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Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2's histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.
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Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Cohesinas , Replicación del ADN , Proteínas de Unión al ADN , Células-Madre Neurales , Animales , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Cromatina/metabolismo , Origen de Réplica , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Genoma/genética , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Ratones NoqueadosRESUMEN
Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.
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Deficiencia de Vitamina A , Vitamina A , Femenino , Ratas , Animales , Alimentos Fortificados , Estudios Cruzados , Culinaria , MicronutrientesRESUMEN
3-phosphoinositide-dependent protein kinase 1 (PDK1) exhibits a substantial influence on immune cell development by establishing a vital connection between PI3K and downstream mTOR signaling cascades. However, it remains unclear whether PDK1 signaling affects the homeostasis and functionality of immune cells. To explore the impact of PDK1 on different immune cells within immune organs, transgenic mouse strains with lymphocyte-specific PDK1 knockout (PDK1fl/fl CD2-Cre) were generated. Unlike wild-type (WT) mice, lymphocyte-specific PDK1 knockout (KO) mice exhibited thymic atrophy, elevated percentages of CD8+ T cells and neutrophils, and reduced proportions of γδ T cells, B cells, and NK cells in the spleen. Functional analysis revealed elevated release of IFN-γ and IL-17A by T cells in PDK1 KO mice, contrasting with diminished levels observed in γδ T cells and Treg cells. Furthermore, the activation, cytotoxicity, and migratory potential of γδ T cells in PDK1 KO mice are heightened, indicating a potential association with the regulation of the mTOR signaling pathway. To conclude, the findings of this research demonstrated that specific knockout of PDK1 in lymphocytes hindered T cell development in the thymus and exhibited a substantial influence on immune cell homeostasis in the spleen and lymph nodes.
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Ratones Noqueados , Timo , Animales , Ratones , Timo/inmunología , Bazo/inmunología , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/metabolismo , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/genética , Transducción de Señal , Ratones Endogámicos C57BL , Serina-Treonina Quinasas TOR/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/genética , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Interleucina-17/metabolismo , Interleucina-17/inmunología , Linfocitos T CD8-positivos/inmunologíaRESUMEN
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. RESULTS: The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7-260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P < 0.0001) and healthy women [49.6 (35.5-78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLDs than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV1%pred, FEV1/FVC, and DLCO%pred (P = 0.0181, r = - 0.3398; P = 0.0067, r = - 0.3863; P = 0.0010, r = - 0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone. CONCLUSION: Higher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.
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Linfangioleiomiomatosis , Proteínas de Microfilamentos , Humanos , Femenino , Linfangioleiomiomatosis/diagnóstico , Factor D de Crecimiento Endotelial Vascular , Biomarcadores , SirolimusRESUMEN
The self-assembly of the lanthanide metal-organic frameworks presents a formidable challenge but profound significance. Compared with the metal-organic frameworks based on 4f-3d ions, the chemistry of 4f-3p metal-organic frameworks has not been fully explored so far. In this study, two lanthanide-aluminum-based clusters [Ln6Al(IN)10(µ3-OH)5(µ3-O)3(H2O)8]·xH2O (x = 2, Ln = Gd, abbreviated as Gd6Al; x = 2.5, Ln = Eu, abbreviated as Eu6Al; HIN = isonicotinic acid) have been meticulously designed and obtained by hydrothermal reaction at low pH. The crystallographic study revealed that both Gd6Al and Eu6Al clusters exhibit an unprecedented sandwiched metal-organic framework holding a highly ordered honeycomb network. To our knowledge, it is the first case of Ln-Al-based cluster-organic frameworks. Furthermore, magnetic investigation of Gd6Al manifests a decent magnetic entropy change of -ΔSmmax = 28.8 J kg-1 K-1 at 2 K for ΔH = 7.0 T. Significantly, the introduction of AlIII ions into the lanthanide metal-organic frameworks displays excellent solid-state luminescent capability with a lifetime of 371.6 µs and quantum yield of 6.64%. The construction and investigation of these two Ln-Al clusters represent great progress in the 4f-3p metal-organic framework.
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SETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark. Apart from its H3K9me3 regulatory role, SETDB1 has seldom been studied in terms of its other potential regulatory roles. To investigate this, a genomic survey of SETDB1 binding in mouse embryonic stem cells across multiple libraries was conducted, leading to the unexpected discovery of regions bereft of common repressive histone marks (H3K9me3, H3K27me3). These regions were enriched with the CTCF motif that is often associated with the topological regulator Cohesin. Further profiling of these non-H3K9me3 regions led to the discovery of a cluster of non-repeat loci that were co-bound by SETDB1 and Cohesin. These regions, which we named DiSCs (domains involving SETDB1 and Cohesin) were seen to be proximal to the gene promoters involved in embryonic stem cell pluripotency and lineage development. Importantly, it was found that SETDB1-Cohesin co-regulate target gene expression and genome topology at these DiSCs. Depletion of SETDB1 led to localized dysregulation of Cohesin binding thereby locally disrupting topological structures. Dysregulated gene expression trends revealed the importance of this cluster in ES cell maintenance as well as at gene 'islands' that drive differentiation to other lineages. The 'unearthing' of the DiSCs thus unravels a unique topological and transcriptional axis of control regulated chiefly by SETDB1.
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Retrovirus Endógenos , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Retrovirus Endógenos/metabolismo , Genómica , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Ratones , CohesinasRESUMEN
BACKGROUND: Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. METHODS: A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. RESULTS: A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. CONCLUSION: The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.
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Obstrucción de las Vías Aéreas , Asma , Humanos , Sobrepeso/epidemiología , Calidad de Vida , Asma/tratamiento farmacológico , Obstrucción de las Vías Aéreas/epidemiología , Obesidad/epidemiologíaRESUMEN
Multiple sclerosis (MS) is a common autoimmunity disease of the central nervous system (CNS) that mostly happens in young adults. The chronic clinical features of MS include inflammatory demyelination, infiltration of immune cells, and secretion of inflammatory cytokines, which have been proved to be associated with CD4+ T cells. Ferroptosis is a newly discovered programmed cell death mediated by the massive lipid peroxidation and more sensitive to CD4+ T cells. However, the effect of ferroptosis of CD4+ T cells on the occurrence and progression of MS retains unclear. Here, the experimental autoimmune encephalomyelitis (EAE) model was used to investigate the role of GPX4, a leading inhibitor of ferroptosis, which plays in the function of CD4+ T cells. Our results showed that GPX4 was highly expressed in CD4+ T cells of MS patients based on existing databases. Strikingly, conditional knockout of GPX4 in CD4cre mice (cKO mice) significantly alleviated the average symptom scores and immunopathology of EAE. The infiltration of immune cells, including CD4+ T and CD8+ T cells, and the generation of GM-CSF, TNF-α, and IL-17A, were remarkably reduced in the CNS from cKO mice compared with WT mice. These findings further revealed the vital role of GPX4 in the expansion and function of CD4+ T cells. Moreover, GPX4-deficient CD4+ T cells were susceptible to ferroptosis in EAE model. Overall, this study provided novel insights into therapeutic strategies targeting GPX4 in CD4+ T cells for inhibiting CNS inflammation and treating MS.
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Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Ratones , Animales , Encefalomielitis Autoinmune Experimental/metabolismo , Linfocitos T CD8-positivos , Sistema Nervioso Central/metabolismo , Esclerosis Múltiple/patología , Linfocitos T CD4-Positivos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.
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COVID-19 , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , COVID-19/terapia , Oxígeno/uso terapéutico , Hidrógeno/uso terapéuticoRESUMEN
Highly educated immigrants are part of the growing population of immigrants who are impacted by the increasingly hostile migration policies in the U.S. This qualitative study used a phenomenological approach and inductive reasoning to explore the possible impacts of migration integration policies as social determinants of health among this group. Data was collected through 31 semi-structured interviewees with highly educated immigrants who had an intention and interest to stay in the U.S. at the time of the interview. Data were analyzed using reflexive thematic analysis and four main themes emerged: (1) a life overshadowed by silent worries, (2) living through uncertainties and forced decisions as the result of migration integration policies, (3) complexities and challenges of living on a work visa, and (4) shared recommendations by interviewees. Documented narratives as part of this study suggest high rates of stress and anxiety as well as negative mental and physical health outcomes among the participants. Results also suggest high levels of internalized vulnerabilities. Participants shared that migration policies can be enhanced in the U.S. to support highly educated immigrants' growth by creating a better and more transparent communication system, replacing random review processes for applications with systematic procedures, creating expedited pathways to citizenship based on merit, and granting access to work as a basic human right.
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Emigrantes e Inmigrantes , Determinantes Sociales de la Salud , Humanos , Estados Unidos/epidemiología , Política Pública , Factores Sociales , AnsiedadRESUMEN
Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage.
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Lesión Pulmonar , Material Particulado , Humanos , Material Particulado/efectos adversos , Ácido Araquidónico/metabolismo , Lesión Pulmonar/inducido químicamente , Células Epiteliales/metabolismo , Metabolismo de los LípidosRESUMEN
A few families of transposable elements (TEs) have been shown to evolve into cis-regulatory elements (CREs). Here, to extend these studies to all classes of TEs in the human genome, we identified widespread enhancer-like repeats (ELRs) and find that ELRs reliably mark cell identities, are enriched for lineage-specific master transcription factor binding sites, and are mostly primate-specific. In particular, elements of MIR and L2 TE families whose abundance co-evolved across chordate genomes, are found as ELRs in most human cell types examined. MIR and L2 elements frequently share long-range intra-chromosomal interactions and binding of physically interacting transcription factors. We validated that eight L2 and nine MIR elements function as enhancers in reporter assays, and among 20 MIR-L2 pairings, one MIR repressed and one boosted the enhancer activity of L2 elements. Our results reveal a previously unappreciated co-evolution and interaction between two TE families in shaping regulatory networks.
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Cromosomas Humanos/genética , Elementos Transponibles de ADN , Elementos de Facilitación Genéticos , Redes Reguladoras de Genes , Genoma Humano , Células HeLa , Humanos , Células K562RESUMEN
To improve the identification and subsequent intervention of COVID-19 patients at risk for ICU admission, we constructed COVID-19 severity prediction models using logistic regression and artificial neural network (ANN) analysis and compared them with the four existing scoring systems (PSI, CURB-65, SMARTCOP, and MuLBSTA). In this prospective multi-center study, 296 patients with COVID-19 pneumonia were enrolled and split into the General-Ward-Care group (N = 238) and the ICU-Admission group (N = 58). The PSI model (AUC = 0.861) had the best results among the existing four scoring systems, followed by SMARTCOP (AUC = 0.770), motified-MuLBSTA (AUC = 0.761), and CURB-65 (AUC = 0.712). Data from 197 patients (training set) were analyzed for modeling. The beta coefficients from logistic regression were used to develop a severity prediction model and risk score calculator. The final model (NLHA2) included five covariates (consumes alcohol, neutrophil count, lymphocyte count, hemoglobin, and AKP). The NLHA2 model (training: AUC = 0.959; testing: AUC = 0.857) had similar results to the PSI model, but with fewer variable items. ANN analysis was used to build another complex model, which had higher accuracy (training: AUC = 1.000; testing: AUC = 0.907). Discrimination and calibration were further verified through bootstrapping (2000 replicates), Hosmer-Lemeshow goodness of fit testing, and Brier score calculation. In conclusion, the PSI model is the best existing system for predicting ICU admission among COVID-19 patients, while two newly-designed models (NLHA2 and ANN) performed better than PSI, and will provide a new approach for the development of prognostic evaluation system in a novel respiratory viral epidemic.
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COVID-19 , Infecciones Comunitarias Adquiridas , COVID-19/diagnóstico , Infecciones Comunitarias Adquiridas/epidemiología , Humanos , Redes Neurales de la Computación , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Nanoparticles exhibit unique properties due to their surface effects and small size, and their behavior at high pressures has attracted widespread attention in recent years. Herein, a series of in situ high-pressure X-ray diffraction measurements with a synchrotron radiation source and Raman scattering have been performed on HfO2 nanocrystals (NC-HfO2) with different grain sizes using a symmetric diamond anvil cell at ambient temperature. The experimental data reveal that the structural stability, phase transition behavior, and equation of state for HfO2 have an interesting size effect under high pressure. NC-HfO2 quenched to normal pressure is characterized by transmission electron microscopy to determine the changing behavior of grain size during phase transition. We found that the rotation of the nanocrystalline HfO2 grains causes a large strain, resulting in the retention of part of an orthorhombic I (OI) phase in the sample quenched to atmospheric pressure. Furthermore, the physical mechanism of the phase transition of NC-HfO2 under high pressure can be well explained by the first-principles calculations. The calculations demonstrate that NC-HfO2 has a strong surface effect, that is, the surface energy and surface stress can stabilize the structures. These studies may offer new insights into the understanding of the physical behavior of nanocrystal materials under high pressure and provide practical guidance for their realization in industrial applications.
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Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The m6A methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the m6A methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated m6A peaks within 1879 genes and 1278 differentially hypomethylated m6A peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four m6A-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the m6A-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.
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Epigenoma , Material Particulado , Animales , Pulmón , Ratones , Material Particulado/metabolismo , ARN/genética , TranscriptomaRESUMEN
Acute exacerbation (AE) is the main cause of increased disability and mortality for patients with Chronic Obstructive Pulmonary Disease (COPD). Short-term re-exacerbation after discharge is common for in-hospital patients with AECOPD. Thus, we aimed to design a scoring system to effectively predict the 30-day re-exacerbation using simple and easily accessible variables. We retrospectively enrolled 686 cases hospitalized for AECOPD in two Chinese hospitals from 2005 to 2017. A variety of parameters were collected like demographics, clinical manifestations and treatments in stable and AE period. The optimal subset of covariates in the multivariate logistic analysis was identified by the smallest Akaike Information Criterion (AIC) and was further used to develop a practical and reliable nomogram to predict the 30-day re-exacerbation. The efficacy of the nomogram was internally validated by concordance index (C-index) and a calibration plot. The incidence of 30-day re-exacerbation was 15.8%. Based on the smallest AIC, eight easily-accessible parameters were included in the nomogram, including sex, COPD assessment test (CAT) scores, AE with respiratory failure in the previous year, new purulent sputum, new cardiovascular events, combined antibiotic therapy, theophylline therapy for AE and ICU admission. Our nomogram revealed good discriminative ability with the C-index of 0.702. The calibration curve showed good agreement between nomogram-predicted probability and actual observation. Incorporating eight common variables, a nomogram for 30-day re-exacerbation after discharge with high predictive performance was constructed for patients with AECOPD, which was helpful in predicting individualized risk of re-exacerbation and offering individualized post-discharge support.
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Reglas de Decisión Clínica , Hospitalización , Nomogramas , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The highly sensitive optical detection of oxygen including dissolved oxygen (DO) is of great interest in various applications. We devised a novel room-temperature-phosphorescence (RTP)-based oxygen detection platform by constructing core-shell nanoparticles with water-soluble polymethyloxazoline shells and oxygen-permeable polystyrene cores crosslinked with metal-free purely organic phosphors. The resulting nanoparticles show a very high sensitivity for DO with a limit of detection (LOD) of 60â nm and can be readily used for oxygen quantification in aqueous environments as well as the gaseous phase.
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The practice of family separation as a mechanism of oppression has a deep-rooted history in the U.S., manifesting in diverse contexts, including punitive migration policies. This systematic review aimed to provide a rigorous and updated synthesis of the research on family separation as a result of migration policies and its impacts on immigrants' mental health while making a distinction between forced family separation, family separation by constrained choices, and living with the fear of family separation. We systematically searched four bibliographic databases using keywords related to family separation, migration, transnational families, and mental health for peer-reviewed studies published in English on or before January 1st, 2022. Results of the review indicate that family separation or fear of it may result in depression, anxiety, behavioral and emotional issues, sleep disturbances, and stress or distress in affected children. Similarly, impacted parents or caregivers might experience stress or distress, depression, anxiety, and sleep disturbances. Findings call for migration policy changes prioritizing family unity and comprehensive mental health interventions to respond to the pervasive consequences of family separation or fear thereof among immigrants in the U.S.
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Emigrantes e Inmigrantes , Separación Familiar , Humanos , Estados Unidos , Emigrantes e Inmigrantes/psicología , Emigrantes e Inmigrantes/estadística & datos numéricos , Salud Mental , Emigración e Inmigración/legislación & jurisprudencia , Ansiedad/psicologíaRESUMEN
In this work, a colorimetric aptasensor based on magnetic beads (MBs), gold nanoparticles (AuNPs) and Horseradish Peroxidase (HRP) was prepared for the detection of mucin 1 (MUC1). Complementary DNA of the MUC1 aptamer (Apt) immobilized on the MBs was combined with the prepared AuNPs-Apt-HRP complex (AuNPs@Apt-HRP). In the presence of MUC1, it specifically bound to Apt, resulting in the detachment of gold nanoparticles from the MBs. After magnetic separation, AuNPs@Apt-HRP was separated into the supernatant and reacted with 3,3',5,5'-Tetramethylbenzidine (TMB) to produce color reaction from colorless to blue. The linear range of MUC1 was from 75 to 500 µg/mL (R2 = 0.9878), and the detection limit was 41.95 µg/mL. The recovery rate of MUC1 in human serum was 99.18 %â¼101.15 %. This method is simple and convenient. Moreover, it does not require complex and expensive equipment for detection of MUC1. It provides value for the development of MUC1 colorimetric sensors and a promising strategy for the determination of MUC1 in clinical diagnosis.
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Aptámeros de Nucleótidos , Bencidinas , Técnicas Biosensibles , Colorimetría , Oro , Límite de Detección , Nanopartículas del Metal , Mucina-1 , Mucina-1/análisis , Mucina-1/sangre , Colorimetría/métodos , Oro/química , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química , Humanos , Técnicas Biosensibles/métodos , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismoRESUMEN
BACKGROUND: Allergic asthma has been regarded as an inflammatory disease mediated by type 2 immunity. The treatment of progressive forms of asthma remains unsatisfactory despite substantial progress in drug development. Lentinan (LTN), a specific polysaccharide derived from Lentinus edodes, exhibits anti-inflammatory and immunomodulatory functions. Nevertheless, the effect and underlying mechanisms of Lentinan on asthma remain unclear. PURPOSE: This research investigated the regulatory role of Lentinan on allergic airway inflammation and epithelial barrier dysfunction in HDM (house dust mite)-induced asthma. STUDY DESIGN: HDM-induced C57BL/6 mice received different dosages of Lentinan through intraperitoneal injections, to observe the effect of Lentinan against allergic airway inflammation and epithelial barrier dysfunction in asthma. METHODS: Mice were intranasally administered HDM extract solution on days 0, 1, 2 and on days 8 to 12, establishing the allergic asthma model. On days 8 to 12, mice were intraperitoneally administered varying doses of Lentinan (5/10/20mg/kg) 1h before HDM challenge. On day 14, samples were harvested for analysis. Cell counting, flow cytometry, ELISA, HE and PAS staining, IF staining, western blotting, RT-PCR, and bioinformatic analysis were conducted to delve into the underlying functions and mechanisms of Lentinan in asthma. RESULTS: Our study revealed that the treatment of Lentinan significantly ameliorated allergic airway inflammation and improved epithelial barrier dysfunction in experimental mice. Following Lentinan treatment, there was a significant reduction in eosinophil counts, accompanied by a diminished presence of type 2 cytokines. Reversal of epithelial barrier dysfunction after treatment was also observed. The therapeutic mechanism involved suppression of the PI3K/AKT/ NF-κB pathway. CONCLUSION: Our research illuminated the protective role of Lentinan in allergic airway inflammation and impaired epithelial barrier, suggesting LTN could be an innovative and promising candidate for asthma treatment.