pain, recurrent bowel perforation, and psoas abscess. The clinical diagnosis of MAP was supported by skin biopsy. He was then treated with anticoagulants, antiplatelets, glucocorticoids, and immunosuppressants and started on eculizumab and hirudin after the first surgical interventions. Despite the aggressive immunosuppression, anticoagulant, antiplatelet, humanized monoclonal antibodies, and surgery therapy, he died five months after presentation. Conclusions: MAP is an extremely rare obliterative vasculopathy manifesting as benign cutaneous involvement or potentially malignant systemic involvement. MAP patients who exhibit any abdominal symptoms should undergo laparoscopy and evaluation in time and start on eculizumab and treprostinil as soon as possible, as the combination of them is presently the most effective treatment option for gastrointestinal MAP and hopefully reduce mortality.
RESUMEN
ß-Cyclodextrin (ß-CD) and its derivatives have been widely employed in the field of chiral separation, but they are still faced the limitation of low enantioselectivity and complex processes. Derivatization with functional molecules or preparation as bridging dimers are the two main modifications for ß-CD to obtain chiral recognition compounds. Herein, a partially derived bridged ß-CD (CPI-EBCD) bonded chiral stationary phases was prepared to improve enantioseparation. The chiral recognition moiety was synthesized by a bridged ß-cyclodextrin dimer using a short-chain bridging agent (ethylenediamine) and then modifying the bridged cyclodextrin with a 4-chlorophenylisocyanate (CPI) containing a benzene ring and polar group. Compared with natural ß-CD, dual-chambered CPI-EBCDs have better encapsulation synergies and more recognition sites with the guest molecule, while the short flexible bridging groups make the double cavities closer and more easily recognizable as linear molecules. The introduction of derived groups CPI provided more recognition sites and more types of interactions, including π-π interaction force, hydrogen bonding effect, and dipole-dipole interaction, thus improving the enantiomer-specific chirality recognition effect. The chiral stationary phase CPI-EBCDP was obtained by connecting CPI-EDCB with mesoporous silica microspheres by simple photochemical reaction using a green non-toxic diazo resin as coupling agent, simplifying preparation process. In the reversed phase mode of liquid chromatography, CPI-EBCDP has excellent chiral recognition ability, and 12 chiral compounds are successfully isolated by optimizing mobile phase conditions, with good reproducibility and stability. The successful preparation of this new chiral stationary phase provides an important reference for the subsequent development of cyclodextrin-like chiral stationary phases.
RESUMEN
N6-methyladenosine (m6A) is a major type of RNA modification implicated in various pathophysiological processes. Transforming growth factor ß2 (TGF-ß2) induces epithelial-mesenchymal transition (EMT) in retinal pigmental epithelial (RPE) cells and promotes the progression of proliferative vitreoretinopathy (PVR). However, the role of m6A methylation in the EMT of human telomerase reverse transcriptase (hTERT) retinal pigmental epithelium (RPE)-1 cells has not been clarified. Here, we extracted RNA from RPE cells subjected to 0 or 20 ng/mL TGF-ß2 for 72 h and identified differentially methylated genes (DMGs) by m6A-Seq and differentially expressed genes (DEGs) by RNA-Seq. We selected the genes related to EMT by conjoint m6A-Seq/RNA-Seq analysis and verified them by qRT-PCR. We then confirmed the function of m6A methylation in the EMT of RPE cells by knocking down the methyltransferase METTL3 and the m6A reading protein YTHDF1. Sequencing yielded 5814 DMGs and 1607 DEGs. Conjoint analysis selected 467 genes altered at the m6A and RNA levels that are closely associated with the EMT-related TGF-ß, AGE-RAGE, PI3K-Akt, P53, and Wnt signaling pathways. We also identified ten core EMT genes ACTG2, BMP6, CDH2, LOXL2, SNAIL1, SPARC, BMP4, EMP3, FOXM1, and MYC. Their RNA levels were evaluated by qRT-PCR and were consistent with the sequencing results. We observed that METTL3 knockdown enhanced RPE cell migration and significantly upregulated the EMT markers N-cadherin (encoded by CDH2), fibronectin (FN), Snail family transcription repressor (SLUG), and vimentin. However, YTHDF1 knockdown had the opposite effects and decreased both cell migration and the N-cadherin, FN, and SLUG expression levels. The present study clarified TGF-ß2-induced m6A- and RNA-level differences in RPE cells, indicated that m6A methylation might regulate EMT marker expression, and showed that m6A could regulate TGF-ß2-induced EMT.
Asunto(s)
Adenina/análogos & derivados , Factor de Crecimiento Transformador beta2 , Vitreorretinopatía Proliferativa , Humanos , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/farmacología , Factor de Crecimiento Transformador beta2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Vitreorretinopatía Proliferativa/genética , Vitreorretinopatía Proliferativa/metabolismo , Transición Epitelial-Mesenquimal , Metilación , Cadherinas/genética , Cadherinas/metabolismo , ARN/genética , ARN/metabolismo , Metiltransferasas/metabolismo , Glicoproteínas de Membrana/metabolismoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. METHODS: Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. RESULTS: NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. CONCLUSIONS: There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.
Asunto(s)
Artritis Reumatoide , MicroARNs , ARN Largo no Codificante , Humanos , Artritis Reumatoide/diagnóstico , Relevancia Clínica , Interleucina-6 , Factor de Necrosis Tumoral alfaRESUMEN
Herein we present a novel linear supramolecular polymeric structure formed in both the solution and solid state, utilizing the host-guest recognition motif between perethylated pillar[5]arene and tetrathiafulvalene.
RESUMEN
Viral respiratory infections are major human health concerns. The most striking epidemic disease, COVID-19 is still on going with the emergence of fast mutations and drug resistance of pathogens. A few polysaccharide macromolecules from traditional Chinese medicine (TCM) have been found to have direct anti-SARS-CoV-2 activity but the mechanism remains unclear. In this study, we evaluated the entry inhibition effect of Lycium barbarum polysaccharides (LBP) in vitro and in vivo. We found LBP effectively suppressed multiple SARS-CoV-2 variants entry and protected K18-hACE2 mice from invasion with Omicron pseudovirus (PsV). Moreover, we found LBP interfered with early entry events during infection in time-of-addition (TOA) assay and SEM observation. Further surface plasmon resonance (SPR) study revealed the dual binding of LBP with Spike protein and ACE2, which resulted in the disruption of Spike-ACE2 interaction and subsequently triggered membrane fusion. Therefore, LBP may act as broad-spectrum inhibitors of virus entry and nasal mucosal protective agent against newly emerging respiratory viruses, especially SARS-CoV-2.
Asunto(s)
COVID-19 , Lycium , Humanos , Animales , Ratones , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2 , Glicoproteína de la Espiga del Coronavirus , Unión ProteicaRESUMEN
The development of Pt-based catalysts for use in fuel cells that meet performance targets of high activity, maximized stability, and low cost remains a huge challenge. Herein, we report a nitrogen (N)-doped high-entropy alloy (HEA) electrocatalyst that consists of a Pt-rich shell and a N-doped PtCoFeNiCu core on a carbon support (denoted as N-Pt/HEA/C). The N-Pt/HEA/C catalyst showed a high mass activity of 1.34 A mgPt-1 at 0.9 V for the oxygen reduction reaction (ORR) in rotating disk electrode (RDE) testing, which substantially outperformed commercial Pt/C and most of the other binary/ternary Pt-based catalysts. The N-Pt/HEA/C catalyst also demonstrated excellent stability in both RDE and membrane electrode assembly (MEA) testing. Using operando X-ray absorption spectroscopy (XAS) measurements and theoretical calculations, we revealed that the enhanced ORR activity of N-Pt/HEA/C originated from the optimized adsorption energy of intermediates, resulting in the tailored electronic structure formed upon N-doping. Furthermore, we showed that the multiple metal-nitrogen bonds formed synergistically improved the corrosion resistance of the 3d transition metals and enhanced the ORR durability.
RESUMEN
Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.
RESUMEN
MeCP2 is a transcriptional regulator that is involved in epithelial-mesenchymal transition (EMT) and is highly expressed in proliferative vitreoretinopathy. m6A methylation is a critical post-transcriptional regulation in eukaryotic cells. However, the connection between MeCP2 and m6A methylation has not been revealed in retinal pigment epithelium (RPE), and the regulatory role of MeCP2 at the post-transcriptional level in an m6A-dependent manner is rarely investigated. In this study, we used sequencing to reveal differences in transcript levels and m6A abundance of individual genes in RPE cells after treatment with human recombinant protein MeCP2. The biological functions and processes of differential genes were further analyzed by bioinformatics. The results exhibited that after MeCP2 treatment, 65 genes were up-regulated and 43 genes were down-regulated at the transcription level, and 4 peaks were hypermethylated and 9,041 peaks were hypomethylated at the m6A modification level. Enrichment analysis found that differentially expressed genes were associated with organic acid metabolism, melanogenesis, and vascular smooth muscle contraction. In addition, differentially methylated genes were related to cell junction, RNA processing and metabolism, cell activity, actin cytoskeleton, and several signaling pathways associated with EMT. Further conjoint analysis indicated that the transcription and m6A levels of the EGR1, ELOVL2, and SFR1 genes were altered, and EGR1 is an essential transcription factor in the EMT process. The RNA levels and m6A levels of the three genes were verified by qPCR and m6A-IP-qPCR, respectively. Overall, this study preliminarily revealed the differential mapping of MeCP2-induced m6A modifications, which contributes to the study of the epigenetic and EMT mechanism in RPE cells.
RESUMEN
The spliceosome, a large complex containing five conserved small ribonucleoprotein particles (snRNPs) U1, U2, U4, U5 and U6, plays important roles in precursor messenger RNA splicing. However, the function and mechanism of the spliceosomal snRNPs have not been thoroughly studied in the pathogenic yeast Cryptococcus deneoformans. In this study, we identified a U2A' homologous protein as a component of the cryptococcal U2 snRNP, which was encoded by the LEA1 gene. Using the "suicide" CRISPR-Cas9 tool, we deleted the LEA1 gene in C. deneoformans JEC21 strain and obtained the disruption mutant lea1Δ. The mutant showed a hypersensitivity to 0.03 % sodium dodecyl sulfate, as well as disordered chitin distribution in cell wall observed with Calcofluor White staining, which collectively illustrated the function of U2A' in maintenance of cell wall integrity. Further examination showed that lea1Δ displayed a decreased tolerance to lower or elevated temperatures, osmotic pressure and oxidative stress. The lea1Δ still exhibited susceptibility to geneticin and 5-flucytosine, and increased resistance to ketoconazole. Even, the mutant had a reduced capsule, and the virulence of lea1Δ in the Galleria mellonella model was decreased. Our results indicate that the U2A'-mediated RNA-processing has a particular role in the processing of gene products involved in response to stresses and virulence.
RESUMEN
Fluorescent supramolecular polymers have garnered significant attention due to their successful integration of supramolecular polymers and fluorescence, offering vast potential for applications in sensing, imaging, optoelectronics, and photonics. In this study, we present a novel supramolecular polymer based on P5-OH, derived from mono-substituted pillararene macrocycles. Notably, these formed supramolecular polymeric aggregates exhibit a prominent blue emission, representing a rare instance of fluorescent polymers devoid of conventional chromophores. Furthermore, through the modification of alkyl chain ending groups attached to pillar[5]arenes, slight shifts in the emission peak could be observed. This research expands the scope of functional supramolecular polymeric systems utilizing pillararenes, providing valuable insights for the design of innovative luminescent materials and optical devices.
RESUMEN
Cytonuclear disruption may accompany allopolyploid evolution as a consequence of the merger of different nuclear genomes in a cellular environment having only one set of progenitor organellar genomes. One path to reconcile potential cytonuclear mismatch is biased expression for maternal gene duplicates (homoeologs) encoding proteins that target to plastids and/or mitochondria. Assessment of this transcriptional form of cytonuclear coevolution at the level of individual cells or cell types remains unexplored. Using single-cell (sc-) and single-nucleus (sn-) RNAseq data from eight tissues in three allopolyploid species, we characterized cell type-specific variations of cytonuclear coevolutionary homoeologous expression and demonstrated the temporal dynamics of expression patterns across development stages during cotton fiber development. Our results provide unique insights into transcriptional cytonuclear coevolution in plant allopolyploids at the single-cell level.
Asunto(s)
Mitocondrias , Plastidios , Mitocondrias/genética , Diferenciación Celular , Núcleo SolitarioRESUMEN
Peony seed meal (PSM) is the by-product obtained from peony seeds after oil extraction. In this study, PSM was incorporated into traditional koji-making, and its impacts on koji enzyme activities and flavor compounds in final products were investigated. In the process of koji fermentation, the optimal addition ratio of PSM to soybean was determined as 7:3. Under this ratio, the maximum enzyme activities of neutral protease, amylase, and glucoamylase were 1177.85, 686.58, and 1564.36 U/g, respectively, and the koji obtained was subjected to maturation. During post-fermentation, changes in the fermentation characteristics of the paste samples were monitored, and it was found that compared to the soybean paste without PSM, the enzyme activities maintained at a relatively good level. The PSM soybean paste contained a total of 80 flavor compounds and 11 key flavor compounds (OAV ≥ 1), including ethyl isovalerate, isovaleric acid, hexanal, phenylacetaldehyde, 3-Methyl-1-butanol 4-heptanone, 2-pentylfuran, methanethiol ester caproate, isoamyl acetate, 3-methyl-4-heptanone, and isovaleraldehyde. These findings could be used to improve the quality of traditional fermented paste, enrich its flavor, and simultaneously promote PSM as a valuable resource for fermented foods.
RESUMEN
BACKGROUND: N6-methyladenosine (m6A) participates in diverse physiological processes and contributes to many pathological conditions. Epithelial-mesenchymal transition (EMT) of retinal pigmental epithelial (RPE) cells plays an essential role in retinal-related diseases, and transforming growth factor ß2 (TGF-ß2) is known to induce EMT in vitro. However, the effect of TGF-ß2 on m6A methylation in RPE cells is not yet known. METHODS: RNA-seq and MeRIP-seq were performed to analyze changes at the mRNA and m6A levels after TGF-ß2 treatment of human ARPE-19 cells. mRNA levels and total m6A levels were subsequently validated. RESULTS: Sequencing revealed 929 differentially expressed genes and 7328 differentially methylated genes after TGF-ß2 treatment. Conjoint analysis identified 290 genes related to microtubule cytoskeleton, focal adhesion, ECM-receptor interaction, cell division, cell cycle, AGE-RAGE, PI3K-Akt and cGMP-PKG pathways. Further analysis revealed that 12 EMT-related genes were altered at the mRNA and m6A levels after TGF-ß2 treatment (CALD1, CDH2, FN1, MMP2, SPARC, KRT7, CLDN3, ELF3, FGF1, LOXL2, SHROOM3 and TGFBI). Moreover, the total m6A level was also reduced. CONCLUSIONS: This study revealed the transcriptional profiling of m6A modification induced by TGF-ß2 in RPE cells. Novel connections were discovered between m6A modification and TGF-ß2-induced EMT, suggesting that m6A may play crucial roles in the EMT process.
Asunto(s)
Adenosina , Transición Epitelial-Mesenquimal , Epitelio Pigmentado de la Retina , Factor de Crecimiento Transformador beta2 , Humanos , Factor de Crecimiento Transformador beta2/farmacología , Epitelio Pigmentado de la Retina/citología , Línea Celular , RNA-Seq , Metilación , Adenosina/análogos & derivadosRESUMEN
Efficient C-C bond cleavage and oxidation of alcohols to CO2 is the key to developing highly efficient alcohol fuel cells for renewable energy applications. In this work, we report the synthesis of core/shell Au/Pt nanowires (NWs) with stepped Pt clusters deposited along the ultrathin (2.3 nm) stepped Au NWs as an active catalyst to effectively oxidize alcohols to CO2. The catalytic oxidation reaction is dependent on the Au/Pt ratios, and the Au1.0/Pt0.2 NWs have the largest percentage (â¼75%) of stepped Au/Pt sites and show the highest activity for ethanol electro-oxidation, reaching an unprecedented 196.9 A/mgPt (32.5 A/mgPt+Au). This NW catalyst is also active in catalyzing the oxidation of other primary alcohols, such as methanol, n-propanol, and ethylene glycol. In situ X-ray absorption spectroscopy and infrared spectroscopy are used to characterize the catalyst structure and to identify key reaction intermediates, providing concrete evidence that the synergy between the low-coordinated Pt sites and the stepped Au NWs is essential to catalyze the alcohol oxidation reaction, which is further supported by DFT calculations that the C-C bond cleavage is indeed enhanced on the undercoordinated Pt-Au surface. Our study provides important evidence that a core/shell structure with stepped core/shell sites is essential to enhance electrochemical oxidation of alcohols and will also be central to understanding electro-oxidation reactions and to the future development of highly efficient direct alcohol fuel cells for renewable energy applications.