ABSTRACT
Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19+ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD PrkdcscidIl2rg-/- mice. Thus, decreasing CD19+ EVs holds high potential to improve the chemotherapeutic antitumor effect.
Subject(s)
B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Extracellular Vesicles/immunology , Animals , Antigens, CD19/immunology , Cell Line , Cell Line, Tumor , Female , HEK293 Cells , Herpesvirus 4, Human/immunology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , NIH 3T3 Cells , RNA, Messenger/immunology , Transcription, Genetic/immunology , rab27 GTP-Binding Proteins/immunologyABSTRACT
Schistosomiasis is caused by parasitic flatworms known as schistosomes and affects over 200 million people worldwide. Prevention of T cell exhaustion by blockade of PD-1 results in clinical benefits to cancer patients and clearance of viral infections, however it remains largely unknown whether loss of PD-1 could prevent or cure schistosomiasis in susceptible mice. In this study, we found that S. japonicum infection dramatically induced PD-1 expression in T cells of the liver where the parasites chronically inhabit and elicit deadly inflammation. Even in mice infected by non-egg-producing unisex parasites, we still observed potent induction of PD-1 in liver T cells of C57BL/6 mice following S. japonicum infection. To determine the function of PD-1 in schistosomiasis, we generated PD-1-deficient mice by CRISPR/Cas9 and found that loss of PD-1 markedly increased T cell count in the liver and spleen of infected mice. IL-4 secreting Th2 cells were significantly decreased in the infected PD-1-deficient mice whereas IFN-γ secreting CD4+ and CD8+ T cells were markedly increased. Surprisingly, such beneficial changes of T cell response did not result in eradication of parasites or in lowering the pathogen burden. In further experiments, we found that loss of PD-1 resulted in both beneficial T cell responses and amplification of regulatory T cells that prevented PD-1-deficient T cells from unleashing anti-parasite activity. Moreover, such PD-1-deficient Tregs exert excessive immunosuppression and express larger amounts of adenosine receptors CD39 and CD73 that are crucial for Treg-mediated immunosuppression. Our experimental results have elucidated the function of PD-1 in schistosomiasis and provide novel insights into prevention and treatment of schistosomiasis on the basis of modulating host adaptive immunity.
Subject(s)
Schistosoma japonicum , Schistosomiasis japonica , Animals , Humans , Immunosuppression Therapy , Mice , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor/genetics , T-Lymphocytes, RegulatoryABSTRACT
All-inorganic halide perovskite quantum dots (QDs) have recently received much attention due to their excellent optoelectronic properties. And their emission properties still need to be improved for further applications. Here, we demonstrated a remarkable emission enhancement of the CsPbBr3 QDs based on an Ag nanoparticle-Ag film plasmonic coupling structure. Through precise control of the gap distance between Ag nanoparticle and Ag film, the localized surface plasmon resonance (LSPR) peak was tuned to match the emission wavelength of the CsPbBr3 QDs. We achieved a 30-fold fluorescence intensity enhancement and a lower lasing threshold, which is 25% of that of the CsPbBr3 QDs without plasmonic coupling structure. It is attributed to that the plasmonic coupling structure exhibits an extremely strong local electric field owing to the coupling between LSPR of Ag nanoparticle and surface plasmon polariton of Ag film. This work provides an effective way to enhance the optical emission of perovskite QDs and promotes the further exploration of on-chip light source.
ABSTRACT
All-inorganic halide perovskite CsPbX3(X = Br/Cl/I)quantum dots have gained a considerable attention in the optoelectronic fields. However, the high cost and poor stability of the prepared CsPbX3 quantum dots (QDs) are inevitable challenges for their future practical applications. And the high-performance CsPbX3 QDs are always needed. Herein, a facile and low-cost synthesis scheme was adopted to prepare the CsPbBr3 QDs modified by lead bromide (PbBr2) and tetraoctylammonium bromide (TOAB) ligands at room temperature in open air. The prepared CsPbBr3 QDs exhibited a high photoluminescence quantum yield (PLQY) of 96.6% and a low amplified spontaneous emission (ASE) threshold of 12.6 µJ/cm2. Stable ASE intensity with little degradation was also realized from the CsPbBr3 QDs doped with PMMA. Furthermore, the enhanced ASE properties of the CsPbBr3 QDs-doped PMMA based on distributed feedback (DFB) substrate was achieved with a lower threshold of 3.6 µJ/cm2, which is 28.6% of that of the (PbBr2 + TOAB)-treated CsPbBr3 QDs without PMMA. This work exhibits a promising potential in the on-chip light source.
ABSTRACT
T and B cells continually recirculate between blood and secondary lymphoid organs. To promote their trans-endothelial migration (TEM), chemokine receptors control the activity of RHO family small GTPases in part via GTPase-activating proteins (GAPs). T and B cells express several RHO-GAPs, the function of most of which remains unknown. The ARHGAP45 GAP is predominantly expressed in hematopoietic cells. To define its in vivo function, we describe two mouse models where ARHGAP45 is ablated systemically or selectively in T cells. We combine their analysis with affinity purification coupled to mass spectrometry to determine the ARHGAP45 interactome in T cells and with time-lapse and reflection interference contrast microscopy to assess the role of ARGHAP45 in T-cell polarization and motility. We demonstrate that ARHGAP45 regulates naïve T-cell deformability and motility. Under physiological conditions, ARHGAP45 controls the entry of naïve T and B cells into lymph nodes whereas under competitive repopulation it further regulates hematopoietic progenitor cell engraftment in the bone marrow, and T-cell progenitor thymus seeding. Therefore, the ARGHAP45 GAP controls multiple key steps in the life of T and B cells.
Subject(s)
T-Lymphocytes , Virus Internalization , Animals , B-Lymphocytes , Cell Movement , GTPase-Activating Proteins/genetics , Lymph Nodes , Mice , Thymus GlandABSTRACT
The narrow band gap of silicene severely hinders its application in nanoelectronic devices. Therefore, it is significant to open the band gap of silicene and maintain its high carrier mobility. And for that, the adsorption of different coverage superhalogens BO2 on the silicene surface have been investigated based on density functional theory and the CALYPSO method. The results show that BO2 unit prefers to adsorb on silicene with adjacent mode irrespective of the size of substrate. The electronic structure analysis indicates that the density of states near the Fermi level are mainly contributed by Si-p and BO2-p orbitals. (BO2)n-silicene exhibits metallic character with the exception of (BO2)2 adsorbed on 4 × 4 supercell. As for (BO2)2-silicene, silicene transforms from a gapless direct semiconductor to an indirect semiconductor. Furthermore, the effective electron mass of two BO2 superhalogens on 4 × 4 silicene is estimated and found to be smaller than that of graphene. It is expected to result in higher electron mobility.
ABSTRACT
The immune balance of the respiratory tract is strictly regulated. Extracellular vesicles (EVs) have been reported to participate in maintaining the immune balance in the intestinal tract, but whether they are involved in regulation of the immune balance in the respiratory tract has yet to be revealed. In this study, we found that physiological EVs from lungs of WT mice (L-EVs) could be isolated, which contained the immunosuppressive cytokines TGF-ß1 and IL-10. Among L-EV subsets, only the CD8α+CD11c+ EV subset was positive for TGF-ß1 and IL-10 and could inhibit CD4+ T cell proliferation via TGF-ß1 in vitro and relieve murine asthmatic symptoms. Mechanistically, L-EVs were effective at inhibiting OVA peptide-specific CD4+ T cell proliferation in a TGF-ß1- and IL-10-dependent manner. In addition, they could prevent CD4+ T cells from hilar lymph nodes from secreting IL-4, IL-9, and IL-17A via IL-10 ex vivo, suggesting inhibition of Th2, Th9, and Th17 cell responses. Altogether, our results indicate that EVs from the lungs are involved in control of the immune balance in the respiratory tract, which reveals a novel mechanism in the maintenance of respiratory tract immune homeostasis.
Subject(s)
CD11c Antigen/immunology , CD8 Antigens/immunology , Extracellular Vesicles/immunology , Homeostasis/immunology , Interleukin-10/immunology , Lung/immunology , Transforming Growth Factor beta1/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Cell Proliferation/physiology , Female , Interleukin-17/immunology , Lymph Nodes/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BLABSTRACT
To explore stable polynuclear magnetic superhalogens, we perform an unbiased structure search for polynuclear iron-based systems based on pseudohalogen ligand CN using the CALYPSO method in conjunction with density functional theory. The superhalogen properties, magnetic properties, and thermodynamic stabilities of neutral and anionic Fe2(CN)5 and Fe3(CN)7 clusters are investigated. The results show that both of the clusters have superhalogen properties due to their electron affinities (EAs) and that vertical detachment energies (VDEs) are significantly larger than those of the chlorine element and their ligand CN. The distribution of the extra electron analysis indicates that the extra electron is aggregated mainly into pseudohalogen ligand CN units in Fe2(CN)5¯ and Fe3(CN)7¯ cluster. These features contribute significantly to their high EA and VDE. Besides superhalogen properties, these two anionic clusters carry a large magnetic moment just like the Fe2F5¯ cluster. Additionally, the thermodynamic stabilities are also discussed by calculating the energy required to fragment the cluster into various smaller stable clusters. It is found that Fe(CN)2 is the most favorable fragmentation product for anionic Fe2(CN)5¯ and Fe3(CN)7¯ clusters, and both of the anions are less stable against ejection of Fe atoms than Fe(CN)n-x.
ABSTRACT
On the basis of the first-principles techniques, we perform the structure prediction for MoB2. Accordingly, a new ground-state crystal structure WB2 (P63/mmc, 2 fu/cell) is uncovered. The experimental synthesized rhombohedral R3Ì m and hexagonal AlB2, as well as theoretical predicted RuB2 structures, are no longer the most favorite structures. By analyzing the elastic constants, formation enthalpies, and phonon dispersion, we find that the WB2 phase is thermodynamically and mechanically stable. The high bulk modulus B, shear modulus G, low Poisson's ratio ν, and small B/G ratio are benefit to its low compressibility. When the pressure is 10 GPa, a phase transition is observed between the WB2-MoB2 and the rhombohedral R3Ì m MoB2 phases. By analyzing the density of states and electron density, we find that the strong covalent is formed in MoB2 compounds, which contributes a great deal to its low compressibility. Furthermore, the low compressibility is also correlated with the local buckled structure.
ABSTRACT
The structure and bonding nature of neutral and negatively charged BxAlyH2 (x + y = 7, 8, 9) clusters are investigated with the aid of previously published experimental photoelectron spectra combined with the present density functional theory calculations. The comparison between the experimental photoelectron spectra and theoretical simulated spectra helps to identify the ground state structures. The accuracy of the obtained ground state structures is further verified by calculating their adiabatic electron affinities and vertical detachment energies and comparing them against available experimental data. The results show that the structures of BxAlyH2 transform from three-dimensional to planar structures as the number of boron atoms increases. Moreover, boron atoms tend to bind together forming Bn units. The hydrogen atoms prefer to bind with boron atoms rather than aluminum atoms. The analyses of the molecular orbital on the ground state structures further support the abovementioned results.
ABSTRACT
PURPOSE: Tumour-cell-derived exosomes (Exo) have been proposed as a new kind of drug carrier, and heat stress can promote release of exosomes from tumour cells. This study investigated the impact of heat stress on the quantity of doxorubicin in exosomes from the same number of doxorubicin-treated MFC-7 tumour cells and their anti-tumour effects. MATERIALS AND METHODS: Exosomes were isolated from phosphate-buffered saline (Exo), doxorubicin (Exo-Dox) or doxorubicin combined with heat-stress-treated (Exo-Dox-HS) MCF-7 cells. The content of doxorubicin in the exosomes was determined by flow cytometry. The effects of individual types of exosomes on the MCF-7 cell proliferation and apoptosis as well as the tumour growth were determined by MTT assay, flow cytometry and murine xenograft tumour modelling. RESULTS: We found that the amount of Exo-Dox-HS was higher than that of Exo-Dox from the same number of MCF-7 cells, and Exo-Dox-HS contained higher levels of doxorubicin than Exo-Dox from the same number of cells. Exo-Dox and Exo-Dox-HS, but not Exo or 10 µg/mL doxorubicin, significantly inhibited the MCF-7 cell proliferation and triggered MCF-7 cell apoptosis, associated with increased levels of cleaved caspase-3 and -8 and morphological changes in MCF-7 cells. Treatment with Exo-Dox and Exo-Dox-HS inhibited the growth of implanted breast tumours in mice. CONCLUSIONS: Our study indicated that heat stress increased the quantity of doxorubicin-containing exosomes from tumour cells, and enhanced the anti-tumour effect of exosomes from the doxorubicin-treated tumour cells. Our findings may aid in designing new strategies for cancer therapy by combination of chemotherapy and hyperthermia.
Subject(s)
Doxorubicin/therapeutic use , Neoplasms/genetics , Animals , Apoptosis , Exosomes , Heat-Shock Response , Humans , MiceABSTRACT
We have investigated the performances of organic light-emitting diodes (OLED) with different spacer, the structure was fabricated as ITO/MoO3 (40 nm)/NPB(40 nm)/TCTA(10 nm)/CBP:GIr114:R-4B2%(30 nm)/spacer (3 nm)/CBP: GIr114%:R-4B2%(30 nm)/BCP(10 nm)/Alq3 (40 nm)/LiF(1 nm)/Al(100 nm), the spacers were CBP, TCTA, TPBI and BCP separately, GIr1 and R-4B were green and red phosphorescent dye respectively. The results showed that compared to the reference device utilized CBP as the spacer layer, TCTA, TPBI and BCP had higher current efficiency in excess of 59%, 79% and 93%, the maximum current efficiency of 16.91 cd x A(-1) was achieved with BCP as the spacer at voltage of 5 V, TPBI and BCP as the spacer layer obtained the higher current density and lower efficiency roll-off. We attributed to these results to the follow reasons, the first was that carriers and excitons were limited to a narrow recombination region because of TCTA with higher LUMO energy level and triplet energy, which improved the probability of carriers recombination, in addition, more serious quenching at higher current density. The second reason was that TPBI and BCP had the higher HOMO energy level and electron mobility, which broadened excitons recombination zone. In addition, the spacer layer caused the accumulation of electrons or holes and the formation of high space electric field, leading to carrier injection and transport more effectively. In particular, we obtained a better stability of phosphorescent organic light-emitting diodes since the way for the red and green co-doped with host material.
ABSTRACT
Magnetic-plasmonic nanoparticles (NPs) have attracted great interest in many fields because they can exhibit more physical and chemical properties than individual magnetic or plasmonic NPs. In this work, we synthesized Au- or Ag-decorated Fe3O4 nanoparticles coated with PEI (Fe3O4-PEI-M (M = Au or Ag) NPs) using a simple method. The influences of the plasmonic metal NPs' (Au or Ag) coating density on the magnetic and plasmonic properties of the Fe3O4-PEI-M (M = Au or Ag) NPs were investigated, and the density of the plasmonic metal NPs coated on the Fe3O4 NPs surfaces could be adjusted by controlling the polyethyleneimine (PEI) concentration. It showed that the Fe3O4-PEI-M (M = Au or Ag) NPs exhibited both magnetic and plasmonic properties. When the PEI concentration increased from 5 to 35 mg/mL, the coating density of the Au or Ag NPs on the Fe3O4 NPs surfaces increased, the corresponding magnetic intensity became weaker, and the plasmonic intensity was stronger. At the same time, the plasmonic resonance peak of the Fe3O4-PEI-M (M = Au or Ag) NPs was red shifted. Therefore, there was an optimal coverage of the plasmonic metal NPs on the Fe3O4 NPs surfaces to balance the magnetic and plasmonic properties when the PEI concentration was between 15 and 25 mg/mL. This result can guide the application of the Fe3O4-M (M = Au or Ag) NPs in the biomedical field.
ABSTRACT
Visual anomaly detection is an essential component in modern industrial manufacturing. Existing studies using notions of pairwise similarity distance between a test feature and nominal features have achieved great breakthroughs. However, the absolute similarity distance lacks certain generalizations, making it challenging to extend the comparison beyond the available samples. This limitation could potentially hamper anomaly detection performance in scenarios with limited samples. This article presents a novel sparse feature representation anomaly detection (SFRAD) framework, which formulates the anomaly detection as a sparse feature representation problem; and notably proposes an anomaly score by orthogonal matching pursuit (ASOMP) as a novel detection metric. Specifically, SFRAD calculates the Gaussian kernel distance between the test feature and its sparse representation in the nominal feature space for anomaly detection. Here, the orthogonal matching pursuit (OMP) algorithm is adopted to achieve the sparse feature representation. Moreover, to construct a low-redundancy memory bank storing the basis features for sparse representation, a novel basis feature sampling (BFS) algorithm is proposed by considering both the maximum coverage and the optimum feature representation simultaneously. As a result, SFRAD incorporates both the advantages of absolute similarity and linear representation; and this enhances the generalization in low-shot scenarios. Extensive experiments on the MVTec anomaly detection (MVTec AD), Kolektor surface-defect dataset (KolektorSDD), Kolektor surface-defect dataset 2 (KolektorSDD2), MVTec logical constraints anomaly detection (MVTec LOCO AD), Visual anomaly (VISA), Modified national institute of standards and technology (MNIST), and CIFAR-10 datasets demonstrate that our proposed SFRAD outperforms the previous methods and achieves state-of-the-art unsupervised anomaly detection performance. Notably, significantly improved outcomes and results have also been achieved on low-shot anomaly detection. Code is available at https://github.com/fanghuisky/SFRAD.
ABSTRACT
Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2â¢-), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2â¢- changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2â¢- and HSCs targeting peptides. We observe that O2â¢- in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2â¢-, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.
Subject(s)
Hepatic Stellate Cells , Superoxides , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/immunology , Animals , Superoxides/metabolism , Mice , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Humans , Optical Imaging/methods , Immune Evasion , CD8-Positive T-Lymphocytes/immunology , Mice, Inbred C57BL , Tumor Escape , MaleABSTRACT
The present paper uses the R-4B as phosphor dopant, the main body was CBP, regulation carrier composite layer was BCP, and the device structure was ITO/MoO3 (30)/NPB (40)/TCTA (10)/CBP : R-4B(6%)(15)/BCP(chi)/CBP : R-4B(6%) (15)/BCP(10)/Alq3 (40)/LiF/Al. In the device, chi was the thickness of the BCP with five different thickness of the device. At the same time, another contrast device was made, which had been optimized at MoO3 without regulated BCP layer. The result shows that the luminous area was 1.18 cm2, BCP was 4, MoO3 was 30 nm, its performance was the best, light voltage was 4 V, maximum efficiency was 18. 9 cd x A(-1), its corresponding EL main peak was at 612 nm, and color coordinates was (0.643, 0.353), getting stable and high efficient red phosphor OLED devices.
ABSTRACT
The high-power white LED was prepared based on the high thermal conductivity aluminum, blue chips and YAG phosphor. By studying the spectral of different junction temperature, we found that the radiation spectrum of white LED has a minimum at 485 nm. The radiation intensity at this wavelength and the junction temperature show a good linear relationship. The LED junction temperature was measured based on the formula of relative spectral intensity and junction temperature. The result measured by radiation intensity method was compared with the forward voltage method and spectral method. The experiment results reveal that the junction temperature measured by this method was no more than 2 degrees C compared with the forward voltage method. It maintains the accuracy of the forward voltage method and overcomes the small spectral shift of spectral method, which brings the shortcoming on the results. It also had the advantages of practical, efficient and intuitive, noncontact measurement, and non-destruction to the lamp structure.
ABSTRACT
Utilizing GIr1(green) and R-4B(red) phosphorescent dye, organic light-emitting diodes with different doping orders on red and green light-emitting layers were fabricated. The authors investigated the luminescent properties of devices combined with the effect of electron (TCTA) and hole (BCP) blocking layer. The results showed that the great impacts on spectrum, light efficiency, luminance and luminescent color were produced based on different doping order, and the authros also found the strong emission peak at the interface of the BCP and CBP layer. With the use of the red and green doping type, 0.527 mA x cm(-2), 104 cd x m(-2), 19.75 cd x A(-1) and (0.371 7, 0.576 8) could be reached, respectively. The reasons were that on the one hand, because of large difference between energy levels of host material CBP and doping material GIr1, R-4B, and charge trapping and hopping via dopants were the main mechanism of change; on the other hand, for the different energy levels between dopants and blocking layers, the doping sequence could affect barrier distribution, and then affect the electric field distribution.
ABSTRACT
The present paper mainly studies the influence of the junction temperature on the white LED spectral characteristics of the mixture of the DCJTB and YAG: Ce3+ phosphor. With layered coating of YAG phosphor and organic materials DCJTB on the LED chip with the method of hierarchical point powder, the color rendering index of the device will reach up to 90. The junction temperature can be measured conveniently and accurately with the integrated LED cooling pad which was developed by the laboratory. Experiments show that: the rise of the junction temperature can make the radiation amplitude of the blue chip decline continuously. The yellow radiation amplitude of YAG phosphor which is excited by radiation first increases and then decreases, the red spectrum is blue-shifted, the color rendering index of the device decreased linearly, while the color temperature first increases and then decreases.
ABSTRACT
SnO2 has attracted much attention due to its low-temperature synthesis (ca. 140 °C), high electron mobility, and low-cost manufacturing. However, lattice mismatch and oxygen vacancies at the SnO2/CsPbI3-xBrx interface generally lead to undesirable nonradiative recombination in optoelectronic devices. The traditional TiO2 used as the electron transport layer (ETL) for all-inorganic perovskite solar cells (PSCs) requires high-temperature sintering and crystallization, which are not suitable for the promising flexible PSCs and tandem solar cells, raising concerns about surface defects and device uniformity. To address these challenges, we present a bilayer ETL consisting of a SnO2 layer using electron beam evaporation and a TiO2 layer through the hydrothermal method, resulting in an enhanced performance of the perovskite solar cell. The bilayer device exhibits an improved power conversion efficiency of 11.48% compared to the single-layer device (8.09%). The average fill factor of the bilayer electron transport layer is approximately 15% higher compared to the single-layer electron transport layer. Through a systematic investigation of the use of ETL for CsPb3-xBrx PSCs on optical and electronic properties, we demonstrate that the SnO2/TiO2 is an efficient bilayer ETL for PSCs as it significantly enhances the charge extraction capability, suppresses carrier recombination at the ETL/perovskite interface, facilitates efficient photogenerated carrier separation and transport, and provides high current density and reduced hysteresis.