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1.
Signal Transduct Target Ther ; 9(1): 159, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38937432

RESUMEN

The ORF9b protein, derived from the nucleocapsid's open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host-virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.


Asunto(s)
COVID-19 , Proteínas Cullin , Proteínas HSP90 de Choque Térmico , SARS-CoV-2 , Ubiquitinación , Replicación Viral , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , COVID-19/virología , COVID-19/genética , COVID-19/metabolismo , COVID-19/inmunología , Ubiquitinación/genética , Células HEK293 , Benzoquinonas/farmacología , Estabilidad Proteica , Células Vero , Proteínas Virales/genética , Proteínas Virales/metabolismo , Lactamas Macrocíclicas
2.
Adv Sci (Weinh) ; 11(11): e2308513, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38225720

RESUMEN

A noncovalent organocatalytic concerted addition of phenol to glycal is developed for the stereoselective and regioselective construction of biologically important phenolic 2-deoxyglycosides, featuring wide substrate tolerance. The method relies on an anion-bridged dual hydrogen bond interaction which is experimentally proved by Nuclear Magnetic Resonance (NMR), Ultraviolet and visible (UV-vis), and fluorescence analysis. Experimental evidence including kinetic analysis, Kinetic Isotope Effect (KIE) studies, linear free energy relationship, Hammett plot, and density functional theory (DFT) calculations is provided for a concerted mechanism where a high-energy oxocarbenium ion is not formed. In addition, the potential utility of this method is further demonstrated by the synthesis of biologically active glycosylated flavones. The benchmarking studies demonstrate significant advances in this newly developed method compared to previous approaches.

3.
Rev Med Virol ; 34(1): e2500, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38126937

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.


Asunto(s)
COVID-19 , Receptores ErbB , Transducción de Señal , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Receptores ErbB/genética , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/uso terapéutico , Síndrome Post Agudo de COVID-19 , Fibrosis Pulmonar/metabolismo , SARS-CoV-2/metabolismo , Transducción de Señal/efectos de los fármacos
4.
Org Lett ; 25(40): 7327-7331, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37795817

RESUMEN

Herein, an electrochemical hydrogen atom transfer (HAT) strategy for C(sp2)-H formylation of electron-deficient quinolines and isoquinolines is described. The cheap methanol acts as a formyl source with a catalytic amount of N-hydroxyphthalimide (NHPI) as the hydrogen atom transfer (HAT) catalyst. The advantages of this reaction are transition-metal-catalyst- and chemical-oxidant-free conditions, and the protocol could also be applied to the direct C(sp2)-H acetylation or propionylation of quinolines.

5.
Curr Eye Res ; 48(11): 1034-1049, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37529844

RESUMEN

PURPOSE: To identify and validate the differentially expressed genes related to RNA methylation modification in diabetic retinopathy. METHODS: The data sets GSE12610 and GSE111465 related to diabetic retinopathy in the Gene Expression Omnibus were selected. The R software package was used to identify differentially expressed genes related to RNA methylation modification in diabetic retinopathy. Protein-protein interaction network was constructed to explore the interactions between proteins and predict proteins. Then, Gene Ontology annotation analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the potential enrichment pathways and clarify the biological functions of these genes. In addition, the correlation between them and immune cells was visualized, and receiver operating characteristic curves were drawn to evaluate the diagnostic performance of each one of them for diabetic retinopathy. To verify the differentially expressed genes, the mRNA expression of rat retinal vascular endothelial cells cultured in low and high glucose medium separately were detected by RT-qPCR. RESULTS: The expression of Lrpprc, Nsun4, Nsun6 and Trdmt1 were significantly up-regulated in diabetic retinopathy samples, while the expression of Cbll1, Hnrnpc, Mettl3 and Wtap were significantly down-regulated. Differentially expressed genes were mainly enriched in the RNA-methylation-medication pathways and biological function. The results of immune infiltration analysis proved that eosinophils aggregated more in diabetic group, while T cells follicular helper aggregated more in normal samples. These genes of Cbll1 (AUC = 0.986), Hnrnpc (AUC = 0.819), Lrpprc (AUC = 0.806), Mettl3 (AUC = 0.917), Nsun4 (AUC = 0.819), Nsun6 (AUC = 0.819), Trdmt1 (AUC = 0.972) and Wtap (AUC = 0.972) were respectively used as the diagnostic basis of diabetic retinopathy. According to the RT-qPCR results, the expression of Mettl3 was significantly down-regulated (p < 0.0005) in cells cultured in high glucose, while Trdmt1 (p < 0.05), Nsun4 (p < 0.05) and Nsun6 (p < 0.05) were significantly up-regulated. CONCLUSION: Differentially expressed genes such as Mettl3, Nsun4, Nsun6, and Trdmt1 should be conducted to explore, and the role of RNA methylation in the process of diabetic retinopathy would be revealed in-depth.

6.
ACS Omega ; 8(29): 26045-26054, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37521609

RESUMEN

For environmental catalysis, a central topic is the design of high-performance catalysts and advanced mechanism studies. In the case of the removal of flue gas pollutants from coal-fired power plants, highly selective nanoreactors have been widely utilized together with plasma discharge characteristics, such as the catalytic oxidation of NO. Herein, a novel reactor with a three-dimensional hollow structure of TiO2 confining Co3O4 nanoclusters (Co3O4/TiO2-3DHS) has been developed for plasma-catalytic oxidation of NO, whose performance was compared with that of the commercial TiO2 confining Co3O4 cluster (Co3O4/TiO2). Specifically, Co3O4/TiO2-3DHS presented a higher efficiency (almost 100%) within lower peak-peak voltage (VP-P). More importantly, the NO oxidation efficiency was between 91.5 and 94.5% after a long time of testing, indicating that Co3O4/TiO2-3DHS exhibits more robust sulfur and water tolerance. Density functional theory calculations revealed that such impressive performance originates from the unique cluster-support effect, which changes the distribution of the active sites on the catalyst surface, resulting in the selective adsorption of flue gas. This investigation provides a new strategy for constructing a three-dimensional hollow nanoreactor for the plasma-catalytic process.

7.
Carbohydr Polym ; 315: 121004, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37230641

RESUMEN

O-glycome is one of the important components of glycoconjugates in human milk which is speculated to provide protective features similar to those observed in free oligosaccharides. The effects of maternal secretor status on free oligosaccharides and N-glycome in milk have been well researched and documented. Currently, milk O-glycome of secretors (Se+) and nonsecretors (Se-) was investigated through reductive ß-elimination combined with porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry. A total of 70 presumptive O-glycan structures were identified, of which 25 O-glycans (including 14 sulfated O-glycans) were reported for the first time. Notably, 23 O-glycans exhibited significant differences between Se+ and Se- samples (p < 0.05). Compared to Se- group, the O-glycans of the Se+ group was two times more abundant in the total glycosylation, sialylation, fucosylation, and sulfation (p < 0.01). In conclusion, approximately one-third of the milk O-glycosylation was influenced by maternal FUT2-related secretor status. Our data will lay a foundation for the study of O-glycans structure-function relationship.


Asunto(s)
Leche Humana , Espectrometría de Masas en Tándem , Humanos , Leche Humana/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Polisacáridos/química , Oligosacáridos/química
8.
Carbohydr Polym ; 312: 120795, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37059535

RESUMEN

Glycosphingolipids (GSLs) in human milk regulate the immune system, support intestinal maturation, and prevent gut pathogens. The structural complexity and low abundance of GSLs limits their systematic analysis. Here, we coupled the use of monosialoganglioside 1-2-amino-N-(2-aminoethyl) benzamide (GM1-AEAB) derivatives as internal standards with HILIC-MS/MS to qualitatively and quantitatively compare GSLs in human, bovine, and goat milk. One neutral glycosphingolipid (GB) and 33 gangliosides were found in human milk, of which 22 were newly detected and three were fucosylated. Five GB and 26 gangliosides were identified in bovine milk, of which 21 were newly discovered. Four GB and 33 gangliosides were detected in goat milk, 23 of them newly reported. GM1 was the main GSL in human milk; whereas disialoganglioside 3 (GD3) and monosialogangloside 3 (GM3) were dominant in bovine and goat milk, respectively; N-acetylneuraminic acid (Neu5Ac) was detected in >88 % of GSLs in bovine and goat milk. N-hydroxyacetylneuraminic acid (Neu5Gc)-modified GSLs were 3.5 times more abundant in goat than in bovine milk; whereas GSLs modified with both Neu5Ac and Neu5Gc were 3 times more abundant in bovine than in goat milk. Given the health benefits of different GSLs, these results will facilitate the development of custom-designed human milk-based infant formula.


Asunto(s)
Glicoesfingolípidos , Espectrometría de Masas en Tándem , Humanos , Animales , Glicoesfingolípidos/química , Gangliósido G(M1)/análisis , Gangliósidos/análisis , Gangliósidos/química , Leche Humana/química , Cabras
9.
Mitochondrial DNA B Resour ; 8(2): 240-243, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36816060

RESUMEN

Bolbitis laxireticulata is a potential ornamental plant, which is restricted to eastern Asia. Here, we sequenced the complete chloroplast (cp) genome of B. laxireticulata and constructed a phylogenetic cp tree of Dryopteridaceae to study their relationships. The cp genome of B. laxireticulata is 153,093 bp in length, being made up of large single-copy (LSC, 83,169 bp), small single-copy (SSC, 21,538 bp), and a pair of region inverted repeats (IRs, 24,193 bp). It has 124 genes including 83 protein-coding genes, 33 tRNA genes, and eight rRNA genes. With the maximum-likelihood tree indicating, B. laxireticulata is more closely related to B. subcordata.

10.
Artículo en Inglés | MEDLINE | ID: mdl-36673669

RESUMEN

In China, due to the implementation of the Action Plan for Prevention and Control of Air Pollution (APPCAP), the concentrations of PM2.5 (fine particulate matter) and severe haze in most cities have decreased significantly. However, at present, haze pollution in China has not been completely mitigated, and the problem of O3 (ozone) has become prominent. Therefore, the prevention and control of haze and O3 pollution have become important and noticeable issues in the field of atmospheric management. We used the Baidu search indices of "haze" and "ozone" to reflect public concerns about air quality and uncover different correlations between level of concern and level of pollution, and then we identified regions in China that require public attention. The results showed that (1) over the last decade, the search index of haze had a rapid trend of variation in line with changes in haze pollution, but that of O3 had a relatively slowly increasing trend; (2) the lag days between the peaks of public concern and the peaks of air pollution became increasingly shorter according to daily data analysis; and (3) 96 polluted cities did not receive sufficient public attention. Although periods of heavily haze-polluted weather, which affects visibility, have generated much public concern, periods of slight pollution have not received enough public attention. Public health protection and environmental participation regarding these periods of slight pollution in China deserve appropriate levels of attention.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Ozono/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Contaminación del Aire/análisis , Material Particulado/análisis , China , Ciudades
11.
Mol Phylogenet Evol ; 178: 107633, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182051

RESUMEN

Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae, B. ser. Egenolfianae, and B. ser. Heteroclitae, are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America.


Asunto(s)
Dryopteridaceae , Helechos , Filogenia , Plastidios/genética , Secuencia de Bases
12.
J Bus Econ Stat ; 40(4): 1759-1771, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330150

RESUMEN

This article is concerned with causal mediation analysis with varying indirect and direct effects. We propose a varying coefficient mediation model, which can also be viewed as an extension of moderation analysis on a causal diagram. We develop a new estimation procedure for the direct and indirect effects based on B-splines. Under mild conditions, rates of convergence and asymptotic distributions of the resulting estimates are established. We further propose a F-type test for the direct effect. We conduct simulation study to examine the finite sample performance of the proposed methodology, and apply the new procedures for empirical analysis of behavioral economics data.

13.
J Virol ; 96(17): e0074122, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-35980206

RESUMEN

Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.


Asunto(s)
Infecciones por Coronavirus , Interacciones Microbiota-Huesped , Coronavirus del Síndrome Respiratorio de Oriente Medio , Proteolisis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteínas Virales , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Citocinas/inmunología , Humanos , Inmunidad Innata , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Terapia Molecular Dirigida , Complejo de la Endopetidasa Proteasomal/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismo , Proteínas Virales/química , Proteínas Virales/metabolismo , Replicación Viral
14.
Mol Cancer ; 21(1): 109, 2022 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524319

RESUMEN

BACKGROUND: Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. RESULTS: Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (ß-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. CONCLUSIONS: CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Circular/genética , ARN Interferente Pequeño , Regulación hacia Arriba
15.
Front Nutr ; 9: 790519, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35399670

RESUMEN

Food insecurity (FI) is a dynamic phenomenon, and its association with daily affect is unknown. We explored the association between daily FI and affect among low-income adults during a 2-seasonal-month period that covered days both pre- and during the COVID-19 pandemic. A total of 29 healthy low-income adults were recruited during fall in 2019 or 2020, 25 of whom were followed in winter in 2020 or 2021. Daily FI (measured once daily) and affect (measured 5 times daily) were collected over the 2nd-4th week in each month. Time-Varying-Effect-Models were used to estimate the association between daily FI and positive/negative affect (PA/NA). Overall, 902 person-days of daily-level data were collected. Daily FI was associated with lower PA in the 3rd and 4th week of fall and winter and with higher NA in the second half of winter months. Similar patterns of FI-affect relations were found pre- and during COVID-19 in the second half of a given month, while unique patterns of positive affect scores in the 2nd week and negative scores in the 1st week were only observed during COVID days. Our study supports a time-varying association between FI and affect in low-income adults. Future large studies are needed to verify the findings; ultimately, better understanding such associations may help identify, target, and intervene in food insecure adults to prevent adverse mental health outcomes.

16.
Comput Math Methods Med ; 2022: 9212116, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35295199

RESUMEN

Objective: DNA methylation played a vital role in the progression of diabetic retinopathy. In this study, we aimed to explore the role of DNA cytosine-5-methyltransferase 1 (DNMT1) in the development of early diabetic retinopathy and its potential underlying mechanism. Methods: Eight-week-old healthy Mongolian gerbils were used to establish type 1 diabetes using streptozotocin (STZ). Alteration of weight, fasting blood glucose, density of RGCs (Tuj1-labeled), and H&E-stained retinal cross sections were applied to evaluate the diabetic retinopathy mouse model. The global DNA methylation level of the retina at different time points after STZ injection was measured using the global methylation assay. Western blot was used to detect the protein expression of DNMT1, DNA methyltransferase 3A (DNMT3A), and 3B (DNMT3B). Quantitative reverse transcription-polymerase chain reactions (qRT-PCR) and western blot were used to determine the expression of CDKN2B. Cell proliferation and cell cycle were evaluated by the MTS assay and flow cytometry. Results: STZ injection caused the increased global DNA methylation level, which reached a maximum at 6 weeks after injection. Moreover, STZ injection caused the damage of RGCs. At 6 weeks after STZ injection, the expression levels of DNMT1 and DNMT3B were significantly increased in the STZ group. DNMT1-induced DNA hypermethylation inhibited the expression of CDKN2B (a negative regulator of cell cycle). DNMT1-mediated DNA methylation facilitated RGC proliferation via regulating the expression of CDKN2B. Conclusion: DNMT1-mediated DNA methylation played an important role in STZ-induced diabetic retinopathy via modulating CDKN2B expression.


Asunto(s)
Inhibidor p15 de las Quinasas Dependientes de la Ciclina/metabolismo , Retinopatía Diabética/metabolismo , Células Ganglionares de la Retina/metabolismo , Animales , Proliferación Celular , Biología Computacional , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/etiología , Retinopatía Diabética/patología , Técnicas de Silenciamiento del Gen , Gerbillinae , Masculino , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Estreptozocina/toxicidad
17.
Small ; 18(14): e2106680, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35199463

RESUMEN

Facilitating the mass transfer and spatial charge separation is a great challenge for achieving efficient oxidation of NO and outstanding sulfur resistance. Herein, a hydrothermal-assisted confinement growth technique is used to fabricate well-defined three-dimensional CuOx@MnOx hetero-shelled hollow-structure catalysts. By integrating the coupled plasma space reactor and the porous hierarchical structure of the catalyst, excellent stability (10 h) and high conversion of NO (93.86%) are reached under the concentration of SO2 (1000 mg m-3 ) and NO (200 mg m-3 ). Impressively, precise surface characterization and detailed density functional theory calculations show that the spatial hetero-shelled micro-reactor can orient the redox pairs transportation, facilitating the combination of NO with the surface coordinately unsaturated O atoms, and also prevent the poisoning of SO2 molecules due to the curvature and surface charge effect in the non-thermal plasma equipment.


Asunto(s)
Azufre , Catálisis , Oxidación-Reducción , Porosidad
18.
J Biol Chem ; 298(2): 101584, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35032548

RESUMEN

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.


Asunto(s)
Apoptosis , Infecciones por Coronavirus/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Proteínas no Estructurales Virales/metabolismo , Células A549 , Línea Celular , Biología Computacional , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Células Epiteliales/fisiología , Células Epiteliales/virología , Células HEK293 , Interacciones Huésped-Patógeno , Humanos
19.
J Phys Chem Lett ; 12(36): 8889-8896, 2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34498878

RESUMEN

Based on first-principles calculations, the ground state configuration (Cmma-CH) of a hydrogenated biphenylene sheet ( Science 2021, 372, 852) is carefully identified from hundreds of possible candidates generated by RG2 code ( Phys. Rev. B. 2018, 97, 014104). Cmma-CH contains four inequivalent benzene molecules in its crystalline cell due to its Cmma symmetry. Hydrogen atoms bond to carbon atoms in each benzene with a boat-like (DDUDDU) up/down sequence and reversed boat-1 (UUDUUD) sequence in adjacent benzene rings. Cmma-CH is energetically less stable than the proposed allotropes of hydrogenated graphene, but the formation energy for hydrogenating a biphenylene sheet is remarkably lower than that for hydrogenating graphene to graphane. Our results of mechanical and dynamical stability also confirm that Cmma-CH is a stable 2D hydrocarbon, which is expected to be realized experimentally. Especially, biphenylene undergoes a transition from normal metal to a wide band gap insulator (4.645 eV) by hydrogenation to Cmma-CH, which has potential applications in nanodevices at elevated temperatures and high voltages.

20.
ACS Omega ; 6(7): 4899-4906, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33644597

RESUMEN

In this work, we prepared CuCe/Ti catalysts in a dielectric barrier discharge (DBD) reactor and proposed a new method for flue gas mercury oxidation using DBD coupling CuCe/Ti catalyst. Our experiments verified the oxidation efficiency of flue gas Hg0 (ηHg) and clarified the influence of O2 content, NO concentration, SO2 concentration, water vapor content, and discharge voltage on ηHg. The oxidation mechanism of Hg0 in the DBD-CuCe/Ti reactor was also illustrated. The Hg0 oxidation experiment on the simulated flue gas (70 µg/m3 Hg0 + 300 mg/m3 NO + 1000 mg/m3 SO2 + 6%O2) with a flow rate of 1 L/min showed that when the amount of catalyst was 1.25 g and the discharge voltage was 9.5 kV, a ηHg of 93% can be achieved, which indicates that the DBD coupling CuCe/Ti technology is suitable for Hg0 conversion and flue gas mercury removal.

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