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DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA , Longevidade/genética , Sirtuínas/metabolismo , Sequência de Aminoácidos , Animais , Peso Corporal , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Evolução Molecular , Fibroblastos/citologia , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Humanos , Cinética , Masculino , Mutagênese , Filogenia , Roedores/classificação , Alinhamento de Sequência , Sirtuínas/química , Sirtuínas/genética , Raios UltravioletaRESUMO
Dendritic cells (DC) are currently classified as conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Through a combination of single-cell transcriptomic analysis, mass cytometry, in vivo fate mapping and in vitro clonal assays, here we show that, at the single-cell level, the priming of mouse hematopoietic progenitor cells toward the pDC lineage occurs at the common lymphoid progenitor stage, indicative of early divergence of the pDC and cDC lineages. We found the transcriptional signature of a pDC precursor stage, defined here, in the IL-7Rα+ common lymphoid progenitor population and identified Ly6D, IL-7Rα, CD81 and CD2 as key markers of pDC differentiation, which distinguish pDC precursors from cDC precursors. In conclusion, pDCs developed in the bone marrow from a Ly6DhiCD2hi lymphoid progenitor cell and differentiated independently of the myeloid cDC lineage.
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Antígenos Ly/metabolismo , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/metabolismo , Células Progenitoras Mieloides/citologia , Células Progenitoras Mieloides/metabolismo , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Citometria de Fluxo , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Camundongos , TranscriptomaRESUMO
Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1loTOXlo, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells were uncommon. Patients with tumor-infiltrating HBV-specific CD8+ Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8+ Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.
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Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Memória Imunológica/imunologia , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Antígenos de Neoplasias/imunologia , Carcinoma Hepatocelular/patologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Receptor de Morte Celular Programada 1/metabolismo , Células Tumorais CultivadasRESUMO
Immunologists are being compelled to develop new high-dimensional perspectives of cellular heterogeneity and to determine which applications best exploit the power of mass cytometry and associated multiplex approaches.
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Técnicas Citológicas/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Animais , Anticorpos Monoclonais/imunologia , Técnicas de Química Combinatória , Técnicas Citológicas/instrumentação , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Aprendizado de Máquina , Substâncias Macromoleculares/análise , Matemática , Células Mieloides/imunologia , Sensibilidade e Especificidade , Análise de Célula Única/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologiaRESUMO
While deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect in human colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both in vitro and in xenograft colon cancers. At the molecular level, we identified ATXN3 as a bona fide deubiquitinase specifically targeting Galectin-9, as ATXN3 interacted with and inhibited Galectin-9 ubiquitination. Consequently, targeted ATXN3 ablation resulted in reduced Galectin-9 protein expression, thereby diminishing Galectin-9-induced colon cancer apoptosis and cell growth arrest. The ectopic expression of Galectin-9 fully reversed the growth of ATXN3-null colon cancer in mice. Furthermore, immunohistochemistry staining revealed a significant reduction in both ATXN3 and Galectin-9 protein expression, along with a positive correlation between them in human colon cancer. Our study identifies the first Galectin-9-specific deubiquitinase and unveils a tumor-suppressive role of ATXN3 in human colon cancer.
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Adenocarcinoma , Apoptose , Ataxina-3 , Neoplasias do Colo , Galectinas , Humanos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Galectinas/metabolismo , Galectinas/genética , Animais , Ataxina-3/metabolismo , Ataxina-3/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/genética , Camundongos , Linhagem Celular Tumoral , Ubiquitinação , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas RepressorasRESUMO
The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.
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Antígenos CD , Plasmodium vivax , Proteínas de Protozoários , Receptores da Transferrina , Reticulócitos , Plasmodium vivax/metabolismo , Plasmodium vivax/genética , Reticulócitos/metabolismo , Reticulócitos/parasitologia , Humanos , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/genética , Ligação Proteica , Proteína 1 de Superfície de Merozoito/metabolismo , Proteína 1 de Superfície de Merozoito/genética , Malária Vivax/parasitologia , Malária Vivax/metabolismo , AnimaisRESUMO
Inflammation is a significant pathological manifestation of inflammatory bowel disease (IBD), yet its mechanism has remained unclear. Although WNT2B is enriched in the intestinal inflammatory tissue of IBD patients, the specific mechanism of WNT2B in the formation of intestinal inflammation remains unclear. This study was aimed to investigate whether macrophages expressing WNT2B can aggravate intestinal tissue inflammation. Samples were collected from both normal individuals and patients with IBD at multiple colon sites. Macrophages were identified using tissue immunofluorescence. IκB kinase (IKK)-interacting protein (IKIP), which interacts with WNT2B, was found by protein cross-linking and protein mass spectrometry. The expression of WNT2B, IKIP, the NF-κB pathway, and downstream molecules were analyzed. An acute colitis model of C57BL/6J mice was established using an adeno-associated virus (AAV)-mediated WNT2B knockdown system and 3% dextran sulfate sodium (DSS). The degree of intestinal inflammation in mice was assessed upon WNT2B knockdown in macrophages. Macrophages expressing WNT2B were found to be enriched in the colitis tissues of IBD patients. WNT2B in macrophages activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines. By competitively binding IKIP, WNT2B reduced the binding of IKIP to IKKß and promoted the activation of the NF-κB pathway. Using an AAV-mediated WNT2B knockdown system, WNT2B expression in intestinal macrophages was suppressed, leading to a reduction in intestinal inflammation. WNT2B activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines by competitively binding to IKIP, potentially contributing to colon inflammatory injury in IBD.
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Colite , Doenças Inflamatórias Intestinais , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Doenças Inflamatórias Intestinais/metabolismo , Colite/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Sulfato de Dextrana , Glicoproteínas/metabolismo , Proteínas Wnt/metabolismoRESUMO
Recently discovered as an intrinsic antiferromagnetic topological insulator, MnBi2Te4 has attracted tremendous research interest, as it provides an ideal platform to explore the interplay between topological and magnetic orders. MnBi2Te4 displays distinct exotic topological phases that are inextricably linked to the different magnetic structures of the material. In this study, we conducted electrical transport measurements and systematically investigated the anomalous Hall response of epitaxial MnBi2Te4 films when subjected to an external magnetic field sweep, revealing the different magnetic structures stemming from the interplay of applied fields and the material's intrinsic antiferromagnetic (AFM) ordering. Our results demonstrate that the nonsquare anomalous Hall loop is a consequence of the distinct reversal processes within individual septuple layers. These findings shed light on the intricate magnetic structures in MnBi2Te4 and related materials, offering insights into understanding their transport properties and facilitating the implementation of AFM topological electronics.
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Hepatocellular carcinoma (HCC) exhibits a high mortality rate due to its high invasion and metastatic nature, and the acidic microenvironment plays a pivotal role. Acid-sensing ion channel 1 (ASIC1) is upregulated in HCC tissues and facilitates tumor progression in a pH-dependent manner, while the specific mechanisms therein remain currently unclear. Herein, we aimed to investigate the underlying mechanisms by which ASIC1 contributes to the development of HCC. Using bioinformatics analysis, we found a significant association between ASIC1 expression and malignant transformation of HCC, such as poor prognosis, metastasis and recurrence. Specifically, ASIC1 enhanced the migration and invasion capabilities of Li-7 cells in the in vivo experiment using an HCC lung metastasis mouse model, as well as in the in vitro experiments such as wound healing assay and Transwell assay. Furthermore, our comprehensive gene chip and molecular biology experiments revealed that ASIC1 promoted HCC migration and invasion by activating the PRKACA/AP-1 signaling pathway. Our findings indicate that targeting ASIC1 could have therapeutic potential for inhibiting HCC progression.
Assuntos
Canais Iônicos Sensíveis a Ácido , Carcinoma Hepatocelular , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Invasividade Neoplásica , Transdução de Sinais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Animais , Humanos , Camundongos , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/genética , Linhagem Celular Tumoral , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Masculino , Prognóstico , Proliferação de CélulasRESUMO
Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.
Assuntos
Antígenos CD , Antígenos de Protozoários , Macrófagos , Malária , Plasmodium yoelii , Animais , Feminino , Humanos , Camundongos , Antígenos CD/metabolismo , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/metabolismo , Antígenos de Superfície/imunologia , Antígenos de Superfície/metabolismo , Membrana Celular/metabolismo , Membrana Celular/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Malária/imunologia , Malária/parasitologia , NF-kappa B/metabolismo , NF-kappa B/imunologia , Plasmodium yoelii/imunologia , Ligação Proteica , Transdução de SinaisRESUMO
We conducted this systematic review and meta-analysis to clarify the trend of precocious puberty (PP) incidence after the COVID-19 outbreak and explore potential contributing factors, such as age at presentation and body mass index standard deviation score (BMI SDS). Children visiting pediatric endocrinology clinics for the first time for suspected PP were included. We searched databases until February 28, 2023 for studies reporting various indicators of PP incidence before and during the pandemic. Total numbers of events and observations were recorded. A meta-analysis was performed to compare the odds of PP, BMI SDS, and age at presentation between the two periods. The dose-response relationships between time points (by number of years away from the pandemic) and PP risk were explored. In summary, a total of 32 studies including 24,200 participants were recruited. COVID-19 pandemic was associated with the increasing odds of PP among children referred for suspicious condition (OR 1.96; 95% CI 1.56-2.47; I2 = 54%; P < 0.001). Sensitivity analysis confirmed the robustness of the findings. BMI SDS did not vary between the two periods, while age at presentation was lower following the pandemic. PP incidence increased more rapidly during the pandemic period than during the prepandemic period.
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Dihydropyrimidinase (DHPase) plays a crucial role in pyrimidine degradation, showcasing a broad substrate specificity that extends beyond pyrimidine catabolism, hinting at additional roles for this ancient enzyme. In this study, we solved the crystal structure of Pseudomonas aeruginosa DHPase (PaDHPase) complexed with the neurotransmitter γ-aminobutyric acid (GABA) at a resolution of 1.97 Å (PDB ID 8WQ9). Our structural analysis revealed two GABA binding sites in each monomer of PaDHPase. Interactions between PaDHPase and GABA molecules, involving residues within a contact distance of <4 Å, were examined. In silico analyses via PISA and PLIP software revealed hydrogen bonds formed between the side chain of Cys318 and GABA 1, as well as the main chains of Ser333, Ile335, and Asn337 with GABA 2. Comparative structural analysis between GABA-bound and unbound states unveiled significant conformational changes at the active site, particularly within dynamic loop I, supporting the conclusion that PaDHPase binds GABA through the loop-out mechanism. Building upon this molecular evidence, we discuss and propose a working model. The study expands the GABA interactome by identifying DHPase as a novel GABA-interacting protein and provides structural insight into the interaction between a dimetal center in the protein's active site and GABA. Further investigations are warranted to explore potential interactions of GABA with other DHPase-like proteins and to understand whether DHPase may have additional regulatory and physiological roles in the cell, extending beyond pyrimidine catabolism.
Assuntos
Amidoidrolases , Ácido gama-Aminobutírico , Amidoidrolases/química , Ácido gama-Aminobutírico/metabolismo , Proteínas , Neurotransmissores , PirimidinasRESUMO
The escalating incidence of metabolic pathologies such as obesity and diabetes mellitus underscores the imperative for innovative therapeutics targeting lipid metabolism modulation. Within this context, augmenting thermogenic processes in adipose cells emerges as a viable therapeutic approach. Given the limitations of previous ß3-adrenergic receptor (ß3-AR) agonist treatments in human diseases, there is an increasing focus on therapies targeting the ß2-adrenergic receptor (ß2-AR). Olodaterol (OLO) is a potent ß2-AR agonist that is a potential novel pharmacological candidate in this area. Our study explores the role and underlying mechanisms of OLO in enhancing brown adipose thermogenesis, providing robust evidence from in vitro and in vivo studies. OLO demonstrated a dose-dependent enhancement of lipolysis, notably increasing the expression of Uncoupling Protein 1 (UCP1) and raising the rate of oxygen consumption in primary brown adipocytes. This suggests a significant increase in thermogenic potential and energy expenditure. The administration of OLO to murine models noticeably enhanced cold-induced nonshivering thermogenesis. OLO elevated UCP1 expression in the brown adipose tissue of mice. Furthermore, it promoted brown adipocyte thermogenesis by activating the ß2-AR/cAMP/PKA signaling cascades according to RNA sequencing, western blotting, and molecular docking analysis. This investigation underscores the therapeutic potential of OLO for metabolic ailments and sheds light on the intricate molecular dynamics of adipocyte thermogenesis, laying the groundwork for future targeted therapeutic interventions in human metabolic disorders.
Assuntos
Adipócitos Marrons , Benzoxazinas , Termogênese , Camundongos , Humanos , Animais , Adipócitos Marrons/metabolismo , Simulação de Acoplamento Molecular , Termogênese/genética , Tecido Adiposo Marrom/metabolismo , Transdução de Sinais , Obesidade/metabolismo , Agonistas Adrenérgicos beta , Receptores Adrenérgicos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Non-alcoholic fatty liver disease (NAFLD) stands as the most prevalent hepatic disorder, with bariatric surgery emerging as the most effective intervention for NAFLD remission. Sleeve gastrectomy (SG) has notably ascended as the predominant procedure due to its comparative simplicity and consistent surgical outcomes. Nonetheless, the underlying mechanisms remain unclear. In this study, we probed the therapeutic potential of SG for NAFLD induced by a high-fat diet (HFD) in mice, with a focus on its impact on liver lipid accumulation, macrophage polarization, and the role of the histone methyltransferase Setdb2. SG prompted significant weight loss, diminished liver size and liver-to-body weight ratio, and enhanced liver function, evidenced by reduced serum levels of triglycerides (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination confirmed a reduction in liver lipid accumulation. Additionally, flow cytometry unveiled an increased proportion of M2 macrophages and a decrease in Setdb2 expression was shown in the SG group, suggesting an association between Setdb2 levels and postsurgical macrophage polarization. Furthermore, the conditional knockout of Setdb2 in mice further mitigated HFD-induced steatosis and promoted the M2 macrophage phenotype. Mechanistically, Setdb2 knockout in bone marrow-derived macrophages (BMDMs) favored M2 polarization, with RNA sequencing and western blotting analyses corroborating the upregulation of the PI3K/Akt signaling pathway. The effects of Setdb2 on macrophage activation were nullified by the PI3K inhibitor LY294002, suggesting that Setdb2 facilitates alternative macrophage activation through the PI3K/Akt signaling pathway. These comprehensive findings underscore the potential of SG as a therapeutic intervention for NAFLD by regulating the critical function of Setdb2 in macrophage polarization and activation, thereby offering novel insights into NAFLD pathogenesis and therapeutic targets.
Assuntos
Regulação para Baixo , Gastrectomia , Histona-Lisina N-Metiltransferase , Ativação de Macrófagos , Macrófagos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Masculino , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Fígado/patologia , Metabolismo dos LipídeosRESUMO
Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.
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Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Receptor de Morte Celular Programada 1/genética , Estudos Longitudinais , Antígenos do Núcleo do Vírus da Hepatite B , Linfócitos T CD8-PositivosRESUMO
Optical zoom is an essential function for many imaging systems including consumer electronics, biomedical microscopes, telescopes, and projectors. However, most optical zoom imaging systems have discrete zoom rates or narrow zoom ranges. In this work, a continuous optical zoom imaging system with a wide zoom range is proposed. It consists of a solid lens, two Alvarez lenses, and a camera with an objective. Each Alvarez lens is composed of two cubic phase plates, which have inverted freeform surfaces concerning each other. The movement of the cubic phase masks perpendicular to the optical axis is realized by the actuation of the dielectric elastomer. By applying actuation voltages to the dielectric elastomer, cubic phase masks are moved laterally and then the focal lengths of the two Alvarez lenses are changed. By adjusting the focal lengths of these two Alvarez lenses, the optical magnification is tuned. The proposed continuous optical zoom imaging system is built and the validity is verified by the experiments. The experimental results demonstrate that the zoom ratio is up to 10×, i.e., the magnification continuously changes from 1.58× to 15.80× when the lateral displacements of the cubic phase masks are about 1.0 mm. The rise and fall response times are 150â ms and 210â ms, respectively. The imaging resolution can reach 114 lp/mm during the optical zoom process. The proposed continuous optical imaging system is expected to be used in the fields of microscopy, biomedicine, virtual reality, etc.
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To enhance the performance of multi-junction photovoltaics, we investigated three different InP-based tunnel junction designs: p++-InGaAs/n++-InP tunnel junction, p++-InGaAs/i-InGaAs-/n++-InP tunnel junction, and p++-InGaAs/i-InGaAs/n++-InGaAs tunnel junction. The p++-InGaAs/i-InGaAs/n++-InGaAs tunnel junction demonstrated a peak tunneling current density of 495â A/cm2 and a resistivity of 9.3 × 10-4 Ωcm2, allowing the tunnel junction device to operate at a concentration over 30000 suns. This was achieved by inserting an undoped InGaAs quantum well at the p++-InGaAs/n++InGaAs junction interfaces, which enhanced its stability within the operating temperature range of multi-junction solar cells. Moreover, the p++-InGaAs/i-InGaAs/n++-InGaAs tunnel junction exhibited the lowest resistance.
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An erratum is presented to modify a calculating error in our published manuscript ["High-power 970â nm semiconductor disk laser" Opt. Express31, 43963 (2023)10.1364/OE.506462 [CrossRef]]. All results throughout the manuscript and its conclusions are unaffected by this correction and remain valid.
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Near-unity circular dichroism (CD) with high quality (Q)-factors has wide applications in chiral lasers, modulators, detectors, etc. In this work, we firstly suggest a feasible approach to realize near-unity CD (â¼0.94) with a high Q-factor (>2 × 104) supported by a toroidal dipole (TD) empowered superchiral quasi-bound states in the continuum (BICs) metasurface. Based on intensity, excellent electrical switching is achieved by adjusting the Fermi energy of the graphene on the metasurface. High refractive index sensitivity (136.2â nm/RIU) and figure of merit (1135â RIU-1) demonstrate its superior chiral sensing detection performance. Moreover, the near-unity CD displays a large robustness to the asymmetry offset. Our work paves a feasible avenue for well-designed superchiral quasi-BIC metasurfaces with high Q-factor near-unity CD for chiral applications in electrically tunable modulators, switches, sensors, etc.
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The layer-dependent Chern number (C) in MnBi_{2}Te_{4} is characterized by the presence of a Weyl semimetal state in the ferromagnetic coupling. However, the influence of a key factor, namely, the exchange coupling, remains unexplored. This study focuses on characterizing the C=2 state in MnBi_{2}Te_{4}, which is classified as a higher C state resulting from the anomalous n=0 Landau levels (LLs). Our findings demonstrate that the exchange coupling parameter strongly influences the formation of this Chern state, leading to a competition between the C=1 and 2 states. Moreover, the emergence of odd-even LL sequences, resulting from the breaking of LL degeneracy, provides compelling evidence for the strong exchange coupling strength. These findings highlight the significance of the exchange coupling in understanding the behavior of Chern states and LLs in magnetic quantum systems.