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Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium-sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium-sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium-sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm-2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm-2 and electrolyte dosage of 4.8 µL mg-1.
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Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.
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Mesothelioma, an uncommon yet highly aggressive malignant neoplasm, presents challenges in the effectiveness of current therapeutic approaches. Ferroptosis, a non-apoptotic mechanism of cellular demise, exhibits a substantial association with the progression of diverse cancer forms. It is important to acknowledge that there exists a significant association between ferroptosis and the advancement of various forms of cancer. Nevertheless, the precise role of ferroptosis regulatory factors within the context of mesothelioma remains enigmatic. In our investigation, we initially scrutinized the prognostic significance of 24 ferroptosis regulatory factors in the realm of mesothelioma. Our observations unveiled that heightened expression levels of CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, coupled with reduced DPP4 expression, were indicative of an unfavorable prognosis. Built upon the nine previously discussed prognostic genes, the ferroptosis prognostic model offers a reliable means to forecast mesothelioma patients' survival with a substantial degree of precision. Furthermore, a notable correlation emerged between these prognostic ferroptosis regulators and parameters such as immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression in the context of mesothelioma. Within this cadre of nine ferroptosis regulatory factors with prognostic relevance, FANCD2 exhibited the most pronounced prognostic influence, as elucidated by our analyses. Subsequently, we executed a validation process employing clinical specimens sourced from our institution, thus confirming that heightened FANCD2 expression is a discernible harbinger of an adverse prognosis in the context of mesothelioma. In vitro experiments revealed that knocking down FANCD2 markedly suppressed the proliferation, migration, and ability of mesothelioma cells to attract immune cells. Furthermore, our findings also showed that reducing FANCD2 levels heightened the vulnerability of mesothelioma cells to inducers of ferroptosis. Furthermore, an extensive pan-cancer analysis uncovered a robust association between FANCD2 and the gene expression linked to immune checkpoints, thereby signifying an adverse prognosis across a broad spectrum of cancer types. Additional research is warranted to validate these findings.
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Ferroptosis , Regulación Neoplásica de la Expresión Génica , Mesotelioma , Ferroptosis/genética , Humanos , Pronóstico , Mesotelioma/genética , Mesotelioma/patología , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/metabolismo , Línea Celular Tumoral , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mesotelioma Maligno/genética , Mesotelioma Maligno/patología , Sistema de Transporte de Aminoácidos y+RESUMEN
BACKGROUND & AIMS: The functional maturation of the liver largely occurs after birth. In the early stages of life, the liver of a newborn encounters enormous high-fat metabolic stress caused by the consumption of breast milk. It is unclear how the maturing liver adapts to high lipid metabolism. Liver sinusoidal endothelial cells (LSECs) play a fundamental role in establishing liver vasculature and are decorated with many glycoproteins on their surface. The Slc35a1 gene encodes a cytidine-5'-monophosphate (CMP)-sialic acid transporter responsible for transporting CMP-sialic acids between the cytoplasm and the Golgi apparatus for protein sialylation. This study aimed to determine whether endothelial sialylation plays a role in hepatic vasculogenesis and functional maturation. METHODS: Endothelial-specific Slc35a1 knockout mice were generated. Liver tissues were collected for histologic analysis, lipidomic profiling, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. RESULTS: Endothelial Slc35a1-deficient mice exhibited excessive neonatal hepatic lipid deposition, severe liver damage, and high mortality. Endothelial deletion of Slc35a1 led to sinusoidal capillarization and disrupted hepatic zonation. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) in LSECs was desialylated and VEGFR2 signaling was enhanced in Slc35a1-deficient mice. Inhibition of VEGFR2 signaling by SU5416 alleviated lipid deposition and restored hepatic vasculature in Slc35a1-deficient mice. CONCLUSIONS: Our findings suggest that sialylation of LSECs is critical for maintaining hepatic vascular development and lipid homeostasis. Targeting VEGFR2 signaling may be a new strategy to prevent liver disorders associated with abnormal vasculature and lipid deposition.
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Células Endoteliales , Metabolismo de los Lípidos , Hígado , Ratones Noqueados , Animales , Ratones , Hígado/metabolismo , Hígado/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Proteínas de Transporte de Nucleótidos/metabolismo , Proteínas de Transporte de Nucleótidos/genética , Animales Recién Nacidos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Perinatal depression (PND) is a common mental health problem, and eHealth interventions may provide a strategy for alleviating PND. AIM: This meta-analysis aimed to determine the effect of eHealth interventions on PND. METHODS: Six databases were searched to retrieve published randomized controlled trials (RCTs) on the effect of eHealth interventions on PND. A meta-analysis was performed on the data of these studies using a random effects model. RESULTS: A total of 21 RCTs were included in the meta-analysis, which revealed that eHealth interventions significantly reduced antenatal depression (WMD = -1.64, 95 % CI [-2.92, -0.35], P = .013), postpartum depression (SMD = -0.41, 95 % CI [-0.52, -0.29], P < .001), anxiety (SMD = -0.39, 95 % CI [-0.51, -0.28], P < .001), stress (WMD = -2.93, 95 % CI [-4.58, -1.27], P = .001), and improved self-efficacy (SMD = 0.42, 95 % CI [0.21, 0.63], P < .001) compared with the control group. However, eHealth interventions did not significantly improve social support (SMD = 0.27, 95 % CI [-0.01, 0.56], P = .058). For antenatal depression, significant subgroup differences were observed in the digital platform and material presentation format. In addition, for postpartum depression, significant subgroup differences were found in the type of therapy. CONCLUSIONS: The meta-analysis results suggest that eHealth interventions can relieve depression, anxiety, and stress symptoms and improve self-efficacy in perinatal women. However, these interventions did not improve social support. Additional high-quality studies on eHealth interventions in PND are needed to validate these results.
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Depresión Posparto , Trastorno Depresivo , Telemedicina , Embarazo , Femenino , Humanos , Depresión/terapia , Depresión/diagnóstico , Depresión Posparto/terapia , Ansiedad/terapia , Telemedicina/métodos , Calidad de VidaRESUMEN
This study aimed to investigate the molecular mechanisms underlying the aging of hematopoietic stem cells (HSCs). Gene expression profile GSE32719 was downloaded from the Gene Expression Omnibus database, including 14 young, 5 middle, and 8 old HSCs. Differential expression analysis, short time-series expression miner analysis, and weighted co-expression network analysis were conducted to screen for hub genes whose expression changed over time during HSC aging. Subsequently, functional enrichment and multiple regulatory network analyses of the hub genes were performed. A total of 124 intersecting time-dependent differentially expressed and module genes were obtained, which were considered hub genes whose expression changed over time during HSC aging. Hub genes were significantly enriched in pathways such as the Hippo and AMP-activated protein kinase (AMPK) signaling pathways. Moreover, AP-1 Transcription Factor Subunit (FOS) and sirtuin 1 (SIRT1) had higher degrees in the protein-protein interaction network, were regulated by more transcription factors (TFs), such as Sp1 transcription factor (SP1) and BRCA1 DNA repair-associated (BRCA1), in the TF-mRNA-miRNA network, were associated with more diseases in the disease-gene network, and could be targeted by more drugs in the drug-gene network. Furthermore, SIRT1 was targeted by miR-9-5p in the TF-mRNA-miRNA network. Hub genes such as FOS and SIRT1 and key pathways such as the Hippo and AMPK signaling pathways may play crucial roles in HSC aging. Moreover, FOS and SIRT1 were regulated by SP1 and BRCA1, respectively, during HSC aging. Furthermore, miR-9-5p may modulate HSC aging by targeting SIRT1. Thus, FOS and SIRT1 may be potential therapeutic targets for age-related hematopoietic dysfunction.
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Perfilación de la Expresión Génica , MicroARNs , Humanos , Proteínas Quinasas Activadas por AMP/genética , Sirtuina 1/genética , MicroARNs/genética , Factores de Transcripción/genética , Redes Reguladoras de Genes , Células Madre Hematopoyéticas , ARN Mensajero , Biología ComputacionalRESUMEN
Seven new terpenoids, including six sacculatane diterpenoids plagiochilarins A-F (1-6), and one ent-2,3-seco-aromandrane sesquiterpenoid plagiochilarin H (8) with a 6/7/3/5 tetracyclic scaffold, alongside three known compounds, were obtained from the Chinese liverwort Plagiochila nitens Inoue. Plagiochilarin B (2) was unpredictably converted to the more stable artifact 7 under acid catalysis through cyclic ether formation. The reaction mechanism was reasonably deduced and experimentally verified. The structures of these terpenoids were determined by analysis of MS and NMR spectroscopic data and single-crystal X-ray diffraction. The inhibitory effect of all of the isolates was evaluated on the growth of two C. albicans strains, wild strain SC5314 and efflux pump-deficient strain DSY654. However, only plagiochilarin H (8) showed a MIC value of 16 µg/mL against C. albicans DSY654.
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Candida albicans , Diterpenos , Hepatophyta , Hepatophyta/química , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , China , Candida albicans/efectos de los fármacos , Estructura Molecular , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Cristalografía por Rayos XRESUMEN
The primary objective of science postgraduate education is to foster students' capacity for creative thinking and problem-solving, particularly in the context of scientific research quality. In order to achieve this goal, the "7E" teaching mood has been implemented in the cell biology course for postgraduate students to promote student-centered active inquiry learning instead of breaking away from traditional indoctrination-based teaching methods. This study demonstrates that the implementation of the "7E" teaching mode, through content programming, process design, and effect evaluation, effectively meets the needs of the majority of students, fosters their interest in learning, enhances their performance in comprehensive questioning, and enhances their innovative abilities in scientific research. Consequently, this research offers a theoretical framework and practical foundation for the development of the "7E" teaching mode in postgraduate courses, aiming to cultivate highly skilled scientific professionals.
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Biología Celular , Aprendizaje Basado en Problemas , Estudiantes , Humanos , Estudiantes/psicología , Aprendizaje Basado en Problemas/métodos , Biología Celular/educación , Enseñanza , Curriculum , Educación de Postgrado/métodos , AprendizajeRESUMEN
ABSTRACT: Glucosamine (UDP-N-acetyl)-2-epimerase and N-acetylmannosamine (ManNAc) kinase (GNE) is a cytosolic enzyme in de novo sialic acid biosynthesis. Congenital deficiency of GNE causes an autosomal recessive genetic disorder associated with hereditary inclusion body myopathy and macrothrombocytopenia. Here, we report a pediatric patient with severe macrothrombocytopenia carrying 2 novel GNE missense variants, c.1781G>A (p.Cys594Tyr, hereafter, C594Y) and c.2204C>G (p.Pro735Arg, hereafter, P735R). To investigate the biological significance of these variants in vivo, we generated a mouse model carrying the P735R mutation. Mice with homozygous P735R mutations exhibited cerebral hemorrhages as early as embryonic day 11 (E11), which subsequently progressed to large hemorrhages in the brain and spinal cord, and died between E11.5 and E12.5. Defective angiogenesis such as distended vascular sprouts were found in neural tissues and embryonic megakaryocytes were abnormally accumulated in the perineural vascular plexus in mutant mouse embryos. Furthermore, our in vitro experiments indicated that both C594Y and P735R are loss-of-function mutations with respect to de novo sialic acid biosynthesis. Overall, this study reveals a novel role for GNE-mediated de novo sialic acid biosynthesis in mouse embryonic angiogenesis.
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Angiogénesis , Ácido N-Acetilneuramínico , Animales , Niño , Humanos , Ratones , Encéfalo , Mutación , Mutación MissenseRESUMEN
Hydrogen peroxide is widely used to remedy bacterial and parasitic infections, but its excessive use will cause severe damage to aquatic animals. Moreover, there is no safe, efficient and low-cost method to degrade residual hydrogen peroxide in water. Here we developed a hydrogen peroxide removal mechanism by which autoinducer-2 (AI-2), a quorum sensing signal molecule that can promote the hydrogen peroxide degradation by Gram-positive bacteria. Here, we investigated the promotion effect of AI-2 on hydrogen peroxide degradation by Deinococcus sp. Y35 and the response of the antioxidant system. We further sought to understand the key mechanism underlying the promotion effect of AI-2 on hydrogen peroxide degradation is that, AI-2 contributed to the resistance of strain Y35 to oxidative stress induced by hydrogen peroxide, and altered membrane permeability of strain Y35 that allowed more hydrogen peroxide to enter bacterial cells and be degraded. Additionally, AI-2 can also encourage multiple Gram-positive bacteria to degrade hydrogen peroxide. Accordingly, our study serves as a reference for the regulation mechanism of the signal molecule AI-2 and provides the development of new strategies for hydrogen peroxide degradation.
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Homoserina/análogos & derivados , Peróxido de Hidrógeno , Percepción de Quorum , Animales , Peróxido de Hidrógeno/farmacología , Agua , Lactonas/metabolismo , Bacterias Grampositivas , Proteínas Bacterianas/metabolismoRESUMEN
The objectives of this study were to evaluate the difference of selective attention efficiency between children with low and high socioeconomic status (SES) and the promotional effect of attention network training (an attention network test was used as the training task) on selective attention in children with the low SES. A total of 139 10- to 12-year-old children participated in two experiments (71 in Experiment 1 and 68 in Experiment 2). The results suggest that selective attention and switch ability of children with high SES are better than those of children with low SES. After attention network training, selective attention, switch ability, and working memory of low-SES children improved significantly. The findings provide evidence that attention network training could enhance selective attention in low-SES children and that the beneficial training effect could also transfer to switch ability and working memory. The research may provide a promising method to compensate cognitive delay of low-SES children.
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Estatus Socioeconómico Bajo , Clase Social , Niño , Humanos , Memoria a Corto Plazo , Electroencefalografía , AtenciónRESUMEN
The viscosity within cells is a crucial microenvironmental factor, and sulfur dioxide (SO2 ) has essential functions in regulating cellular apoptosis and inflammation. Some evidence has been confirmed that changes in viscosity and overexposure of SO2 within the cell may cause detrimental effects including, but not limited to, respiratory and cardiovascular illnesses, inflammation, fatty liver, and various types of cancer. Therefore, precise monitoring of SO2 and viscosity in biological entities holds immense practical importance. Therefore, in this research, we developed a versatile fluorescent TCF-Cou that enables the dual detection of SO2 and viscosity in the living system. Probe TCF-Cou possessed a response to viscosity and SO2 through red and green emissions. The alteration of SO2 and viscosity levels in live cells and zebrafish were also monitored using probe TCF-Cou. We hope that this fluorescent probe could be a potential tool for revealing the related pathological and physiological processes through monitoring the changes in SO2 and viscosity.
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Colorantes Fluorescentes , Pez Cebra , Humanos , Animales , Células HeLa , Viscosidad , Dióxido de AzufreRESUMEN
INTRODUCTION: Ubiquitination is a significant post-translational modification engaged in diverse biological processes, such as cell differentiation, metastasis, and protein stability modulation. The dysregulation of ubiquitination and deubiquitination is inextricably linked to disease progression, including preeclampsia (PE). Ubiquitin-specific protease 17 (USP17), a prominent deubiquitinating enzyme that regulates ubiquitination modifications, performs multiple functions at the cellular level, whereas its role in PE remains elusive. In this study, we intended to probe the role of USP17 in PE and its underlying mechanisms. METHODS: The USP17 level in the plasma of PE patients was detected through Elisa. Western blot and qRT-PCR were performed to measure the mRNA and protein level of USP17 in placental tissues. CCK-8, EdU, and transwell assays were conducted to evaluate the proliferation, migration, and invasion of trophoblast cells. The interaction between HDAC2 and USP17 or STAT1 were determined by co-immunoprecipitation and Western blot assays. The expression of NF-κB pathway related proteins was examined using Western blot. RESULTS: USP17 was dramatically downregulated in PE patients. Overexpression of USP17 facilitated trophoblast proliferation, migration, and invasion. Moreover, histone deacetylase 2 (HDAC2) was validated as a substrate of USP17 deubiquitination, and USP17 upregulation enhanced HDAC2 protein level. Furthermore, HDAC2 could interact with and deacetylate Signal transducer and activator of transcription 1 (STAT1), resulting in the enhancement of STAT1 activity and inhibition of NF-κB signaling. DISCUSSION: Our findings disclosed that USP17 augmented the proliferation and invasion of trophoblast by deubiquitinating HDAC2, which will contribute to novel prospective targets for diagnosing and treating PE.
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FN-kappa B , Preeclampsia , Humanos , Femenino , Embarazo , FN-kappa B/metabolismo , Histona Desacetilasa 2/genética , Preeclampsia/metabolismo , Placenta/metabolismo , Transducción de Señal , Trofoblastos/metabolismo , Proliferación Celular , Movimiento Celular/genéticaRESUMEN
Peripheral T-cell lymphoma (PTCL) is a clinically heterogeneous group that represents 10%-15% of all lymphomas. Despite improved genetic and molecular understanding, treatment outcomes for PTCL have not shown significant improvement. Although Janus kinase-2 (JAK2) plays an important role in myeloproliferative neoplasms, the critical role of JAK isoforms in mediating prosurvival signaling in PTCL cells is not well defined. Immunohistochemical analysis of PTCL tumors (n = 96) revealed high levels of constitutively active JAK3 (pJAK3) that significantly (p < 0.04) correlated with the activation state of its canonical substrate STAT3. Furthermore, constitutive activation of JAK3 and STAT3 positively correlated, at least in part, with an oncogenic tyrosine phosphatase PTPN11. Pharmacological inhibition of JAK3 but not JAK1/JAK2 significantly (p < 0.001) decreased PTCL proliferation, survival and STAT3 activation. A sharp contrast was observed in the pJAK3 positivity between ALK+ (85.7%) versus ALK-negative (10.0%) in human PTCL tumors and PTCL cell lines. Moreover, JAK3 and ALK reciprocally interacted in PTCL cells, forming a complex to possibly regulate STAT3 signaling. Finally, combined inhibition of JAK3 (by WHI-P154) and ALK (by crizotinib or alectinib) significantly (p < 0.01) decreased the survival of PTCL cells as compared to either agent alone by inhibiting STAT3 downstream signaling. Collectively, our findings establish that JAK3 is a therapeutic target for a subset of PTCL, and provide rationale for the clinical evaluation of JAK3 inhibitors combined with ALK-targeted therapy in PTCL.
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Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/genética , Línea Celular Tumoral , Transducción de Señal , Fosforilación , Proteínas Tirosina Quinasas Receptoras , Janus Quinasa 3RESUMEN
A major cellobiohydrolase of Neurospora crassa CBH2 was successfully expressed in Pichia pastoris. The maximum Avicelase activity in shake flask among seven transformants which selected on 4.0 g/L G418 plates was 0.61 U/mL. The optimal pH and temperature for Avicelase activity of the recombinant CBH2 were determined to be 4.8 and 60 °C, respectively. The new CBH2 maintained 63.5 % Avicelase activity in the range of pH 4.0-10.4, and 60.2 % Avicelase activity in the range of 30-90 °C. After incubation at 70-90 °C for 1 h, the Avicelase activity retained 60.5 % of its initial activity. The presence of Zn2+, Ca2+ or Cd2+ enhanced the Avicelase activity of the CBH2, of which Cd2+ at 10 mM causing the highest increase. The recombinant CBH2 was used to enhance the Avicel hydrolysis by improving the exo-exo-synergism between CBH2 and CBH1 in N.crassa cellulase. The enzymatic hydrolysis yield was increased by 38.1 % by adding recombinant CBH2 and CBH1, and the yield was increased by 215.4 % when the temperature is raised to 70 °C. This work provided a CBH2 with broader pH range and better heat resistance, which is a potential enzyme candidate in food, textile, pulp and paper industries, and other industrial fields.
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Celulosa 1,4-beta-Celobiosidasa , Neurospora crassa , Saccharomycetales , Celulosa 1,4-beta-Celobiosidasa/genética , Neurospora crassa/genética , Neurospora crassa/metabolismo , Cadmio , Pichia/genética , Pichia/metabolismo , Clonación Molecular , Proteínas RecombinantesRESUMEN
Heart aging is a prevalent cause of cardiovascular diseases among the elderly. NAD+ depletion is a hallmark feature of aging heart, however, the molecular mechanisms that affect NAD+ depletion remain unclear. In this study, we identified microRNA-203 (miR-203) as a senescence-associated microRNA that regulates NAD+ homeostasis. We found that the blood miR-203 level negatively correlated with human age and its expression significantly decreased in the hearts of aged mice and senescent cardiomyocytes. Transgenic mice with overexpressed miR-203 (TgN (miR-203)) showed resistance to aging-induced cardiac diastolic dysfunction, cardiac remodeling, and myocardial senescence. At the cellular level, overexpression of miR-203 significantly prevented D-gal-induced cardiomyocyte senescence and mitochondrial damage, while miR-203 knockdown aggravated these effects. Mechanistically, miR-203 inhibited PARP1 expression by targeting its 3'UTR, which helped to reduce NAD+ depletion and improve mitochondrial function and cell senescence. Overall, our study first identified miR-203 as a genetic tool for anti-heart aging by restoring NAD+ function in cardiomyocytes.
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Cardiopatías , MicroARNs , Ratones , Humanos , Animales , Anciano , NAD/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Senescencia Celular/genética , Ratones Transgénicos , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
Introduction: Acute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m6A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance. Methods: To investigate the m6A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m6A modification activity of cells in AML patients based on 23 m6A modification enzymes and further integrated with bulk RNA-seq data. Results: We found that m6A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m6A modification status in leukemia cells, while active m6A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m6A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by RUNX1 mutation and KMT2A copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of IGF2BP3 and FMR1, and low expression level of ELAVL1 and YTHDF2. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings suggest that m6A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.
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Variaciones en el Número de Copia de ADN , Leucemia Mieloide Aguda , Humanos , RNA-Seq , Análisis de Expresión Génica de una Sola Célula , Pronóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Factores de Transcripción , Resistencia a Medicamentos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X FrágilRESUMEN
Background: Non-melanoma skin cancer (NMSC) is a prevalent skin malignancy. It has been indicated in many studies that trihalomethanes (THMs) exposure has a strong association with tumors but has not been associated with NMSC. Our investigation aims to explore the association between THMs exposure and NMSC. Methods: Cross-sectional data from the 2011 to 2020 National Health and Nutrition Examination Survey (NHANES) was collected. Poisson regression and subgroup analyses were performed to evaluate the association between individual THMs components and NMSC. Fitted smoothing curves and generalized additive models were also used. Results: This study involved 5,715 individuals, 98 (1.7%) of whom self-reported NMSC. After adjusting for covariates, Poisson regression showed that higher blood TBM levels were associated with an increased likelihood of NMSC (OR = 1.03; 95% CI: 1.01-1.05, p = 0.002). However, the correlation between the blood levels of TCM, DBCM, and BDCM and the likelihood of NMSC was not statistically significant (all p > 0.05). Subgroup analysis and interaction tests showed no significant differences between blood TBM concentration and the likelihood of NMSC, indicating that age, gender, and race were significantly independent of this positive association (all p < 0.05). Conclusions: Our results implied that among adults older than 65 years old in the U.S., elevated blood TBM concentrations were positively associated with NMSC. More prospective investigations are required to validate this relationship with the early prevention of NMSC.
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Neoplasias Cutáneas , Trihalometanos , Adulto , Humanos , Anciano , Encuestas Nutricionales , Estudios Transversales , Estudios Prospectivos , Neoplasias Cutáneas/epidemiologíaRESUMEN
The dynamical hypothesis has served to explore the ways in which cognitive agents can be understood dynamically and considered dynamical systems. Originally used to explain simple physical systems as a metaphor for cognition (i.e., the Watt governor) and eventually more complex animal systems (e.g., bird flocks), we argue that the dynamical hypothesis is among the most viable approaches to understanding pressing modern-day issues that arise from collective human behavior in online social networks. First, we discuss how the dynamical hypothesis is positioned to describe, predict, and explain the time-evolving nature of complex systems. Next, we adopt an interdisciplinary perspective to describe how online social networks are appropriately understood as dynamical systems. We introduce a dynamical modeling approach to reveal information about emergent properties in social media, where radicalized conspiratorial beliefs arise via coordination between user-level and community-level comments. Lastly, we contrast how the dynamical hypothesis differs from alternatives in explaining collective human behavior in social networks.