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1.
Cancer Immunol Immunother ; 73(5): 81, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554184

RESUMO

Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.


Assuntos
Células Matadoras Naturais , Neoplasias , Humanos , Ligantes , Imunoterapia , Linfócitos do Interstício Tumoral , Neoplasias/metabolismo
2.
Small ; 20(31): e2312006, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38431945

RESUMO

A high soluble and stable ɛ-Zn(OH)2 precursor is synthesized at below room temperature to efficiently prepare ZnO whiskers. The experimental results indicate that the formation of ZnO whiskers is carried out mainly via two steps: the formation of ZnO seeds from ɛ-Zn(OH)2 via the in situ solid conversion, and the following growth of whiskers via dissolution-precipitation route. The decrease of temperature from 25 to 5 °C promotes the formation of ɛ-Zn(OH)2 with higher solubility and stability, which balances the conversion and dissolution rates of precursor. The Rietveld refinement, DFT calculations and MD simulations reveal that the primary reason for these characteristics is the expansion of ɛ-Zn(OH)2 lattice due to temperature, causing difficulties in the dehydration of adjacent ─OH. Simultaneously, the larger specific surface area favors the dissolution of ɛ-Zn(OH)2. Based on this precursor, well-dispersed ZnO whiskers with 9.82 µm in length, 242.38 nm in diameter, and an average aspect ratio of 41 are successfully synthesized through a SDSN-assisted hydrothermal process at 80 °C. The process has an extremely high solid content of 2.5% (mass ratio of ZnO to solution) and an overall yield of 92%, which offers a new approach for the scaled synthesis of high aspect ratio ZnO whiskers by liquid-phase method.

3.
Int J Mol Sci ; 25(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39063077

RESUMO

Rice straw is an agricultural waste, the disposal of which through open burning is an emerging challenge for ecology. Green manufacturing using straw returning provides a more avant-garde technique that is not only an effective management measure to improve soil fertility in agricultural ecosystems but also nurtures environmental stewardship by reducing waste and the carbon footprint. However, fresh straw that is returned to the field cannot be quickly decomposed, and screening microorganisms with the capacity to degrade straw and understanding their mechanism of action is an efficient approach to solve such problems. This study aimed to reveal the potential mechanism of influence exerted by exogenous degradative bacteria (ZJW-6) on the degradation of straw, growth of plants, and soil bacterial community during the process of returning rice straw to the soil. The inoculation with ZJW-6 enhanced the driving force of cellulose degradation. The acceleration of the rate of decomposition of straw releases nutrients that are easily absorbed by rice (Oryza sativa L.), providing favorable conditions for its growth and promoting its growth and development; prolongs the photosynthetic functioning period of leaves; and lays the material foundation for high yields of rice. ZJW-6 not only directly participates in cellulose degradation as degrading bacteria but also induces positive interactions between bacteria and fungi and enriches the microbial taxa that were related to straw degradation, enhancing the rate of rice straw degradation. Taken together, ZJW-6 has important biological potential and should be further studied, which will provide new insights and strategies for the appropriate treatment of rice straw. In the future, this degrading bacteria may provide a better opportunity to manage straw in an ecofriendly manner.


Assuntos
Bactérias , Oryza , Microbiologia do Solo , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Caules de Planta/microbiologia , Caules de Planta/metabolismo , Celulose/metabolismo , Biodegradação Ambiental , Agricultura/métodos , Solo/química
4.
J Sci Food Agric ; 104(4): 1897-1908, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37922382

RESUMO

BACKGROUND: Dry cultivation of rice is a water-saving, emission reduction and labor-saving rice farming method. However, the development of rice under dry cultivation is hampered by the limitations of dry cultivation on rice yield and rice quality. We hypothesized that additional silicon (Si) would be a measure to address these limitations or challenges. RESULTS: In the present study, we set up field trials with three treatments: flooded cultivation (W), dry cultivation (D) and dry cultivation plus Si. Yield and quality were reduced under D treatment compared to W treatment. The addition of Si promoted root development, increased plant height and leaf area, increased photosynthetic enzyme activity, net photosynthetic rate and SPAD values, and increased biomass under dry crop conditions. Under the drought conditions, silica up-regulated the expression of AGPSI, SBEI, SBEIIb, SSI and SSII-1 genes and the activities of ADP-glucose pyrophosphorylase (AGPase), soluble starch synthetase (SSS) and starch branching enzyme (SBE) enzymes, which reduced protein, amylose, chalkiness percentage and chalkiness degree, increased brown rice rate, milled rice rate and head milled rice rate, and also improved rice quality. In addition, the increase of AGPase, SSS and SBE enzyme activities promoted the filling rate and the number of spikes was guaranteed, whereas the yield was improved by promoting the seed setting rate and 1000-grain weight. CONCLUSION: The results of the present study indicate that adding appropriate amounts of Si fertilizer can improve the yield and quality of rice under dry cultivation by regulating source supply capacity and grain starch synthesis. © 2023 Society of Chemical Industry.


Assuntos
Oryza , Oryza/metabolismo , Silício/metabolismo , Amido/metabolismo , Amilose/metabolismo , Sementes/metabolismo
5.
Cancer Immunol Immunother ; 72(2): 493-507, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35963895

RESUMO

High rates of relapse and poor prognosis confer an urgent need for novel therapeutic agents for B cell non-Hodgkin lymphomas (B-NHLs). Herein, we describe a human IgG-like anti-CD79b/CD3 bispecific antibody (IBI38D9-L) that selectively depletes antigen-positive malignant B cells as an alternative treatment option for relapsed or refractory NHL patients. The antitumor activity and mechanism of action of IBI38D9-L were investigated in vitro using B-NHL cell lines and human primary effector cells and in vivo using xenograft models reconstituted with human PBMCs (peripheral blood mononuclear cells). Pharmacokinetic (PK) properties and preclinical toxicology were evaluated in cynomolgus monkeys and HSC-NPG mice. IBI38D9-L exerted potent B cell killing as well as T cell activation and proliferation in a tumor cell-dependent manner in vitro and was active against B-NHL cell lines with various CD79b expression levels. Subcutaneous xenograft tumors in NOG mice engrafted with human PBMCs were eradicated by IBI38D9-L treatment. Moreover, IBI38D9-L-treated mice showed a strong infiltration of activated T cells. In HSC-NPG mice, IBI38D9-L resulted in potent B cell depletion in peripheral blood and induced only slight body weight loss and cytokine release syndrome without significant toxicological findings. In cynomolgus monkeys, IBI38D9-L was well tolerated with good pharmacokinetic profiles. Collectively, these preclinical efficacy and safety data provide strong scientific rationales for using anti-CD79b/CD3 bispecific antibody as a promising therapeutic agent for B cell malignancies.


Assuntos
Anticorpos Biespecíficos , Neoplasias , Humanos , Camundongos , Animais , Macaca fascicularis , Leucócitos Mononucleares , Anticorpos Biespecíficos/farmacologia , Linfócitos B , Neoplasias/metabolismo , Complexo CD3
6.
Plant Cell Environ ; 46(4): 1363-1383, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36658612

RESUMO

Low-light stress compromises photosynthetic and energy efficiency and leads to spikelet sterility; however, the effect of low-light stress on pollen tube elongation in the pistil remains poorly understood. The gene RGA1, which encodes a Gα-subunit of the heterotrimeric G-protein, enhanced low-light tolerance at anthesis by preventing the cessation of pollen tube elongation in the pistil of rice plants. In this process, marked increases in the activities of acid invertase (INV), sucrose synthase (SUS) and mitochondrial respiratory electron transport chain complexes, as well as the relative expression levels of SUTs (sucrose transporter), SWEETs (sugars will eventually be exported transporters), SUSs, INVs, CINs (cell-wall INV 1), SnRK1A (sucrose-nonfermenting 1-related kinase 1) and SnRK1B, were observed in OE-1 plants. Accordingly, notable increases in contents of ATP and ATPase were presented in OE-1 plants under low-light conditions, while they were decreased in d1 plants. Importantly, INV and ATPase activators (sucrose and Na2 SO3 , respectively) increased spikelet fertility by improving the energy status in the pistil under low-light conditions, and the ATPase inhibitor Na2 VO4 induced spikelet sterility and decreased ATPase activity. These results suggest that RGA1 could alleviate the low-light stress-induced impairment of pollen tube elongation to increase spikelet fertility by promoting sucrose unloading in the pistil and improving the metabolism and allocation of energy.


Assuntos
Infertilidade , Oryza , Açúcares/metabolismo , Tubo Polínico , Plantas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Sacarose/metabolismo , Adenosina Trifosfatases/metabolismo , Oryza/genética
7.
Opt Express ; 31(20): 31670, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37858986

RESUMO

The referenced article [Opt. Express30, 36489 (2022)10.1364/OE.470330] has been retracted by the authors.

8.
Int J Mol Sci ; 24(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37446294

RESUMO

Phosphorus is an essential macronutrient for plant growth and development, but phosphate resources are limited and rapidly depleting due to massive global agricultural demand. This study identified two genes in the phosphate transporter 2 (PHT2) family of soybean by bioinformatics. The expression patterns of two genes by qRT-PCR at leaves and all were induced by low-phosphate stress. After low-phosphate stress, GmPHT2;2 expression was significantly higher than GmPHT2;1, and the same trend was observed throughout the reproductive period. The result of heterologous expression of GmPHT2 in Arabidopsis knockout mutants of atpht2;1 shows that chloroplasts and whole-plant phosphorus content were significantly higher in plants complementation of GmPHT2;2 than in plants complementation of GmPHT2;1. This suggests that GmPHT2;2 may play a more important role in plant phosphorus metabolic homeostasis during low-phosphate stress than GmPHT2;1. In the yeast backfill assay, both genes were able to backfill the ability of the defective yeast to utilize phosphorus. GmPHT2 expression was up-regulated by a low-temperature treatment at 4 °C, implying that GmPHT2;1 may play a role in soybean response to low-temperature stress, in addition to being involved in phosphorus transport processes. GmPHT2;1 and GmPHT2;2 exhibit a cyclic pattern of circadian variation in response to light, with the same pattern of gene expression changes under red, blue, and white light conditions. GmPHT2 protein was found in the chloroplast, according to subcellular localization analysis. We conclude that GmPHT2 is a typical phosphate transporter gene that can improve plant acquisition efficiency.


Assuntos
Arabidopsis , Proteínas de Transporte de Fosfato , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Glycine max/metabolismo , Saccharomyces cerevisiae/metabolismo , Fosfatos/metabolismo , Fósforo/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/metabolismo , Proteínas de Plantas/metabolismo
9.
Cancer Immunol Immunother ; 71(2): 353-363, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34165607

RESUMO

CD47 is a widely expressed cell-surface protein that regulates phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate immune cells, signal regulatory protein (SIRP)-α, which in turn inhibits phagocytosis. Several targeted CD47 therapeutic antibodies have been investigated clinically; however, how to improve its therapeutic efficacy remains unclear. Herein, we developed a CD47 blocking antibody, named IBI188, that could specifically block the CD47-SIRP-α axis, which transduces the "don't eat me" signal to macrophages. In vitro phagocytosis assays demonstrated the pro-phagocytosis ability of IBI188. Furthermore, several in vivo models were chosen to evaluate the anti-tumor efficacy of IBI188. IBI188 treatment upregulated cell movement- and inflammation-related genes in macrophages. Synergism was observed when combined with an anti-CD20 therapeutic antibody, whose function depends on antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno CD47/antagonistas & inibidores , Imunoterapia/métodos , Linfoma de Células B/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Apoptose , Antígeno CD47/imunologia , Proliferação de Células , Feminino , Humanos , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/imunologia , Neoplasias/patologia , Fagocitose , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Opt Express ; 30(20): 36489-36499, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258576

RESUMO

Multispectral optoacoustic tomography (MSOT) has become the dominant technical solution for photoacoustic imaging (PAI). However, the laser source of fiber output in the current MSOT method is typically a TEM00 Gaussian beam, which is prone to artifacts and incomplete due to the uneven distribution of the irradiated light intensity. Here, we propose a novel method to improve the quality of photoacoustic image reconstruction by modulating the wavefront shaping of the incident laser beam based on the designed scattering structure. In the experiment, we add the designed scattering structure to the current hemispherical photoacoustic transducer array device. Through experiments and simulations, we investigate and compare the effects of different scattering structures on laser intensity modulation. The results show that an ED1-C20 diffusion structure with a scattering angle of 20 degrees has the most effective modulation of the beam intensity distribution. And we choose gold nanoparticles of 50-100 nanometers (nm) diameters and index finger capillary vessels respectively as the medium of PAI. We obtain the highest ratio of PAI area increases of gold nanoparticles and index finger to devices compare without scattering structure is 29.69% and 634.94%, respectively. Experimental results demonstrate that our method is significantly higher quality than traditional methods, which has great potential for theoretical application in medical PAI.

11.
Opt Express ; 30(18): 32937-32947, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242345

RESUMO

Metasurface with metal-insulator-metal (MIM) structure has absorption properties for incident light at specific wavelengths. In this paper, we propose an infrared metasurface absorber based on silicon-based complementary metal oxide semiconductor (CMOS) process. By adding the prepared infrared metasurface absorber to the liquid crystal on silicon (LCoS) chip, it is used as the absorbing layer of LCoS configured between the pixel unit and the CMOS driver circuit. The effect of zero-order light caused by the gap between pixels in LCoS spatial light modulator (LCoS-SLM) on the light modulation function of the device is effectively reduced. Experiments show that the LCoS-SLM with infrared metasurface absorption structure can eliminate the zero-order light interference between the pixel gaps to a great extent and improve the modulation efficiency of the device. The proposed LCoS-SLM integrating infrared metasurface absorber structure based on silicon-based CMOS process has the advantages of low-cost and high modulation efficiency, which has high application value in the fields of holographic display, optical computing and optical communication.

12.
Arch Microbiol ; 204(2): 139, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032191

RESUMO

In the present study, 27 bacterial strains were isolated from environmental samples and screened for higher lignocellulose-degrading efficiency. The best degrader was combined in pairs with 14 strains with high ß-glucosidase activity to formulate a consortium. Microbial consortium 625 showed high lignocellulose degradation efficiency. ZJW-6 with low ß-glucosidase activity and the best lignocellulose decomposer was identified as a member of Cellulomonas. Consortium 625 composed of ZJW-6 and DA-25, an Acinetobacter, showed the highest degradation rate (57.62%) under optimized conditions. The DA-25 filtrate promoted ZJW-6 growth, upregulating the activity of key lignocellulose-degrading enzymes, including ß-glucosidase, endoglucanase, xylanase, laccase, and lignin peroxidase. ZJW-6 and DA-25 worked in a subordination manner when co-cultivated. ZJW-6 acted as the major decomposer whose growth and enzymatic activities were promoted by DA-25. This study proposes a novel microbial consortium with improved lignocellulose degradation efficiency and reduce the C:N ratio of lignocellulose materials, which can enhance bioenergy production.


Assuntos
Acinetobacter , Cellulomonas , Lignina , Consórcios Microbianos
13.
Plant Mol Biol ; 105(4-5): 451-462, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387174

RESUMO

KEY MESSAGE: The relative position of domains is critical for enzymatic properties of tau class glutathione S-transferases, and altering the position of linker far away from the active center affects catalytic property. Glutathione S-transferases (GSTs) are a family of phase II detoxification enzymes whose main function is to improve plant resistance to stresses. To understand the structural effects of tau class GSTs on their function, using OsGSTU17 as an example, we predicted the residues involved in the interactions between its domains and linker region. We further detected the structural changes in mutants and the corresponding changes in terms of substrate activity and kinetic parameters. Four pairs of residues, including Ala14 and Trp165, Arg20 and Tyr154, Glu74 and Arg98, Asp77 and Met87, forming hydrogen bonds and salt bridges were found to play important roles in maintaining the relative position between the domains and linker region inside the protein. The hydrogen bond between Trp165 and Ala14 affected the structural stability has been demonstrated in our previous study. The mutant R20A lost almost all catalytic activity. Interestingly, the mutant E74A exhibited a significant decrease in activity towards 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole, 1-chloro-2, 4-dinitrobenzene and 4-nitrobenzyl chloride, while its activity towards substrate cumene hydroperoxide remained unchanged. Compared with other mutants, the mutant D77A exhibited decreased affinity to its substrates and increased activity towards 1-chloro-2, 4-dinitrobenzene and cumene hydroperoxide, but its thermodynamic stability did not change significantly. The relative position of individual domain was critical for enzymatic properties, and the linker which is far away from the active site could change the enzymatic properties of GSTs via altering the relative position of the individual domain. Our results provide insights into the relationship between structure and function of tau class GSTs.


Assuntos
Aminoácidos/genética , Domínio Catalítico , Glutationa Transferase/genética , Oryza/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Aminoácidos/química , Aminoácidos/metabolismo , Arginina/química , Arginina/genética , Arginina/metabolismo , Ácido Aspártico/química , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Estabilidade Enzimática/genética , Ácido Glutâmico/química , Ácido Glutâmico/genética , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Modelos Moleculares , Mutação , Oryza/enzimologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Especificidade por Substrato
14.
Cancer Immunol Immunother ; 70(2): 365-376, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32761423

RESUMO

CD47, an immune checkpoint receptor frequently unregulated in various blood and solid tumors, interacts with ligand SIPRα on innate immune cells, and conveys a "do not eat me" signal to inhibit macrophage-mediated tumor phagocytosis. This makes CD47 a valuable target for cancer immunotherapy. However, the therapeutic utility of CD47-SIRPα blockade monoclonal antibodies is largely compromised due to significant red blood cell (RBCs) toxicities and fast target-mediated clearance as a result of extensive expression of CD47 on normal cells. To overcome these limitations and further improve therapeutic efficacy, we designed IBI322, a CD47/PD-L1 bispecific antibody which attenuated CD47 activity in monovalent binding and blocked PD-L1 activity in bivalent binding. IBI322 selectively bound to CD47+PD-L1+ tumor cells, effectively inhibited CD47-SIRPα signal and triggered strong tumor cell phagocytosis in vitro, but only with minimal impact on CD47 single positive cells such as human RBCs. In addition, as a dual blocker of innate and adaptive immune checkpoints, IBI322 effectively accumulated in PD-L1-positive tumors and demonstrated synergistic activity in inducing complete tumor regression in vivo. Furthermore, IBI322 showed only marginal RBCs depletion and was well tolerated in non-human primates (NHP) after repeated weekly injections, suggesting a sufficient therapeutic window in future clinical development of IBI322 for cancer treatment.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/uso terapêutico , Antígeno CD47/antagonistas & inibidores , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Animais , Anticorpos Biespecíficos/farmacologia , Antígeno B7-H1/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Neoplasias/patologia
15.
Opt Express ; 29(7): 10465-10470, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33820180

RESUMO

Transmissive metasurfaces formed by high-index dielectric materials have received great attention due to its potential in holograms, deflectors, beam converters, and flat lenses. However, a key challenge of all-dielectric metasurfaces is the limited scale and high cost in fabrication, such as electron beam lithography (EBL) and focused ion beam (FIB) lithography. In this paper, for the first time to our knowledge, an anodized aluminum oxide (AAO) template is combined with titanium dioxide (TiO2) metasurface fabrication with advantages of large area (>2cm2) and low cost. Using the ordered anodized aluminum oxide (AAO) as an evaporation mask, a TiO2 nanocylinder array is deposited through the AAO mask onto the SiO2 substrate. Electric and magnetic dipole resonances of TiO2 metasurface appear in the visible spectrum. Furthermore, we demonstrate the interaction of the CsPbBr1.5I1.5 quantum dot (QD) emission with magnetic dipole (MD) resonance of TiO2 metasurface. Our results reveal that the metasurface exhibits remarkable photoluminescence (PL) enhancement of 25%. Up to now, a TiO2 metasurface with 2.25-cm2-large area using AAO template method has never been attempted. Different from the metasurfaces fabricated by FIB and EBL, our method offers great ease for large-area metasurface fabrication, which is convenient for metasurface researchers and avoids costly facilities.

16.
Cancer Immunol Immunother ; 69(6): 939-950, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32078015

RESUMO

With the great success of anti-CTLA-4 and anti-PD-1 therapeutics in cancer immunotherapy, tumor necrosis factor receptor superfamily members have been recognized as ideal targets to provide co-stimulatory signals in combination with immune checkpoint blocking antibodies. Among these is OX40 (CD134), a co-stimulatory molecule expressed by activated immune cells. Recently, several anti-OX40 agonistic monoclonal antibodies, pogalizumab as the most advanced, have entered early phase clinical trials. Using a yeast platform and multiple screening methods, we identified a fully human anti-OX40 antibody (IBI101) with distinct modes of action. Unlike pogalizumab, IBI101 partially blocks the binding of OX40 to its ligand OX40L and exhibits both FcγR-dependent and independent agonistic activities in NF-κB luciferase reporter assays. IBI101 also promotes T cell activation and proliferation in vitro. These unique properties partially explain the more potent anti-tumor activity of IBI101 than that of pogalizumab in humanized NOG mice bearing LoVo tumors. In addition, IBI101 shows efficacious anti-tumor activity in mice when administrated alone or in combination with anti-PD-1 antibodies. In human OX40 knock-in mice bearing MC38 colon carcinoma, IBI101 treatment induces tumor antigen-specific CD8+ T-cell responses, decreases immunosuppressive regulatory T cells in tumor, and enhances the immune response to PD-1 inhibition. Preclinical studies of IBI101 in non-human primates demonstrate typical pharmacokinetic characteristics of an IgG antibody and no drug-related toxicity. Collectively, IBI101 has desirable preclinical attributes which support its clinical development for cancer treatment.


Assuntos
Imunoterapia/métodos , Receptores OX40/imunologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Camundongos
17.
Sensors (Basel) ; 17(7)2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28672867

RESUMO

Predicting large-scale transportation network traffic has become an important and challenging topic in recent decades. Inspired by the domain knowledge of motion prediction, in which the future motion of an object can be predicted based on previous scenes, we propose a network grid representation method that can retain the fine-scale structure of a transportation network. Network-wide traffic speeds are converted into a series of static images and input into a novel deep architecture, namely, spatiotemporal recurrent convolutional networks (SRCNs), for traffic forecasting. The proposed SRCNs inherit the advantages of deep convolutional neural networks (DCNNs) and long short-term memory (LSTM) neural networks. The spatial dependencies of network-wide traffic can be captured by DCNNs, and the temporal dynamics can be learned by LSTMs. An experiment on a Beijing transportation network with 278 links demonstrates that SRCNs outperform other deep learning-based algorithms in both short-term and long-term traffic prediction.

18.
Wei Sheng Wu Xue Bao ; 56(4): 651-63, 2016 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-29717855

RESUMO

Objective: To identify the function of glucose dehydrogenase (GDH) and gene expression level in the process of solubilizing phosphorus. Methods: Phosphate solubilizing bacteria (PSB) were isolated and purified by soluble phosphorus circle method, and identified by Vitek 2 system and 16S rRNA sequence. The phosphate solubilization capacity and GDH activity of PSB were determined. GDH genes were cloned by PCR and the relative expression level of both genes under different conditions were determined by real-time quantitative PCR. Results: Two PSB were identified as Pseudomonas sp. and Enterobacter sp. and the highest phosphorus solubilizing capability was 558 µg/mL for the former and 478 µg/mL for the latter. GDH genes of the two bacteria were cloned and the fragments were 2007 bp and 2066 bp. Different GDH activity and GDH gene expression were cultivated under the condition of different phosphorus sources and pH value. GDH gene expression of strain wj1 was higher than the other under high phosphorus, and the result was opposite under phosphorus stress. However, GDH gene expression of strain wj3 was lower in all phosphorus levels. The expression of GDH gene and the change of the enzyme activity were not obviously related with phosphorus solubilizing capability for strain wj3. Conclusion: There were different characteristics of GDH activity and GDH gene expression in two isolated strains that have different phosphate solubilizing mechanisms.


Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Proteínas de Bactérias/genética , Glucose 1-Desidrogenase/genética , Fósforo/metabolismo , Bactérias/enzimologia , Bactérias/genética , Proteínas de Bactérias/metabolismo , Expressão Gênica , Glucose 1-Desidrogenase/metabolismo , Concentração de Íons de Hidrogênio , Fosfatos/metabolismo , Filogenia , Microbiologia do Solo , Solubilidade
19.
Artigo em Inglês | MEDLINE | ID: mdl-39068602

RESUMO

VO2 with its special tunnel structure and high theoretical capacity is an ideal candidate for cathode materials for aqueous zinc-ion batteries (ZIBs). However, the slow kinetics and structural instability due to the strong electrostatic interactions between the host structure of VO2 and Zn2+ hinder its application. Defect engineering is a well-recognized strategy for improving the intrinsic ion-electron dynamics and structural stability of this material. However, the preparation of oxygen vacancies poses significant difficulties, and it is challenging to control their concentration effectively. Excessive or insufficient vacancy concentration can have a negative effect on the cathode material. Herein, we propose electrode materials with controlled oxygen vacancies prepared in situ on carbon nanofibers (CNF) by a simple, one-step hydrothermal process (Ov-VO2@CNF). This method can balance the adsorption energy and migration energy barrier easily, and we maximized the adsorption energy of Zn2+ while minimizing the adsorption energy barrier. Notably, the Ov2-VO2@CNF electrode delivered a high specific capacity (over 450 mAh g-1 at 0.1 A g-1) and excellent cycle stability (318 mAh g-1 at 5 A g-1 capacity after 2000 cycles with a capacity retention of 85%). This rational design of precisely regulated defect engineering provides a way to obtain advanced electrode materials with excellent comprehensive properties.

20.
Front Pharmacol ; 15: 1337179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974037

RESUMO

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

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