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1.
Cancer Immunol Immunother ; 73(5): 81, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38554184

RESUMEN

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.


Asunto(s)
Células Asesinas Naturales , Neoplasias , Humanos , Ligandos , Inmunoterapia , Linfocitos Infiltrantes de Tumor , Neoplasias/metabolismo
2.
Small ; : e2312006, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38431945

RESUMEN

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.
J Sci Food Agric ; 104(4): 1897-1908, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-37922382

RESUMEN

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.


Asunto(s)
Oryza , Oryza/metabolismo , Silicio/metabolismo , Almidón/metabolismo , Amilosa/metabolismo , Semillas/metabolismo
4.
Cancer Immunol Immunother ; 72(2): 493-507, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35963895

RESUMEN

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.


Asunto(s)
Anticuerpos Biespecíficos , Neoplasias , Humanos , Ratones , Animales , Macaca fascicularis , Leucocitos Mononucleares , Anticuerpos Biespecíficos/farmacología , Linfocitos B , Neoplasias/metabolismo , Complejo CD3
5.
Plant Cell Environ ; 46(4): 1363-1383, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36658612

RESUMEN

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.


Asunto(s)
Infertilidad , Oryza , Azúcares/metabolismo , Tubo Polínico , Plantas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Sacarosa/metabolismo , Adenosina Trifosfatasas/metabolismo , Oryza/genética
6.
Opt Express ; 31(20): 31670, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37858986

RESUMEN

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 Express30, 36489 (2022)10.1364/OE.470330] has been retracted by the authors.

7.
Int J Mol Sci ; 24(13)2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37446294

RESUMEN

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.


Asunto(s)
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 , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/metabolismo , Proteínas de Plantas/metabolismo
8.
Cancer Immunol Immunother ; 71(2): 353-363, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34165607

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígeno CD47/antagonistas & inhibidores , Inmunoterapia/métodos , Linfoma de Células B/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Animales , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Apoptosis , Antígeno CD47/inmunología , Proliferación Celular , Femenino , Humanos , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Neoplasias/inmunología , Neoplasias/patología , Fagocitosis , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Opt Express ; 30(18): 32937-32947, 2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36242345

RESUMEN

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.

10.
Opt Express ; 30(20): 36489-36499, 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36258576

RESUMEN

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.
Arch Microbiol ; 204(2): 139, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35032191

RESUMEN

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.


Asunto(s)
Acinetobacter , Cellulomonas , Lignina , Consorcios Microbianos
12.
Plant Mol Biol ; 105(4-5): 451-462, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33387174

RESUMEN

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.


Asunto(s)
Aminoácidos/genética , Dominio Catalítico , Glutatión Transferasa/genética , Oryza/genética , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Aminoácidos/química , Aminoácidos/metabolismo , Arginina/química , Arginina/genética , Arginina/metabolismo , Ácido Aspártico/química , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Estabilidad de Enzimas/genética , Ácido Glutámico/química , Ácido Glutámico/genética , Ácido Glutámico/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Modelos Moleculares , Mutación , Oryza/enzimología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Dominios Proteicos , Homología de Secuencia de Aminoácido , Especificidad por Sustrato
13.
Cancer Immunol Immunother ; 70(2): 365-376, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32761423

RESUMEN

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.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antígeno B7-H1/uso terapéutico , Antígeno CD47/antagonistas & inhibidores , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Animales , Anticuerpos Biespecíficos/farmacología , Antígeno B7-H1/farmacología , Humanos , Ratones , Ratones Endogámicos NOD , Neoplasias/patología
14.
Opt Express ; 29(7): 10465-10470, 2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33820180

RESUMEN

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.

15.
Cancer Immunol Immunother ; 69(6): 939-950, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32078015

RESUMEN

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.


Asunto(s)
Inmunoterapia/métodos , Receptores OX40/inmunología , Animales , Línea Celular , Modelos Animales de Enfermedad , Humanos , Ratones
16.
Sensors (Basel) ; 17(7)2017 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-28672867

RESUMEN

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.

17.
Wei Sheng Wu Xue Bao ; 56(4): 651-63, 2016 Apr 14.
Artículo en Zh | MEDLINE | ID: mdl-29717855

RESUMEN

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.


Asunto(s)
Bacterias/aislamiento & purificación , Bacterias/metabolismo , Proteínas Bacterianas/genética , Glucosa 1-Deshidrogenasa/genética , Fósforo/metabolismo , Bacterias/enzimología , Bacterias/genética , Proteínas Bacterianas/metabolismo , Expresión Génica , Glucosa 1-Deshidrogenasa/metabolismo , Concentración de Iones de Hidrógeno , Fosfatos/metabolismo , Filogenia , Microbiología del Suelo , Solubilidad
18.
J Chromatogr A ; 1708: 464367, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37714014

RESUMEN

Chirality is a common phenomenon in nature. Different enantiomers of chiral drug compounds have obvious differences in their effects on the human body. Therefore, the separation of chiral drugs plays an extremely important role in the safe utilization of drugs. High-performance liquid chromatography (HPLC) is an effective tool for the separation and analysis of compounds, in which the chromatographic packing plays a key role in the separation. Chiral pharmaceutical separation and analysis in HPLC rely on chiral stationary phases (CSPs). Thus, various CSPs are being developed to meet the needs of chiral drug separation and analysis. In this review, recent developments in CSPs, including saccharides (cyclodextrin, cellulose, amylose and chitosan), macrocycles (macrocyclic glycopeptides, pillar[n]arene and polyamide) and porous organic materials (metal-organic frameworks, covalent organic frameworks, and porous organic cages), for pharmaceutical analysis in HPLC were summarized, the advantages and disadvantages of various stationary phases were introduced, and their development prospects were discussed.


Asunto(s)
Amilosa , Estructuras Metalorgánicas , Humanos , Cromatografía Liquida , Cromatografía Líquida de Alta Presión , Celulosa , Preparaciones Farmacéuticas
19.
ACS Omega ; 8(50): 48081-48090, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38144091

RESUMEN

Allergic asthma is a prevalent form of asthma that is characterized primarily by airway inflammation. Jiegeng decoction (JGT) is a traditional Chinese herbal formula known for its anti-inflammatory properties and has been used to treat respiratory diseases for centuries. This study aimed to investigate the biological effects and mechanisms of action of JGT in improving allergic asthma. An experimental allergic asthma mouse model was established using ovalbumin. The results showed that JGT significantly improved inflammation cell infiltration in the lung tissue of allergic asthmatic mice and the inflammatory environment of Th2 cells in the bronchoalveolar lavage fluid while also reducing serum IgE levels. Subsequently, 38 components of JGT were identified through liquid chromatography-mass spectrometry. Network pharmacology revealed that regulating inflammation and immune responses is the primary biological process by which JGT improves allergic asthma, with Th2 cell differentiation and the JAK-STAT signaling pathway being the key mechanisms of action. Finally, qPCR, flow cytometry, and Western blotting were used to validate that JGT inhibited Th2 cell differentiation by blocking the JAK1-STAT6 signaling pathway in CD4+ T cells, ultimately improving allergic asthma. This study provides a novel perspective on the therapeutic potential of JGT in the treatment of allergic asthma.

20.
Genes (Basel) ; 14(8)2023 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-37628608

RESUMEN

Salt stress is an important environmental factor affecting crop growth and development. One of the important ways to improve the salt tolerance of rice is to identify new salt-tolerance genes, reveal possible mechanisms, and apply them to the creation of new germplasm and the breeding of new varieties. In this study, the salt-sensitive japonica variety Tong 35 (T35) and salt-tolerant japonica variety Ji Nongda 709 (JND709) were used. Salt stress treatment with a 150 mmol/L NaCl solution (the control group was tested without salt stress treatment simultaneously) was continued until the test material was collected after the rice germination period. Twelve cDNA libraries were constructed, and 5 comparator groups were established for transcriptome sequencing. On average, 9.57G of raw sequencing data were generated per sample, with alignment to the reference genome above 96.88% and alignment to guanine-cytosine (GC) content above 53.86%. A total of 16,829 differentially expressed genes were present in the five comparison groups, of which 2390 genes were specifically expressed in T35 (category 1), 3306 genes were specifically expressed in JND709 (category 2), and 1708 genes were differentially expressed in both breeds (category 3). Differentially expressed genes were subjected to gene ontology (GO), functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, which revealed that these genes belonged to three main classes: molecular function, cellular components, and biological processes. KEGG pathway analysis showed that the significantly enriched pathways for these differentially expressed genes included phenylpropane biosynthesis, phytohormone signaling, and the interaction of plants with pathogens. In this study, we provided a reference for studying the molecular mechanism underlying salt tolerance during germination.


Asunto(s)
Oryza , Tolerancia a la Sal , Tolerancia a la Sal/genética , Oryza/genética , Transcriptoma/genética , Fitomejoramiento , Estrés Salino
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