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Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.
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Ferroptosis/fisiología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/farmacología , Células T Auxiliares Foliculares/fisiología , Adolescente , Adulto , Animales , Supervivencia Celular/inmunología , Niño , Femenino , Centro Germinal/citología , Centro Germinal/inmunología , Homeostasis/efectos de los fármacos , Homeostasis/genética , Humanos , Inmunidad Humoral/inmunología , Vacunas contra la Influenza/inmunología , Peroxidación de Lípido/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/fisiología , Ovalbúmina , Células T Auxiliares Foliculares/inmunología , Vacunación , Adulto JovenRESUMEN
Unambiguous targeting of cellular structures for in situ cryo-electron microscopy in the heterogeneous, dense and compacted environment of the cytoplasm remains challenging. Here, we have developed a cryogenic correlative light and electron microscopy (cryo-CLEM) workflow that utilizes thin cells grown on a mechanically defined substratum for rapid analysis of organelles and macromolecular complexes by cryo-electron tomography (cryo-ET). We coupled these advancements with optogenetics to redistribute perinuclear-localised organelles to the cell periphery, allowing visualisation of organelles that would otherwise be positioned in cellular regions too thick for cryo-ET. This reliable and robust workflow allows for fast in situ analyses without the requirement for cryo-focused ion beam milling. Using this protocol, cells can be frozen, imaged by cryo-fluorescence microscopy and be ready for batch cryo-ET within a day.
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Microscopía por Crioelectrón , Optogenética , Orgánulos , Microscopía por Crioelectrón/métodos , Orgánulos/ultraestructura , Optogenética/métodos , Tomografía con Microscopio Electrónico/métodos , Humanos , Microscopía Fluorescente/métodosRESUMEN
Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that support germinal centers in producing high-affinity antibody-secreting and memory B cells in mammals and birds. Therefore, mechanisms have evolved to control the life and death of TFH cells for balanced humoral immunity. Recent studies have collectively revealed at least two programmed cell death pathways, ferroptosis and pyroptosis, which govern TFH cell survival under diverse physiopathological conditions including immunization, infection, gut homeostasis, and autoimmunity. We review major recent advances in our understanding of the context-dependent regulation of TFH cell survival via cell death pathways that are closely connected with cellular metabolism. Such knowledge might be applied to inform new strategies aimed at modulating humoral immunity, potentially including enhancement of vaccine efficacies.
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Centro Germinal , Células T Auxiliares Foliculares , Animales , Autoinmunidad , Diferenciación Celular , Humanos , Inmunidad Humoral , Inmunización , Mamíferos , Linfocitos T Colaboradores-InductoresRESUMEN
BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.
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Pólipos Nasales , Estructuras Linfoides Terciarias , Humanos , Linfocitos T Reguladores/patología , Linfocitos T Colaboradores-Inductores/patología , Antígeno CTLA-4/metabolismo , Receptores de Calcitriol/metabolismo , Pólipos Nasales/patología , Estructuras Linfoides Terciarias/patología , Inmunoglobulinas/metabolismo , Vitamina D/metabolismoRESUMEN
Nitrate (NO3-) in wastewater poses a serious threat to human health and the ecological environment. The electrocatalytic NO3- reduction to ammonia (NH3) reaction (NO3-RR) emerges as a promising carbon-free energy route for enabling NO3- removal and sustainable NH3 synthesis. However, it remains a challenge to achieve high Faraday efficiencies at a wide potential window due to the complex multiple-electron reduction process. Herein, spatially separated dual-metal tandem electrocatalysts made of a nitrogen-doped ordered mesoporous carbon support with ultrasmall and high-content Cu nanoparticles encapsulated inside and large and low-content Ru nanoparticles dispersed on the external surface (denoted as Ru/Cu@NOMC) are designed. In electrocatalytic NO3-RR, the Cu sites can quickly convert NO3- to adsorbed NO2- (*NO2-), while the Ru sites can efficiently produce active hydrogen (*H) to enhance the kinetics of converting *NO2- to NH3 on the Cu sites. Due to the synergistic effect between the Cu and Ru sites, Ru/Cu@NOMC exhibits a maximum NH3 Faradaic efficiency (FENH3) of approximately 100% at -0.1 V vs reversible hydrogen electrode (RHE) and a high NH3 yield rate of 1267 mmol gcat-1 h-1 at -0.5 V vs RHE. Finite element method (FEM) simulation and electrochemical in situ Raman spectroscopy revealed that the mesoporous framework can enhance the intermediate concentration due to the in situ confinement effect. Thanks to the Cu-Ru synergistic effect and the mesopore confinement effect, a wide potential window of approximately 500 mV for FENH3 over 90% and a superior stability for NH3 production over 156 h can be achieved on the Ru/Cu@NOMC catalyst.
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BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.
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Biomarcadores , Desensibilización Inmunológica , Pyroglyphidae , Rinitis Alérgica , Humanos , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Masculino , Desensibilización Inmunológica/métodos , Animales , Femenino , Adulto , Pyroglyphidae/inmunología , Resultado del Tratamiento , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Adulto Joven , Alérgenos/inmunología , Alérgenos/administración & dosificación , Antígenos Dermatofagoides/inmunología , Inyecciones Subcutáneas , Adolescente , PronósticoRESUMEN
BACKGROUND: Environmental modification of genetic information (epigenetics) is often invoked to explain interindividual differences in the phenotype of schizophrenia. In clinical practice, such variability is most prominent in the symptom profile and the treatment response. Epigenetic regulation of immune function is of particular interest, given the therapeutic relevance of this mechanism in schizophrenia. METHODS: We analyzed the DNA methylation data of immune-relevant genes in patients with schizophrenia whose disease duration was less than 3 years, with previous lifetime antipsychotic treatment of no more than 2 weeks total. RESULTS: A total of 441 patients met the inclusion criteria. Core symptoms were consistently associated with 206 methylation positions, many of which had previously been implicated in inflammatory responses. Of these, 24 methylation positions were located either in regulatory regions or near the CpG islands of 20 genes, including the SRC gene, which is a key player in glutamatergic signalling. These symptom-associated immune genes were enriched in neuronal development functions, such as neuronal migration and glutamatergic synapse. Compared with using only clinical information (including scores on the Positive and Negative Syndrome Scale), integrating methylation data into the model significantly improved the predictive ability (as indicated by area under the curve) for response to 8 weeks of antipsychotic treatment. LIMITATIONS: We focused on a small number of methylation probes (immune-centred search) and lacked nutritional data and direct brain-based measures. CONCLUSION: Epigenetic modifications of the immune system are associated with symptom severity at onset and subsequent treatment response in schizophrenia.
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Antipsicóticos , Esquizofrenia , Humanos , Epigénesis Genética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Antipsicóticos/uso terapéutico , Metilación de ADN , Islas de CpG , Sistema InmunológicoRESUMEN
Despite the clinical success of monoclonal and bispecific antibodies, there are still limitations in the therapeutic effect of malignant tumours, such as low response rate, treatment resistance, and so on, inspiring the exploration of trispecific antibodies (TsAbs). TsAbs further improve the safety and efficacy and has great clinical potential through three targets combination and formats optimization. This article reviews the development history and the target combination features of TsAbs. Although there are still great challenges in the clinical application of TsAbs, it is undeniable that TsAbs may be a breakthrough in the development of antibody drugs.
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Anticuerpos Biespecíficos , Neoplasias , Humanos , Inmunoterapia , Anticuerpos Biespecíficos/uso terapéutico , Neoplasias/terapiaRESUMEN
Polymerization-induced microphase separation (PIMS) is a versatile technique for producing nanostructured materials. In previous PIMS studies, the predominant approach involved employing homopolymers as macromolecular chain transfer agents (macroCTAs) to mediate the formation of nanostructured materials. In this article, the use of AB diblock copolymers as macroCTAs to design PIMS systems for 3D printing of nanostructured materials is investigated. Specifically, the influence of diblock copolymer composition and block sequence on the resulting nanostructures, and their subsequent impact on bulk properties is systematically investigated. Through careful manipulation of the A/B block ratios, the morphology and size of the nanodomains are successfully controlled. Remarkably, the sequence of A and B blocks significantly affects the microphase separation process, resulting in distinct morphologies. The effect can be attributed to changes in the interaction parameters (χAB , χBC , χAC ) between the different block segments. Furthermore, the block sequence and composition exert profound influence on the thermomechanical, tensile, and swelling properties of 3D printed nanostructured materials. By leveraging this knowledge, it becomes possible to design advanced 3D printable materials with tailored properties, opening new avenues for material engineering.
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BACKGROUND: Local immunoglobulin hyperproduction is observed in nasal polyps (NPs) with and without ectopic lymphoid tissues (eLTs). OBJECTIVE: Our aim was to identify the T-cell subsets involved in local immunoglobulin production independent of eLTs in NPs. METHODS: The localization, abundance, and phenotype of CD4+ T-cell subsets were studied by immunofluorescence, flow cytometry, and single-cell RNA sequencing. Purified nasal T-cell subsets were cultured with autologous peripheral naive B cells to explore their function. Programmed death ligand 1 and programmed death ligand 2 expression in NPs was investigated by immunofluorescence staining and flow cytometry. RESULTS: Accumulation of PD-1highCXCR5-CD4+ T cells outside lymphoid aggregates was found in NPs. Nasal PD-1highCXCR5-CD4+ T cells were characterized by a unique phenotype that was related to B-cell help and tissue residency and distinct from PD-1-/intCXCR5- and CXCR5+ CD4+ T cells in NPs as well as PD-1highCXCR5highCD4+ follicular helper T cells in tonsils. Compared with the frequencies of PD-1highCXCR5-CD4+ T cells and their IFN-γ+, IL-17A+, and IL-21+ subsets in the control inferior turbinate tissues, the frequencies of these cells and their subsets were increased in both eosinophilic and noneosinophilic NPs, whereas the frequencies of the IL-4+ and IL-4+IL-21+ subsets were increased only in eosinophilic NPs. Nasal PD-1highCXCR5-CD4+ T cells induced immunoglobulin production from B cells in a potency comparable to that induced by tonsillar follicular helper T cells. PD-1highCXCR5-CD4+ T-cell frequencies were correlated with IgE levels in eosinophilic NPs. PD-L1 and PD-L2 suppressed the function of PD-1highCXCR5-CD4+ T cells, and their levels were reduced in NPs. PD-1highCXCR5-CD4+ T-cell abundance was associated with the postsurgical relapse of NPs. CONCLUSION: PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production independent of eLTs in NPs.
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Linfocitos T CD4-Positivos/inmunología , Inmunoglobulinas/biosíntesis , Pólipos Nasales/inmunología , Receptor de Muerte Celular Programada 1/análisis , Receptores CXCR5/análisis , Antígeno B7-H1/análisis , Células Cultivadas , Humanos , Interleucina-4/biosíntesis , Proteína 2 Ligando de Muerte Celular Programada 1/análisisRESUMEN
OBJECTIVES: To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. DESIGN: This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. RESULTS AND CONCLUSION: CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/diagnóstico , Rinitis/terapia , Rinitis/epidemiología , Sinusitis/diagnóstico , Sinusitis/terapia , Sinusitis/epidemiología , Inflamación , Fenotipo , Enfermedad CrónicaRESUMEN
Chronic rhinosinusitis (CRS) is a highly heterogeneous disorder exhibiting considerable epidemiological, clinical and immunopathological variations across patients with distinct ethnic backgrounds and in different geographic locations. Asian CRS patients present less eosinophilic and type 2 (T2) inflammation, but more prominent neutrophilic inflammation compared with patients in Western countries. Although several biologics targeting important elements of T2 inflammation, such as IL-4, IL-5, IL-13 and IgE, demonstrate promising benefit for Caucasian patients with recurrent nasal polyps, their efficacy in Asian patients remains poorly defined. The distinct endotypes in Asian patients warrant the identification and selection of patients who would benefit from T2 biologics in Asian countries. Additionally, developing novel treatments targeting neutrophilic, type 1, and type 3 inflammation may benefit approximately 50% of Asian CRS patients with non-T2 inflammation. In this review, we summarized and discussed recent progress in the study of Asian CRS endotypes in comparison with those in patients in Western countries, and the methods of identifying Asian patients with eosinophilic or T2 inflammation. T2 biologic treatment of Asian CRS patients, potential therapeutic candidates targeting non-T2 inflammation in Asian CRS patients and the progress on developing other T2 biologics were discussed.
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Productos Biológicos , Pólipos Nasales , Rinitis , Sinusitis , Productos Biológicos/uso terapéutico , Enfermedad Crónica , Humanos , Inflamación , Rinitis/tratamiento farmacológico , Rinitis/epidemiologíaRESUMEN
Schizophrenia is a severe neuropsychiatric disorder with core features including hallucinations, delusions, and cognition deficits. Accumulating evidence has implicated abnormal DNA methylation in the development of schizophrenia. However, the mechanisms by which DNA methylation changes alter the risk for schizophrenia remain largely unknown. We recently carried out a DNA methylome study of peripheral blood samples from 469 first-episode patients with schizophrenia and 476 age- and gender-matched healthy controls of Han Chinese origin. Genomic DNA methylation patterns were quantified using an Illumina Infinium Human MethylationEPIC BeadChip. We identified multiple differentially methylated positions (DMPs) and regions between patients and controls. The most significant DMPs were annotated to genes C17orf53, THAP1 and KCNQ4 (KV7.4), with Bonferroni-adjusted P values of [Formula: see text], [Formula: see text], and [Formula: see text], respectively. In particular, KCNQ4 encodes a voltage-gated potassium channel of the KV7 family, which is linked to neuronal excitability. The genes associated with top-ranked DMPs also included many genes involved in nervous system development, such as LIMK2 and TMOD2. Gene ontology analysis of the differentially methylated genes further identified strong enrichment of neuronal networks, including neuron projection extension, axonogenesis and neuron apoptotic process. Finally, we provided evidence that schizophrenia-associated epigenetic alterations co-localize with genetic susceptibility loci. By focusing on first-episode schizophrenia patients, our investigation lends particularly strong support for an important role of DNA methylation in schizophrenia pathogenesis unconfounded by the effects of long-term antipsychotic medication or disease progression. The observed DNA methylation aberrations in schizophrenia patients could potentially provide a valuable resource for identifying diagnostic biomarkers and developing novel therapeutic targets to benefit schizophrenia patients.
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Metilación de ADN , Esquizofrenia , Pueblo Asiatico , Células Sanguíneas , China , Islas de CpG/genética , Metilación de ADN/genética , Epigénesis Genética , Humanos , Esquizofrenia/genéticaRESUMEN
The aim of this paper is to further demonstrate the advantages and effectiveness of the constitutive formulation proposed by Huang (Huang 2014 J. Appl. Mech. 59, 902-908 (doi:10.1115/1.2894059)). In this formulation, any strain-energy function for an incompressible material can be easily generalized to include the effect of material compressibility, in which only a few material parameters and material functions to be fitted with the experimental data are required. To this end, the Ogden model for incompressible rubber-like solids is chosen as the starting point. By means of this formulation, the generalized Ogden strain-energy function, which takes into account material compressibility, can conveniently be constructed so long as its incompressible counterpart is given. The obvious advantage shown in this paper is that only a few material parameters and material functions are needed, i.e. in addition to the material parameters used in the original Ogden model for incompressible solids, only one material function depending on the volume ratio is involved to characterize the effect of compressibility. Both the material parameters in the original Ogden model and the material function suggested in this paper can be determined by fitting the experimental data for uniaxially tensile test and hydrostatic deformation test of rubbers, respectively. The present model considering compressibility is general since it can be applied to predict the stress-strain responses of rubber-like materials and porous rubbers in various loading conditions. With the present formulation, the applicable range of the celebrated Ogden model can be further broadened, which should be of practical importance for accurately describing the mechanical behaviour of rubber-like solids. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.
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The role of step sites on nanocatalysts in the electrocatalytic dechlorination reaction (ECDR) was studied using 3 Pd nanocatalysts with different densities of step sites, which decreased in the order of: tetrahexahedral Pd{310} nanocrystals (THH Pd{310} NCs) > commercial Pd nanoparticles (Pd black) > cubic Pd{100} NCs. The two well-defined Pd NCs served as model catalysts and were prepared through the electrochemical square-wave potential (SWP) method. The toxic herbicide alachlor was first employed in this study as an objective probe to determine the dechlorination performance, which was quantified by the alachlor removal (Rala), the current efficiency (CEala), and the dechlorination selectivity (Sdes). The experimental results demonstrated that the THH Pd{310} NCs with abundant step sites exhibited much higher electrocatalytic performance compared to the cubic Pd{100} NCs with terrace sites. The combination of cyclic voltammetry studies, electrochemical in situ FTIR analysis, and density functional theory (DFT) calculations revealed that the adsorbed CîO bond and generated on the step sites could lower the C-Cl bond splitting barrier, leading to a high ECDR efficiency. Other chlorinated organics with an activated carbon atom were also investigated, which revealed that the superiority of the step sites toward Cl-C bond breaking was particular to the compounds with CîO bonds. This study provides a deep understanding of high actvitiy of step sites on Pd NCs in EHDC and a strategy to improve this important environmental electrocatalysis process.
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BACKGROUND: Pharynx and larynx cancers (PLCs) are the top killer cancers in head and neck and significantly affect the quality of life of patients. A detailed study examining the disease burden and risk factors of PLCs is lacking. METHODS: Data on mortality and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The estimated annual percentage change (EAPC) of the age-standardized mortality rate was calculated using a generalized linear model with a Gaussian distribution. Mortality and DALYs were stratified according to the sociodemographic index (SDI), age, gender, and risk factors. The association between the SDI and mortality rate was measured using Spearman's correlation. RESULTS: Between 1990 and 2019, the total number of deaths due to PLCs increased by 60.7% (95% confidence intervals: 39.32 to 66.8), from 192.38 thousand in 1990 to 309.16 thousand in 2019, and the total DALYs due to PLCs increased by 49.41% (95% confidence intervals: 30.15 to 53.27), from 5.91 million in 1990 to 8.83 million in 2019. The age-standardized mortality rate declined for larynx cancer (from 2.19 in 1990 to 1.49 in 2019) and nasopharynx cancer (1.26 to 0.86) but increased slightly for other pharynx cancer (1.25 to 1.37). The death number of PLCs was significantly higher in men aged 50 to 70 years, which accounts for 46.05% and 43.83% of the total deaths in 1990 and 2019, respectively. Low and low-middle countries had the greatest age-standardized mortality rate for larynx and other pharynx cancer, while low-middle and middle countries dominated for nasopharynx cancer. The leading risk factors for PLCs were smoking and alcohol use, which account for 37.92% and 58.84% in total DALYs rate of PLCs, and the influence of risk factors was significant in men. CONCLUSION: The total number of deaths and DALYs due to PLCs increased from 1990 to 2019. Countries with relatively low SDI and middle-aged and older men had the greatest burden of PLCs. Building better health care systems in relatively low SDI countries and improving strategies of smoking and alcohol control should be a priority in health policy.
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Neoplasias Laríngeas , Neoplasias Nasofaríngeas , Neoplasias Faríngeas , Masculino , Persona de Mediana Edad , Humanos , Anciano , Faringe , Calidad de Vida , Carga Global de Enfermedades , Costo de Enfermedad , Neoplasias Faríngeas/epidemiología , Factores de RiesgoRESUMEN
AIM: To evaluate the effects of hsa-miRNA-143-3p on the cytodifferentiation of human stem cells from the apical papilla (hSCAPs) and the post-transcriptional regulation of Nuclear factor I-C (NFIC). METHODOLOGY: miRNA expression profiles in human immature permanent teeth and during hSCAP differentiation were examined. hSCAPs were treated with miR-143-3p overexpression or silencing viruses, and the proliferation and odontogenic and osteogenic differentiation of these stem cells, and the involvement of the NFIC pathway, were investigated. Luciferase reporter and NFIC mutant plasmids were used to confirm NFIC mRNA as a direct target of miR-143-3p. NFIC expression analysis in the miR-143-3p overexpressing hSCAPs was used to investigate whether miR-143-3p functioned by targeting NFIC. Student's t-test and chi-square tests were used for statistical analysis. RESULTS: miR-143-3p expression was screened by microarray profiling and was found to be significantly reduced during hSCAP differentiation (p < .05). Overexpression of miR-143-3p inhibited the mineralization of hSCAPs significantly (p < .05) and downregulated the levels of odontogenic differentiation markers (NFIC [p < .05], DSP [p < .01] and KLF4 [p < .01]), whereas silencing of miR-143-3p had the opposite effect. The luciferase reporter gene detection and bioinformatic approaches identified NFIC mRNA as a potential target of miR-143-3p. NFIC overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAPs. CONCLUSIONS: miR-143-3p maintained the stemness of hSCAPs and modulated their differentiation negatively by directly targeting NFIC. Thus, inhibition of this miRNA represents a potential strategy to promote the regeneration of damaged tooth roots.
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Diferenciación Celular , Papila Dental/citología , MicroARNs , Factores de Transcripción NFI , Células Cultivadas , Humanos , MicroARNs/genética , Factores de Transcripción NFI/genética , Osteogénesis , Células MadreRESUMEN
BACKGROUND: Currently, most postpartum posttraumatic stress disorder (PTSD) screening scales used in China are general PTSD scales which are not compiled specifically for pregnant women and thus cannot reflect the unique needs of this population. This study aimed to translate the City Birth Trauma Scale (City BiTS) into Chinese and validate its psychometric characteristics in Chinese postpartum women. METHODS: After translation, back-translation, and expert discussion, 596 mothers at 1 to 12 months postpartum filled out the questionnaires through the Internet. The reliability and validity of the translated questionnaire were tested. RESULTS: The Cronbach's α coefficient of the Chinese version of City BiTS (City BiTS-C) was 0.889, the test-retest reliability was 0.86, and the content validity was 0.93. Exploratory factor analysis extracted two factors accounted for 63.148% of the variance. The City BiTS-C had appropriate construct validity in the Chinese culture (root mean square error of approximation [RMSEA] = 0.048, <0.05; χ2 /df = 2.666, <3). The values of the incremental fit index (IFI) and the Tucker-Lewis coefficient (TLI) were 0.990 and 0.976, which identified that the model was a good fit for the data. The values of the comparative fit index (CFI) and the normed fit index (NFI) were 0.890 and 0.873, respectively. CONCLUSIONS: The City BiTS-C is a reliable and valid measure to screening and diagnosis the postpartum PTSD among new mothers who gave birth in the past year in mainland China. IMPLICATIONS: The City BiTS-C is a short, reliable, and valid instrument that measures the symptoms of postpartum PTSD, and it is recommend for clinical screening.