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Numerous microRNAs and their target mRNAs are coexpressed across diverse cell types. However, it is unknown whether they are regulated in a manner independent of or dependent on cellular context. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets through differential iCLIP, mRNA quantification with RNA-seq, and 3' untranslated region (UTR)-usage analysis with poly(A)-seq in macrophages, dendritic cells, and T and B lymphocytes either sufficient or deficient in activated miR-155, we identified numerous targets differentially bound by miR-155. Whereas alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in most cases, identical 3'-UTR isoforms were differentially regulated across cell types, thus suggesting ApA-independent and cellular-context-dependent miR-155-mediated gene regulation. Our study provides comprehensive maps of miR-155 regulatory networks and offers a valuable resource for dissecting context-dependent and context-independent miRNA-mediated gene regulation in key immune cell types.
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Linfócitos B/imunologia , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Macrófagos/imunologia , MicroRNAs/imunologia , Linfócitos T/imunologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans1-3. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state4-6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods.
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Astrócitos/patologia , Linfócitos/patologia , Microglia/patologia , Esclerose Múltipla/patologia , Animais , Encéfalo/patologia , Complemento C1q/antagonistas & inibidores , Complemento C1q/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Inflamação/patologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , RNA-Seq , Transcriptoma , Substância Branca/patologiaRESUMO
Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK- ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK- ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK- ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.
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Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Interleucinas/metabolismoRESUMO
All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.
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The poor reversibility and stability of Zn metal anode (ZMA) caused by uncontrolled Zn deposition behaviors and serious side reactions severely impeded the practical application of aqueous Zn metal battery. Herein, a liquid-dynamic and self-adaptive protective layer (LSPL) was constructed on the ZMA surface for inhibiting dendrites and by-products formation. Interestingly, the outer LSPL consists of liquid perfluoropolyether (PFPE), which can dynamically adapt volume change during repeat cycling and inhibit side reactions. Moreover, it can also decrease the de-solvation energy barrier of Zn2+ by strong interaction between C-F bond and foreign Zn2+ , improving Zn2+ transport kinetics. For the LSPL inner region, in-situ formed ZnF2 through the spontaneous chemical reaction between metallic Zn and part PFPE can establish an unimpeded Zn2+ migration pathway for accelerating ion transfer, thereby restricting Zn dendrites formation. Consequently, the LSPL-modified ZMA enables reversible Zn deposition/dissolution up to 2000 h at 1 mA cm-2 and high coulombic efficiency of 99.8% at 4 mA cm-2 . Meanwhile, LSPL@Zn||NH4 V4 O10 full cells deliver an ultralong cycling lifespan of 100 00 cycles with 0.0056% per cycle decay rate at 10 A g-1 . This self-adaptive layer provides a new strategy to improve the interface stability for next-generation aqueous Zn battery.
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Hirudins, natural sulfo(glyco)proteins, are clinical anticoagulants that directly inhibit thrombin, a key coagulation factor. Their potent thrombin inhibition primarily results from antagonistic interactions with both the catalytic and non-catalytic sites of thrombin. Hirudins often feature sulfate moieties on Tyr residues in their anionic C-terminus region, enabling strong interactions with thrombin exosite-I and effectively blocking its engagement with fibrinogen. Although sulfotyrosines have been identified in various hirudin variants, the precise relationship between sulfotyrosine and the number of negatively charged amino acids within the anionic-rich C-terminus peptide domain for the binding of thrombin has remained elusive. By using Fmoc-SPPS, hirudin dodecapeptides homologous to the C-terminus of hirudin variants from various leech species were successfully synthesized, and the effect of sulfotyrosine and the number of negatively charged amino acids on hirudin-thrombin interactions was investigated. Our findings did not reveal any synergistic effect between an increasing number of sulfotyrosines or negatively charged amino acids and their inhibitory activity on thrombin or fibrinolysis in the assays, despite a higher binding level toward thrombin in the sulfated dodecapeptide Hnip_Hirudin was observed in SPR analysis.
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Hirudinas , Trombina , Tirosina/análogos & derivados , Hirudinas/farmacologia , Hirudinas/química , Hirudinas/metabolismo , Aminoácidos , Peptídeos/farmacologia , Sítios de LigaçãoRESUMO
BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Idoso , Análise de Sobrevida , Estimativa de Kaplan-Meier , Reprodutibilidade dos Testes , Quinolinas/uso terapêutico , Compostos de FenilureiaRESUMO
BACKGROUND AND AIMS: HCC is an aggressive disease with poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. This study aims to identify molecular players specific to CD133 + HCC to better design drugs that can precisely interfere with cancer stem cells but not normal stem cell function. APPROACH AND RESULTS: Transcriptome profiling comparison of epithelial-specific "normal" CD133 + cells isolated from fetal and regenerating liver against "HCC" CD133 + cells isolated from proto-oncogene-driven and inflammation-associated HCC revealed preferential overexpression of SERPINA12 in HCC but not fetal and regenerating liver CD133 + cells. SERPINA12 upregulation in HCC is tightly associated with aggressive clinical and stemness features, including survival, tumor stage, cirrhosis, and stemness signatures. Enrichment of SERPINA12 in HCC is mediated by promoter binding of the well-recognized ß-catenin effector TCF7L2 to drive SERPINA12 transcriptional activity. Functional characterization identified a unique and novel role of endogenous SERPINA12 in promoting self-renewal, therapy resistance, and metastatic abilities. Mechanistically, SERPINA12 functioned through binding to GRP78, resulting in a hyperactivated AKT/GSK3ß/ß-catenin signaling cascade, forming a positive feed-forward loop. Intravenous administration of rAAV8-shSERPINA12 sensitized HCC cells to sorafenib and impeded the cancer stem cell subset in an immunocompetent HCC mouse model. CONCLUSIONS: Collectively, our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133 + cells and is a key contributor to HCC initiation and progression by driving an AKT/ß-catenin feed-forward loop.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/metabolismo , Proliferação de CélulasRESUMO
MicroRNA (miRNA)-dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target (SOCS1) to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection, some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is dependent on cell type and biological context.
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Linfócitos T CD8-Positivos/imunologia , Células Matadoras Naturais/imunologia , MicroRNAs/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Linfócitos T Reguladores/imunologia , Regiões 3' não Traduzidas/genética , Animais , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Perfilação da Expressão Gênica , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Células Matadoras Naturais/transplante , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muromegalovirus/imunologia , Mutação , RNA Mensageiro/genética , Proteína 1 Supressora da Sinalização de CitocinaRESUMO
PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.
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Neoplasias Pulmonares , Testes Psicológicos , Resiliência Psicológica , Transtornos do Sono-Vigília , Humanos , Feminino , Qualidade do Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologiaRESUMO
The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.
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BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.
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Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/complicações , Nomogramas , Estudos Retrospectivos , Cirrose Hepática/diagnóstico por imagem , Curva ROCRESUMO
PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.
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Azoospermia , Infertilidade Masculina , Oligospermia , Humanos , Masculino , Feminino , Azoospermia/epidemiologia , Azoospermia/genética , Estudos Retrospectivos , Deleção Cromossômica , Infertilidade Masculina/genética , Cromossomos Humanos Y/genética , China/epidemiologia , Oligospermia/genéticaRESUMO
Esophageal cancer (EC) is a common digestive malignancy that ranks sixth in cancer deaths, with a 5-year survival rate of 15%-25%. As a result, reliable prognostic biomarkers are required to accurately predict the prognosis of EC. T-cell exhaustion (TEX) is associated with poorer prognosis and immune infiltration in EC. In this study, nine risk genes were finally screened to constitute the prognostic model using least absolute shrinkage and selection operator analysis. Patients were divided into two groups based on the expression of the TEX-related genes: high-risk group and low-risk group. The expression of TEX-related genes differed significantly between the two groups. The findings revealed that the risk model developed was highly related to the clinical prognosis and amount of immune cell infiltration in EC patients. It was also significantly correlated with the therapeutic sensitivity of multiple chemotherapeutic agents in EC patients. Subsequently, we successfully constructed drug-resistant cell lines KYSE480/CDDP-R and KYSE180/CDDP-R to verify the correlation between PD-1 and drug resistance in EC. Then, we examined the mRNA and protein expression levels of PD-1 in parental and drug-resistant cells using qPCR and WB. It was found that the expression level of PD-1 was significantly increased in the plasma red of drug-resistant cells. Next, we knocked down PD-1 in drug-resistant cells and found that the resistance of EC cells to CDDP was significantly reduced. And the proportion of apoptotic cells in cells treated with 6 µM CDDP for 24 h was significantly in increase. The TEX-based risk model achieved good prediction results for prognosis prediction in EC patients. And it was also significantly associated with the level of immune cell infiltration and drug therapy sensitivity of EC patients. Additionally, the downregulation of PD-1 may be associated with increased drug sensitivity in EC and enhanced T-cell infiltration. The high-risk group had lower TIDE scores, indicating that the high-risk group benefits more after receiving immunotherapy. Thus, the TEX-based risk model can be used as a novel tumor prognostic biomarker.
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Neoplasias Esofágicas , Microambiente Tumoral , Humanos , Prognóstico , Receptor de Morte Celular Programada 1 , Exaustão das Células T , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Imunoterapia , AlgoritmosRESUMO
In urban areas like Chicago, daily life extends above ground level due to the prevalence of high-rise buildings where residents and commuters live and work. This study examines the variation in fine particulate matter (PM2.5) concentrations across building stories. PM2.5 levels were measured using PurpleAir sensors, installed between 8 April and 7 May 2023, on floors one, four, six, and nine of an office building in Chicago. Additionally, data were collected from a public outdoor PurpleAir sensor on the fourteenth floor of a condominium located 800 m away. The results show that outdoor PM2.5 concentrations peak at 14 m height, and then decline by 0.11 µg/m3 per meter elevation, especially noticeable from midnight to 8 a.m. under stable atmospheric conditions. Indoor PM2.5 concentrations increase steadily by 0.02 µg/m3 per meter elevation, particularly during peak work hours, likely caused by greater infiltration rates at higher floors. Both outdoor and indoor concentrations peak around noon. We find that indoor and outdoor PM2.5 are positively correlated, with indoor levels consistently remaining lower than outside levels. These findings align with previous research suggesting decreasing outdoor air pollution concentrations with increasing height. The study informs decision-making by community members and policymakers regarding air pollution exposure in urban settings.
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Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Material Particulado , Material Particulado/análise , Chicago , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/análiseRESUMO
BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.
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Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/psicologia , Modelos LogísticosRESUMO
It remains a great challenge to design and manufacture battery-type supercapacitors with satisfactory flexibility, appropriate mechanical property, and high energy density under high power density. Herein, a concept of porous engineering is proposed to simply prepare two-layered bimetallic heterojunction with porous structures. This concept is successfully applied in fabrication of flexible electrode based on CuO-Co(OH)2 lamella on Cu-plated carbon cloth (named as CPCC@CuO@Co(OH)2 ). The unique structure brings the electrode a high specific capacity of 3620 mF cm-2 at 2 mA cm-2 and appropriate mechanical properties with Young's modulus of 302.0 MPa. Density functional theory calculations show that porous heterojunction provides a higher intensity of electron state density near the Fermi level (E-Ef = 0 eV), leading to a highly conductive CPCC@CuO@Co(OH)2 electrode with both efficient charge transport and rapid ion diffusion. Notably, the supercapacitor assembled from CPCC@CuO@Co(OH)2 //CC@AC shows high energy density of 127.7 W h kg-1 at 750.0 W kg-1 , remarkable cycling performance (95.53% capacity maintaining after 10 000 cycles), and desired mechanical flexibility. The methodology and results in this work will accelerate the transformative developments of flexible energy storage devices in practical applications.
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Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to decompose in cycling. Herein, in order to guide the homogeneous deposition of Li+ , carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M-CPDs) and hydrothermal (H-CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic-N, pyrrolic-N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li+ through electrostatic interaction effectively guide the uniform Li dispersion and limit the "tip effect" and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li+ in the electrolyte is formed, which induces faster Li+ diffusion/transfer. As expected, H-CPDs achieve the ultra-even Li+ transfer. The corresponding Li//LiFePO4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M-CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices.
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The dendrite growth and parasitic reactions that occur on Zn metal anode (ZMA)/electrolyte interface hinder the development of aqueous zinc ion batteries (AZIBs) in next-generation renewable energy storage systems. Fortunately, reconstructing the inner Helmholtz layer (IHL) by introducing an electrolyte additive, is viewed as one of the most promising strategies to harvest the stable ZMA. Herein, (4-chloro-3-nitrophenyl) (pyridin-4-yl) methanone (CNPM) with quadruple functional groups is introduced into the ZnSO4 electrolyte to reshape the interface between ZMA and electrolyte and change the solvation structure of Zn2+ . Density functional theory (DFT) calculations manifest that the âCâO, âCl, âCâNâ, and âNO2 functional groups of CNPM interact with metallic Zn simultaneously and adsorb on the ZMA surface in a parallel arrangement manner, thus forming a water-poor IHL and creating well-arranged ion transportation channels. Furthermore, theoretical calculations and experimental results demonstrate that CNPM absorbed on the Zn anode surface can serve as zincophilic sites for inducing uniform Zn deposition along the (002) plane. Benefiting from the synergistic effect of these functions, the dendrite growth and parasitic reactions are suppressed significantly. As a result, ZMA exhibits a long cycle life (2900 h) and high coulombic efficiency (CE) (500 cycles) in the ZnSO4 +CNPM electrolyte.
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Despite being one of the most promising materials in anode materials, molybdenum sulfide (MoS2 ) encounters certain obstacles, such as inadequate cycle stability, low conductivity, and unsatisfactory charge-discharge (CD) rate performance. In this study, a novel approach is employed to address the drawbacks of MoS2 . Carbon polymer dots (CPDs) are incorporated to prepare three-dimensional (3D) nanoflower-like spheres of MoS2 @CPDs through the self-assembly of MoS2 2D nanosheets, followed by annealing at 700 °C. The CPDs play a main role in the creation of the nanoflower-like spheres and also mitigate the MoS2 nanosheet limitations. The nanoflower-like spheres minimize volume changes during cycling and improve the rate performance, leading to exceptional rate performance and cycling stability in both Lithium-ion and Sodium-ion batteries (LIBs and SIBs). The optimized MoS2 @CPDs-2 electrode achieves a superb capacity of 583.4 mA h g-1 at high current density (5 A g-1 ) after 1000 cycles in LIBs, and the capacity remaining of 302.8 mA h g-1 after 500 cycles at 5 A g-1 in SIBs. Additionally, the full cell of LIBs/SIBs exhibits high capacity and good cycling stability, demonstrating its potential for practical application in fast-charging and high-energy storage.