RESUMEN
Impedance matching modulation of the electromagnetic wave (EMW) absorbers toward broad effective absorption bandwidth (EAB) is the ultimate aim in EMW attenuation applications. Here, a Joule heating strategy is reported for preparation of the Co-loaded carbon (Co/C) absorber with tunable impedance characteristics. Typically, the size of the Co can be regulated to range from single-atoms to clusters, and to nanocrystals. The varied sizes of the Co combined with different graphitization degrees of carbon can result in different relative input impedances and electromagnetic loss, leading to the tunable EMW absorption properties of the Co/C absorber. By meticulously coalescing the different prepared Co/C, the working frequency can be easily tuned, covering Ku, X, and C bands. Furthermore, the Co/C demonstrates a high EMW attenuation due to its unique dielectric loss capability and magnetic loss characteristics. The abundant interfaces of Co/C can also contribute to the enhanced interfacial polarization for improving EMW attenuation. This work demonstrates the importance of optimizing the metal and carbon interaction to the impedance matching toward wide EAB of the EMW absorbers.
RESUMEN
Alternative 3-dimensional (3D) skin models that replicate in vivo human skin are required to investigate important events during wound healing, such as collective cell migration, epidermal layer formation, dermal substrate formation, re-epithelialisation and collagen production. In this study, a matched human 3D skin equivalent model (3D-SEM) was developed from human skin cells (fibroblast and keratinocytes), characterised using haematoxylin and eosin, immunofluorescence staining and microRNA profiling. The 3D-SEM was then functionally tested for its use in wound healing studies. Mesenchymal stem cells (MSCs) were isolated and characterised according to the criteria stipulated by the International Society for Cell Therapy. Cytokine and growth factor secretions were analysed by enzyme-linked immunosorbent assay. MSC-conditioned medium (MSC-CM) was then tested for wound healing capacity using the developed 3D-SEM at different timepoints i.e., at one, two and four weeks. The constructed 3D-SEM showed consistent development of skin-like structures composed of dermal layers and epidermal layers, with the ability to express epidermal differentiation markers and full stratification. They also showed prolonged longevity in culture media, retaining full differentiation and stratification within the four weeks. MicroRNA profiling revealed a strong correlation in microRNA expression between the developed 3D-SEM and the original native skin (p<0.001; R=0.64). Additionally, MSC-CM significantly enhanced migration, proliferation and differentiation of epidermal cells in the wounded models compared to control models at the different timepoints. In conclusion, in this study, the developed 3D-SEM mimicked native skin at the cellular and molecular levels, and clearly showed the important stages of skin regeneration during the healing process. MSC secretome contains growth factors that play a pivotal role in the healing process and could be used as a therapeutic option to accelerate skin healing.
Asunto(s)
Células Madre Mesenquimatosas , Cicatrización de Heridas , Humanos , Medios de Cultivo Condicionados/farmacología , Cicatrización de Heridas/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Piel/lesiones , Piel/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células CultivadasRESUMEN
Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1⺠CLEC9A⺠DCs and CD1c⺠DCs are murine CD103⺠DCs and CD64⻠CD11b⺠DCs. In addition, human tissues also contain CD14⺠cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14⺠cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14⺠monocytes and dermal CD14⺠cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14⺠cells are CD11b⺠CD64⺠monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.
Asunto(s)
Receptores de Lipopolisacáridos/metabolismo , Macrófagos/inmunología , Piel/inmunología , Animales , Antígeno CD11b/biosíntesis , Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Movimiento Celular/inmunología , Células Cultivadas , Células Dendríticas/inmunología , Femenino , Humanos , Memoria Inmunológica/inmunología , Ratones , Ratones Transgénicos , Receptores de IgG/biosíntesis , Piel/citología , Linfocitos T/inmunologíaRESUMEN
During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.
Asunto(s)
Arginasa/metabolismo , Células Dendríticas/enzimología , Células Dendríticas/inmunología , Feto/inmunología , Tolerancia Inmunológica , Linfocitos T/inmunología , Adulto , Movimiento Celular , Proliferación Celular , Citocinas/biosíntesis , Citocinas/inmunología , Feto/citología , Feto/enzimología , Humanos , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Linfocitos T/citología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Receptores Toll-Like/inmunologíaRESUMEN
Developing high-performance absorbers with a broad absorption band is a considerable challenge. Herein, carbon nanotube-modified Cu0.48Ni0.16Co2.36O4/CuO (C-CuNiCoO) composites were prepared using the one-pot hydrothermal method. The composites show good light scattering ability and longer light path due to their urchin-like structures, and lead to perfect absorption above 90% in optical ranges. Moreover, in the infrared ranges, the composites exhibited a high average mass extinction coefficient of 2.52 m2.g-1. The unique carbon modification favored the balance between impedance and strong loss capacity. Consequently, C-CuNiCoO achieved excellent absorption performance with a reflection loss up to -40.5 dB at 17.1 GHz. This study opens a new pathway for designing and synthesizing wideband absorption materials.
RESUMEN
Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8(+) T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141(hi) DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c(+) and CD14(+) tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141(hi) DCs were closely related to blood CD141(+) DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting.
Asunto(s)
Antígenos CD/metabolismo , Reactividad Cruzada/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Cadenas alfa de Integrinas/metabolismo , Animales , Antígenos/inmunología , Movimiento Celular/inmunología , Quimiocina CXCL10/biosíntesis , Perfilación de la Expresión Génica , Humanos , Inmunofenotipificación , Células de Langerhans/inmunología , Células de Langerhans/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Ratones , Piel/inmunología , Transcriptoma , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Production of multicarbon (C2+ ) liquid fuels is a challenging task for electrocatalytic CO2 reduction, mainly limited by the stabilization of reaction intermediates and their subsequent C-C couplings. In this work, we report a unique catalyst, the coordinatively unsaturated Cu sites on amorphous CuTi alloy (a-CuTi@Cu) toward electrocatalytic CO2 reduction to multicarbon (C2-4 ) liquid fuels. Remarkably, the electrocatalyst yields ethanol, acetone, and n-butanol as major products with a total C2-4 faradaic efficiency of about 49 % at -0.8â V vs. reversible hydrogen electrode (RHE), which can be maintained for at least 3â months. Theoretical simulations and in situ characterization reveals that subsurface Ti atoms can increase the electron density of surface Cu sites and enhance the adsorption of *CO intermediate, which in turn reduces the energy barriers required for *CO dimerization and trimerization.
RESUMEN
Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and stimulatory function. Current knowledge on the functional impact of semimature DC is limited to CD4+ T cell proliferation and cytokine production. Little is known about the molecular basis underpinning the functional effects of Treg-treated DC (Treg-DC). We present novel evidence that Treg-DC skewed CD4+ naive T cell polarization toward a regulatory phenotype and impaired CD8+ T cell allo-reactive responses, including their ability to induce target tissue damage in a unique in vitro human graft-versus-host disease skin explant model. Microarray analysis clustered Treg-DC as a discrete population from mature-DC and immature-DC, with 51 and 93 genes that were significantly over- or underexpressed, respectively, compared with mature-DC. Quantitative real-time PCR analysis revealed an intermediate expression level of CD38, CD83, CD80 and CD86 mRNA in Treg-DC, lower than mature-DC, higher than immature-DC. We also observed an attenuation of NF-κB pathway, an upstream regulator of the aforementioned genes, concomitant with reduced expression of two NF-κB-signaling related genes RELB and NFκBIZ, in the Treg-DC, together with an increased expression of Wnt5a, a negative regulator of DC differentiation. We further confirmed that the Treg-DC-mediated skewed CD4+ naive T cell polarization resulted from decreased IL-12 secretion by Treg-DC, which may be post-transcriptionally modulated by decreased expression of microRNA-155 in Treg-DC. To our knowledge, this is the first study demonstrating a transcriptional modulation of DC function by human Treg, partially via attenuation of the NF-κB signaling pathway and upregulation of Wnt5a, suggesting Treg may interfere with DC reprogramming during maturation, thereby modulating DC function.
Asunto(s)
Diferenciación Celular/inmunología , Células Dendríticas/inmunología , Linfocitos T Reguladores/inmunología , Células Cultivadas , Técnicas de Cocultivo , Células Dendríticas/citología , Citometría de Flujo , Regulación de la Expresión Génica/inmunología , Humanos , Activación de Linfocitos/inmunología , FN-kappa B/inmunología , FN-kappa B/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/inmunología , Transcripción Genética , Proteína Wnt-5a/inmunología , Proteína Wnt-5a/metabolismoRESUMEN
Utilization of visible and near-infrared light has always been the pursuit of photocatalysis research. In this article, an approach is developed to integrate dual plasmonic nanostructures with TiO2 semiconductor nanosheets for photocatalytic hydrogen production in visible and near-infrared spectral regions. Specifically, the Au nanocubes and nanocages used in this work can harvest visible and near-infrared light, respectively, and generate and inject hot electrons into TiO2 . Meanwhile, Pd nanocubes that can trap the energetic electrons from TiO2 and efficiently participate in the hydrogen evolution reaction are employed as co-catalysts for improved catalytic activity. Enabled by this unique integration design, the hydrogen production rate achieved is dramatically higher than those of its counterpart structures. This work represents a step toward the rational design of semiconductor-metal hybrid structures for broad-spectrum photocatalysis.
RESUMEN
Extracellular vesicles (EV) are rich in small RNA; however, a frequent caveat can be low abundance of EV RNA content, especially in clinical studies. NanoString MicroRNA Assays allow for multiplexed profiling of n = 800 mature microRNAs and can be applied to assess EV microRNA cargo. Here, we describe a method to adapt NanoString nCounter microRNA profiling to assess mature microRNA expression in low-concentration RNA samples, including concentrating the RNA, quantifying the RNA, and performing the NanoString protocol. Twelve samples can be assessed at one time using this method.
Asunto(s)
Vesículas Extracelulares , MicroARNs , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroARNs/genética , MicroARNs/análisis , Humanos , Perfilación de la Expresión Génica/métodosRESUMEN
Using the trapped rainbow effect to slow down or even stop light has been widely studied. However, high loss and energy leakage severely limited the development of rainbow devices. Here, we observed the negative Goos-Hänchen effect in film samples across the entire visible spectrum. We also discovered an amber rainbow ribbon and an optical black hole due to perfect back reflection in optical waveguides, where little light leaks out. Not only does the amber rainbow ribbon effect show an automatic frequency selection response, as predicted by single frequency theoretical models and confirmed by experiments, it also shows spatial periodic regulation, resulting from broadband omnidirectional visible metamaterials prepared by disordered assembly systems. This broadband light trapping system could play a crucial role in the fields of optical storage and information processing when being used to construct ultra-compact modulators and other tunable devices.
RESUMEN
Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1ß on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics.
RESUMEN
The human syndrome of dendritic cell, monocyte, B and natural killer lymphoid deficiency presents as a sporadic or autosomal dominant trait causing susceptibility to mycobacterial and other infections, predisposition to myelodysplasia and leukemia, and, in some cases, pulmonary alveolar proteinosis. Seeking a genetic cause, we sequenced the exomes of 4 unrelated persons, 3 with sporadic disease, looking for novel, heterozygous, and probably deleterious variants. A number of genes harbored novel variants in person, but only one gene, GATA2, was mutated in all 4 persons. Each person harbored a different mutation, but all were predicted to be highly deleterious and to cause loss or mutation of the C-terminal zinc finger domain. Because GATA2 is the only common mutated gene in 4 unrelated persons, it is highly probable to be the cause of dendritic cell, monocyte, B, and natural killer lymphoid deficiency. This disorder therefore constitutes a new genetic form of heritable immunodeficiency and leukemic transformation.
Asunto(s)
Linfocitos B/patología , Células Dendríticas/patología , Susceptibilidad a Enfermedades/etiología , Exones/genética , Factor de Transcripción GATA2/genética , Células Asesinas Naturales/patología , Tejido Linfoide/patología , Monocitos/patología , Mutación/genética , Factor de Transcripción GATA2/química , Humanos , Conformación ProteicaRESUMEN
Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Epigénesis Genética , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patologíaRESUMEN
Osteoarthritis (OA) is a joint degenerative pathology characterized by mechanical and inflammatory damages affecting synovium, articular cartilage (AC), and subchondral bone (SB). Several in vitro, in vivo, and ex vivo models are developed to study OA, but to date the identification of specific pharmacological targets seems to be hindered by the lack of models with predictive capabilities. This study reports the development of a biomimetic in vitro model of AC and SB interface. Gellan gum methacrylated and chondroitin sulfate/dopamine hydrogels are used for the AC portion, whereas polylactic acid functionalized with gelatin and nanohydroxyapatite for the SB. The physiological behavior of immortalized stem cells (Y201s) and Y201s differentiated in chondrocytes (Y201-Cs), respectively, for the SB and AC, is demonstrated over 21 days of culture in vitro in healthy and pathological conditions, whilst modeling the onset of cytokines-induced OA. The key metrics are: lower glycosaminoglycans production and increased calcification given by a higher Collagen X content, in the AC deep layer; higher expression of pro-angiogenic factor (vegf) and decreased expression of osteogenic markers (coll1, spp1, runx2) in the SB. This novel approach provides a new tool for studying the development and progression of OA.
Asunto(s)
Cartílago Articular , Osteoartritis , Humanos , Huesos/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrocitos , Osteoartritis/metabolismo , Osteoartritis/patología , Osteogénesis , Ingeniería de Tejidos/métodosRESUMEN
Extracellular vesicles (EV) and the microRNAs that they contain are increasingly recognised as a rich source of informative biomarkers, reflecting pathological processes and fundamental biological pathways and responses. Their presence in biofluids makes them particularly attractive for biomarker identification. However, a frequent caveat in relation to clinical studies is low abundance of EV RNA content. In this study, we used NanoString nCounter technology to assess the microRNA profiles of n = 64 EV low concentration RNA samples (180-49125 pg), isolated from serum and cell culture media using precipitation reagent or sequential ultracentrifugation. Data was subjected to robust quality control parameters based on three levels of limit of detection stringency, and differential microRNA expression analysis was performed between biological subgroups. We report that RNA concentrations > 100 times lower than the current NanoString recommendations can be successfully profiled using nCounter microRNA assays, demonstrating acceptable output ranges for imaging parameters, binding density, positive/negative controls, ligation controls and normalisation quality control. Furthermore, despite low levels of input RNA, high-level differential expression analysis between biological subgroups identified microRNAs of biological relevance. Our results demonstrate that NanoString nCounter technology offers a sensitive approach for the detection and profiling of low abundance EV-derived microRNA, and may provide a solution for research studies that focus on limited sample material.
RESUMEN
Light utilization largely governs the performance of CO2 photoconversion, whereas most of the materials that are implemented in such an application are restricted in a narrow spectral absorption range. Plasmonic metamaterials with a designable regular pattern and facile tunability are excellent candidates for maximizing light absorption to generate substantial hot electrons and thermal energy. Herein, a concept of coupling a Au-based stacked plasmonic metamaterial with single Cu atoms in alloy, as light absorber and catalytic sites, respectively, is reported for gas-phase light-driven catalytic CO2 hydrogenation. The metamaterial structure works in a broad spectral range (370-1040 nm) to generate high surface temperature for photothermal catalysis, and also induces strong localized electric field in favor of transfer of hot electrons and reduced energy barrier in CO2 hydrogenation. This work unravels the significant role of a strong localized electric field in photothermal catalysis and demonstrates a scalable fabrication approach to light-driven catalysts based on plasmonic metamaterials.
RESUMEN
[This corrects the article DOI: 10.3389/fimmu.2022.903796.].
RESUMEN
Cholangiocarcinoma (CCA) is a type of cancer with a relatively low morbidity, but poor prognosis. Aberrant long non-coding RNA (lncRNA) expression has been observed in the pathological development of CCA. In the present study, lncRNA long intergenic non-protein coding RNA 630 (LINC00630) was found to be significantly upregulated in CCA tissues and cultured cells. LINC00630 expression was positively associated with histological differentiation, TNM stage and lymph node invasion. Short hairpin RNA (sh)-LINC00630 transfection could effectively decrease CCA cell proliferation, migration and invasion. Further investigations found that LINC00630 could interact with microRNA (miR)-199a, which specifically targeted fibroblast growth factor 7 (FGF7) for degradation. FGF7 overexpression restored the sh-LINC00630 transfection-induced decrease in CCA cell proliferation, migration and invasion. In conclusion, LINC00630 significantly promoted CCA cell proliferation, migration and invasion by upregulating FGF7 through miR-199a sponging.