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Vertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), that drives myoblast fusion and muscle multinucleation. Yet they are divergent in when and where they express Mymk. In vertebrates, all developing skeletal muscles express Mymk and are obligately multinucleated. In tunicates, Mymk is only expressed in post-metamorphic multinucleated muscles, but is absent from mononucleated larval muscles. In this study, we demonstrate that cis-regulatory sequence differences in the promoter region of Mymk underlie the different spatiotemporal patterns of its transcriptional activation in tunicates and vertebrates. While in vertebrates Myogenic Regulatory Factors (MRFs) like MyoD1 alone are required and sufficient for Mymk transcription in all skeletal muscles, we show that transcription of Mymk in post-metamorphic muscles of the tunicate Ciona requires the combinatorial activity of MRF/MyoD and Early B-Cell Factor (Ebf). This macroevolutionary difference appears to be encoded in cis, likely due to the presence of a putative Ebf binding site adjacent to predicted MRF binding sites in the Ciona Mymk promoter. We further discuss how Mymk and myoblast fusion might have been regulated in the last common ancestor of tunicates and vertebrates, for which we propose two models.
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Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates MoAtg4 to attenuate the C-terminal cleavage of MoAtg8. Significantly, these two phosphorylation events maintain proper autophagy levels to coordinate the development and pathogenicity of the rice blast fungus.
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Ascomicetos , Magnaporthe , Oryza , Fosforilación , Virulencia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Magnaporthe/metabolismo , Autofagia , Pared Celular/metabolismo , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Regulación Fúngica de la Expresión GénicaRESUMEN
BACKGROUND: Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear. METHODS: Brain EC-specific CCM3-deficient (Pdcd10BECKO) mice were generated by crossing Pdcd10fl/fl mice with Mfsd2a-CreERT2 mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches. RESULTS: Single-cell RNA-sequencing analyses from P10 Pdcd10BECKO mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 Pdcd10BECKO brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the Pdcd10BECKO model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in Pdcd10BECKO mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins. CONCLUSIONS: CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.
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Células Progenitoras Endoteliales , Hemangioma Cavernoso del Sistema Nervioso Central , Diana Mecanicista del Complejo 1 de la Rapamicina , Transducción de Señal , Animales , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Ratones , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/patología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/irrigación sanguínea , Ratones Noqueados , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Ratones Endogámicos C57BL , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genéticaRESUMEN
BACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression. METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis to investigate metabolic pathways related to cancers. RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors. CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.
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Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Estudio de Asociación del Genoma Completo , Proteómica , Transcriptoma/genética , Análisis de la Aleatorización Mendeliana , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Metabolómica/métodos , Redes y Vías Metabólicas/genética , Predisposición Genética a la Enfermedad , MultiómicaRESUMEN
Mitochondria are highly dynamic organelles that constantly change their morphology to adapt to the cellular environment through fission and fusion, which is critical for a cell to maintain normal cellular functions. Despite the significance of this process in the development and pathogenicity of the rice blast fungus Magnaporthe oryzae, the underlying mechanism remains largely elusive. Here, we identified and characterized a mitochondrial outer membrane translocase, MoTom20, in M. oryzae. Targeted gene deletion revealed that MoTom20 plays an important role in vegetative growth, conidiogenesis, penetration, and infectious growth of M. oryzae. The growth rate, conidial production, appressorium turgor, and pathogenicity are decreased in the ΔMotom20 mutant compared with the wild-type and complemented strains. Further analysis revealed that MoTom20 localizes in mitochondrion and plays a key role in regulating mitochondrial fission and fusion balance, which is critical for infectious growth. Finally, we found that MoTom20 is involved in fatty-acid utilization, and its yeast homolog ScTom20 is able to rescue the defects of ΔMotom20 in mitochondrial morphology and pathogenicity. Overall, our data demonstrate that MoTom20 is a key regulator for mitochondrial morphology maintenance, which is important for infectious growth of the rice blast fungus M. oryzae. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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Proteínas Fúngicas , Mitocondrias , Oryza , Enfermedades de las Plantas , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Mitocondrias/metabolismo , Esporas Fúngicas/crecimiento & desarrollo , Ascomicetos/genética , Ascomicetos/patogenicidad , Regulación Fúngica de la Expresión Génica , Membranas Mitocondriales/metabolismo , Virulencia , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Dinámicas Mitocondriales , Eliminación de GenRESUMEN
The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.
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Proteínas Adaptadoras del Transporte Vesicular , Caspasa 8 , Enzima Desubiquitinante CYLD , Lipopolisacáridos , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Transducción de Señal , Receptor Toll-Like 4 , Caspasa 8/metabolismo , Caspasa 8/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Enzima Desubiquitinante CYLD/metabolismo , Enzima Desubiquitinante CYLD/genética , Animales , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Ratones , Humanos , Regulación de la Expresión Génica , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Proteína de Dominio de Muerte Asociada a FasRESUMEN
BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.
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Enfermedades Cardiovasculares , Humanos , Adolescente , Masculino , Femenino , Prevalencia , Estudios Transversales , Niño , Adulto Joven , Estados Unidos/epidemiología , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Encuestas Nutricionales , Factores de RiesgoRESUMEN
The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress of gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. First, the characteristics of Mettl3 expression in inflammatory bowel diseases (IBD) patients were examined. Afterward, we generated the mice line with intestinal epithelial cells (IECs)-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc. between the two groups. Subsequently, we took advantage of staining assays to analyze mucosal damage and immune infiltration of Mettl3WT and Mettl3KO primary IECs. Bulk RNA sequencing was used to pursuit the differential expression of genes (DEGs) and associated signaling pathways after losing Mettl3. Pyroptosis-related proteins were to determine whether cell death was caused by pyroptosis. Eventually, CyTOF was performed to probe the difference of CD45+ cells, especially CD3e+ T-cell clusters after losing Mettl3. In IBD patients, Mettl3 was highly expressed in the inner-nucleus of IECs while significantly decreased upon acute intestinal inflammation. IECs-specific deletion of Mettl3 KO mice triggered a wasting phenotype and developed spontaneous colitis. The survival rate, body weight, and intestinal length observed from 2 to 8 weeks of Mettl3KO mice were significantly lower than Mettl3WT mice. The degree of mucosal damage and immune infiltration in Mettl3KO were even more serious than in their WT littermate. Bulk RNA sequencing demonstrated that DEGs were dramatically enriched in NOD-signaling pathways due to the loss of Mettl3. The colonic epithelium was more prone to pyroptosis after losing Mettl3. Subsequently, CyTOF revealed that T cells have altered significantly in Mettl3KO. Furthermore, there was abnormal proliferation of CD4+ T and markedly exhaustion of CD8â +â T in Mettl3KO mice. In severe IBD patients, Mettl3 is located in the inner-nucleus of IECs and declined when intestinal inflammation occurs. Subsequently, Mettl3 prevented mice from developing colitis.
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Colitis , Disbiosis , Metiltransferasas , Animales , Ratones , Metiltransferasas/genética , Metiltransferasas/metabolismo , Colitis/inmunología , Colitis/genética , Disbiosis/genética , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Ratones Noqueados , Humanos , Linfocitos T/inmunología , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/genética , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Ratones Endogámicos C57BL , MasculinoRESUMEN
Microbe-produced secondary metabolite phenazine-1-carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection. However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence. MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host-derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G-protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity. Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.
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Ascomicetos , Magnaporthe , Oryza , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Fenazinas/metabolismo , Enfermedades de las Plantas/genéticaRESUMEN
Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.
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In this paper, a liquid crystal (LC) tunable origami metastructure (OMS) designed for curvature sensing on cylindrical surfaces to measure their curvature is introduced. The LC employed is K15 (5CB) and the applicable band is 0.36â¼23â GHz. When excited by electromagnetic waves (EMWs) within the 4â¼16â GHz, the resonance frequency of the OMS shifts from 10.24â GHz to 10.144â GHz, corresponding to a change in absorption amplitude ranging from 0.773 to 0.920. In terms of curvature sensing, the detectable range of curvature spans from 0 to 0.327â mm-1. The maximum sensitivity (S) achieved for curvature measurement reaches 0.918/mm-1, accompanied by a quality factor (Q-factor) of 25.88. The proposed OMS embodies numerous excellent traits, including wide-range sensing capabilities and heightened S, promising for applications in bionic skin, smart robotics, and related fields.
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Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CYP1A2 CpG island (CGI) and DNA methyltransferase (DNMT) 3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression. Knockdown of DNMT3A by siRNA significantly increased CYP1A2 expression in HCC cells. Additionally, treating HCC cells with decitabine (DAC) resulted in a dose-dependent upregulation of CYP1A2 expression by reducing the methylation level of CYP1A2 CGI. Furthermore, we observed a decreased enrichment of H3K27Ac in the promoter region of CYP1A2 in HCC tissues. Treatment with the trichostatin A (TSA) restored CYP1A2 expression in HCC cells by increasing H3K27Ac levels in the CYP1A2 promoter region. Importantly, combination treatment of sorafenib with DAC or TSA resulted in a leftward shift of the dose-response curve, lower IC50 values, and reduced colony numbers in HCC cells. Our findings suggest that hypermethylation of the CGI at the promoter, mediated by the high expression of DNMT3A, and hypoacetylation of H3K27 in the CYP1A2 promoter region, leads to CYP1A2 repression in HCC. Epigenetic drugs DAC and TSA increase HCC cell sensitivity to sorafenib by restoring CYP1A2 expression. Our study provides new insights into the epigenetic regulation of CYP1A2 in HCC and highlights the potential of epigenetic drugs as a therapeutic approach for HCC. SIGNIFICANCE STATEMENT: This study marks the first exploration of the epigenetic mechanisms underlying cytochrome P450 (CYP) 1A2 suppression in hepatocellular carcinoma (HCC). Our findings reveal that heightened DNA methyltransferase expression induces hypermethylation of the CpG island at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine and trichostatin A emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.
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Carcinoma Hepatocelular , Citocromo P-450 CYP1A2 , Metilación de ADN , Epigénesis Genética , Neoplasias Hepáticas , Sorafenib , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Humanos , Sorafenib/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/genética , Metilación de ADN/efectos de los fármacos , Línea Celular Tumoral , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , ADN Metiltransferasa 3A , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Decitabina/farmacología , Islas de CpG/genética , Ácidos Hidroxámicos/farmacología , Regiones Promotoras Genéticas/genética , Regiones Promotoras Genéticas/efectos de los fármacosRESUMEN
We present a corrigendum to our Letter [Opt. Lett.48, 5699 (2023)10.1364/OL.505761]. In section 3 of the original supplementary material, the absolute value is incorrectly taken in resolving the Kubo formula for describing the conductivity of graphene. Because this is a mistake with the conductivity of graphene, the coupling of the original structure is broken when the correct result is inserted into the code of the transfer matrix. So, the structure of the arithmetic logic unit (ALU), characteristic frequency point, and phase control have been modified accordingly. However, the ultimate function and the conclusion of this work remain unchanged.
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Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.
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Epilepsia , Ferroptosis , Hipocampo , Magnesio , Neuronas , Ratas Sprague-Dawley , Animales , Ferroptosis/fisiología , Ferroptosis/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Magnesio/metabolismo , Ratas , Epilepsia/metabolismo , Epilepsia/patología , Células Cultivadas , Proteínas de Unión al ARN/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , MicroARNs/metabolismo , MicroARNs/genética , Especies Reactivas de Oxígeno/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismoRESUMEN
A Gram-stain-negative, rod-shaped, indole-producing, and cellulose-degrading bacterial strain, designated NEAU-G-C5T, was isolated from soil collected from a forest in Dali city, Yunnan province, south China. 16S rRNA gene sequence analysis showed that strain NEAU-G-C5T was assigned to the genus Massilia and showed high sequence similarities to Massilia phosphatilytica 12-OD1T (98.32â%) and Massilia putida 6 NM-7T (98.41â%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-G-C5T formed a lineage related to M. phosphatilytica 12-OD1T and M. putida 6 NM-7T. The major fatty acids of the strain were C16â:â0, C16â:â1 ω7c, and C17â:â0 cyclo. The respiratory quinone was Q-8. The polar lipid profile of the strain showed the presence of diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. In addition, the average nucleotide identity values between strain NEAU-G-C5T and its reference strains M. phosphatilytica 12-OD1T, M. putida 6 NM-7T, M. norwichensis NS9T, and M. kyonggiensis TSA1T were 89.7, 88.2, 81.3, and 88.0â%, respectively, and the levels of digital DNA-DNA hybridization between them were found to be 58.5â% (54.9-62.0â%), 53.2â% (49.8-56.7â%), 31.9â% (28.6-35.5â%), and 57.7â% (54.1-61.2â%), respectively, which were lower than the accepted threshold values of 95-96â% and 70â%, respectively. The DNA G+C content of strain NEAU-G-C5T was 66.5âmol%. The strain could produce indoleacetic acid and cellulase. On the basis of the phenotypic, genotypic, and chemotaxonomic characteristics, we conclude that strain NEAU-G-C5T represents a novel species of the genus Massilia, for which the name Massilia luteola sp. nov. is proposed. The type strain is NEAU-G-C5T (=MCCC 1K08668T=KCTC 8080T).
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Ácidos Grasos , Fosfolípidos , Ácidos Grasos/química , Fosfolípidos/análisis , Suelo , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Análisis de Secuencia de ADN , Composición de Base , China , Técnicas de Tipificación Bacteriana , Indoles , Microbiología del SueloRESUMEN
AIM: To assess the association of Life's Essential 8 (LE8) and the presence of abdominal aortic calcification (AAC) with mortality among middle-aged and older individuals. METHODS: Participants aged older than 40 years were enrolled from the National Health and Nutrition Examination Survey 2013-2014. AAC was assessed using dual-energy X-ray absorptiometry. Mortality data were ascertained through linkage with the National Death Index until 31 December 2019. The LE8 score incorporates eight components: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose and blood pressure. The total LE8 score, an unweighted average of all components, was categorized into low (0-49), medium (50-79) and high (80-100) scores. RESULTS: This study included 2567 individuals, with a mean LE8 score of 67.28 ± 0.48 and an AAC prevalence of 28.28%. Participants with low LE8 scores showed a significantly higher prevalence of AAC (odds ratio = 2.12 [1.12-4.19]) compared with those with high LE8 scores. Over a median 6-year follow-up, there were 222 all-cause deaths, and 55 cardiovascular deaths occurred. Participants with AAC had an increased risk of all-cause (hazard ratio [HR] = 2.17 [1.60-2.95]) and cardiovascular (HR = 2.35 [1.40-3.93]) mortality. Moreover, individuals with AAC and low or medium LE8 scores exhibited a 137% (HR = 2.37 [1.58-3.54]) and 119% (HR = 2.19 [1.61-2.99]) higher risk of all-cause mortality, as well as a 224% (HR = 3.24 [1.73-6.04]) and 125% (HR = 2.25 [1.24-4.09]) increased risk of cardiovascular mortality, respectively. CONCLUSIONS: The LE8 score correlates with AAC prevalence in middle-aged and older individuals and serves as a valuable tool for evaluating the risk of all-cause and cardiovascular mortality in individuals with AAC.
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AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/etiología , Reino Unido/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Adulto , Factores de Riesgo , Índice de Masa Corporal , Fumar/efectos adversos , Fumar/epidemiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Ejercicio Físico , Estudios de Seguimiento , Presión Sanguínea , IncidenciaRESUMEN
A one-dimensional optical biosensing metastructure (OBM) with graphene layers is presented in this paper. It is realized by coherent perfect absorption (CPA) and operates in the transverse electric mode. It shows a strong linear fitting relationship between the refractive index (RI) of the analysis layer and the frequency corresponding to the absorption peak, and the R-square is up to 1. Additionally, based on the principle of CPA, the OBM can realize the function of multiple cancer cell detection by adjusting the detection range by controlling the phase difference of coherent electromagnetic waves. Its detection ranges are 1.34-1.355 and 1.658-1.662. Thanks to its high-quality factor, great figure of merit, and low detection limit, whose best values are, respectively, 6.9 × 104, 1.2 × 104 RIU-1, and 3.6 × 10-6 RIU, the detection of weak changes in the RI of a cancer cell is possible. Additionally, its sensitivity can reach 26.57 THz RIU-1. This OBM based on CPA has major implications for advancing the study and investigation into the application of CPA. It also provides a simple and efficient approach to distinguish cancer cells and may be widely used in the biomedical field.
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Grafito , Neoplasias , Humanos , Electricidad , Neoplasias/diagnósticoRESUMEN
BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.
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Aneurisma de la Aorta , Disección Aórtica , Ácido Ascórbico , Factores Protectores , Vitamina E , Humanos , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Femenino , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/efectos adversos , Vitamina E/administración & dosificación , Factores de Riesgo , Anciano , Incidencia , Disección Aórtica/epidemiología , Disección Aórtica/prevención & control , Aneurisma de la Aorta/epidemiología , Aneurisma de la Aorta/prevención & control , Medición de Riesgo , Reino Unido/epidemiología , Factores de Tiempo , Dieta/efectos adversos , AdultoRESUMEN
BACKGROUND: The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. METHODS: A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. RESULTS: Over a median follow-up of 12.8 years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. CONCLUSIONS: An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.