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Acute myeloid leukaemia (AML) is a fatal and refractory haematologic cancer that primarily affects adults. It interferes with bone marrow cell proliferation. Patients have a 5 years survival rate of less than 30% despite the availability of several treatments, including chemotherapy, allogeneic haematopoietic stem cell transplantation (Allo-HSCT), and receptor antagonist drugs. Allo-HSCT is the mainstay of acute myeloid leukaemia treatment. Although it does work, there are severe side effects, such as graft-versus-host disease (GVHD). In recent years, chimeric antigen receptor (CAR)-T cell therapies have made significant progress in the treatment of cancer. These engineered T cells can locate and recognize tumour cells in vivo and release a large number of effectors through immune action to effectively kill tumour cells. CAR-T cells are among the most effective cancer treatments because of this property. CAR-T cells have demonstrated positive therapeutic results in the treatment of acute myeloid leukaemia, according to numerous clinical investigations. This review highlights recent progress in new targets for AML immunotherapy, and the limitations, and difficulties of CAR-T therapy for AML.
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Imunoterapia Adotiva , Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , AnimaisRESUMO
The sensing sensitivity was improved for silver nanoparticles (AgNPs)-based colorimetric biosensors by using the most suitable salt to induce AgNPs aggregation. As for the salt composed of low-affinity anion and monovalent cation, the cation-dependent charge screening effect was the driving force for AgNPs aggregation. Apart from the charge screening effect, both the bridging of multivalent cation to the surface ligand of AgNP and the interaction between anion and Ag contributed to inducing AgNPs aggregation. Considering the higher aggregation efficiency of AgNPs resulted in a narrower sensing range, salt composed of low-affinity anion and monovalent cation was recommended for AgNPs-based colorimetric analysis, which was confirmed by fourfold higher sensitivity of DNA-21 detection using NaF than NaCl. This work inspires further thinking on improving the sensing performance of metal nanomaterials-based sensors from the point of colloidal surface science.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Cloreto de Sódio , Prata , Colorimetria/métodos , Ânions , Cátions MonovalentesRESUMO
CuCo2O4, a type of promising lithium-ion storage material, exhibits high electrochemical properties in lithium-ion batteries and enormous economic benefits. However, its practical application is limited by problems such as structural collapse and electrochemical stability during the charging and discharging process. In this work, the reduced graphene oxide (rGO)-coated CuCo2O4 (CuCo2O4/rGO) hollow microspheres were successfully prepared by electrostatic self-assembly. The CuCo2O4/rGO electrode shows an outstanding capability for lithium-ion storage and a remarkable rate capacity, e.g., 445 mA h g-1 at 5 A g-1. After 150 cycles at 0.1 A g-1, the reversible capacity of the CuCo2O4/rGO electrode is as high as 1080 mA h g-1, and it can still retain about 530 mA h g-1 in the 400th cycle at 1 A g-1. The hollow microspheres with mesoporous shells can cause electrolyte penetration into the spherical shell to effectively shorten the transfer distance of lithium ions, and the encapsulation of graphene improves the conductivity and stability of CuCo2O4, which endows CuCo2O4/rGO with a wonderful Li+ storage performance. It is proved that this is an efficient method to improve the electrochemical performance of metal compounds for better applications in energy storage.
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The controllable construction and function expansion of some sophisticated aggregations represent a current hot topic in scientific research. In this paper, using a prefabricated {Co14} cluster as a synthetic precursor, a homometallic {Co24} and a heterometallic {Co12Cd12} giant cluster possessing similar dual-[M12] (M = Co/Cd) skeletons was prepared by reacting the precursor with excess CoCl2 and Cd(OAc)2 salts, respectively. The detailed structural information on {Co24} and {Co12Cd12} was characterized by single-crystal X-ray diffraction and further analyzed by X-ray photoelectron spectroscopy, inductively coupled plasma-mass spectroscopy, and scanning electron microscopy with energy dispersive X-ray (EDX) spectroscopy in the solid state. Compared to the {Co14} precursor, magnetic difference revealed that spin-canting and magnetic ordering had been enhanced in {Co24} and suppressed in {Co12Cd12} when dotted with diamagnetic Cd2+ ions.
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With the motivation of controlling a magnetic switch by external stimuli, we report here an infinite chain structure formed from the secondary building units of Cu3Tb2 clusters through the linkage of nitrate ions. It behaves as a molecule-based magnet with the highest energy barrier among isolated Tb/Cu-based single-molecule magnets and single-chain magnets, which is close to a dimer of a Cu3Tb2 cluster unit from a magnetic point as revealed by its correlation length of 2.23 Cu3Tb2 units. This kind of molecule-based magnet in a chain structure is rare. The removal of its guest ethanol molecules leads to the complete disappearance of slow magnetic relaxation behavior. Interestingly, the capture and removal of guest ethanol molecules are reversible, mediating a rare ON/OFF switching of a 3d-4f heterometallic molecule-based magnet, which was interpreted by the theoretical calculations based on the structural difference upon desolvation.
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OBJECTIVE: This study aimed to comprehensively assess the characteristics and risk factors of hyperthyroidism with pulmonary hypertension (PH). METHODS: This was a retrospective cross-sectional analysis of 315 consecutive patients with hyperthyroidism admitted to the endocrinology department of Tongji Hospital from February 2016 to December 2017. PH was defined as a pulmonary arterial systolic pressure above 35 mm Hg measured by echocardiography. RESULTS: Among the 315 patients, 208 were females, the median age was 42 (30-51) years, and the median disease duration was 12 (3-48) months. Thirty-five percent (111/315) of patients were identified with PH. Patients with hyperthyroidism and PH showed significantly higher serum concentrations of free thyroxine (FT4), free triiodothyronine, thyroid receptor antibodies, total bilirubin (TB), direct and indirect bilirubin, lower serum levels of hemoglobin and creatinine, and more severe cardiac load (P < .05 for each) compared with patients without PH. Levels of serum FT4, free triiodothyronine, thyroid receptor antibodies, and thyroid peroxidase antibody were different among groups of patients with different levels of pulmonary arterial systolic pressure (P < .05 for each). Multivariate logistic regression analysis indicated that serum FT4 (odds ratio, 1.02; 95% CI, 1.01-1.04; P = .004) and TB (OR, 1.03; 95% CI, 1.00-1.06; P = .030) were independent risk factors for PH in patients with hyperthyroidism. CONCLUSION: Elevated serum FT4 and TB levels may be independent risk factors for PH in patients with hyperthyroidism and valuable indicators for the identification and treatment of patients with PH and hyperthyroidism.
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Hipertensão Pulmonar , Hipertireoidismo , Adulto , Estudos Transversais , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tireotropina , Tiroxina , Tri-IodotironinaRESUMO
It is known that the data acquisition and processing system plays an important role in radar target detection system. In order to meet the requirements of real-time processing and accurate transmission of echo signals in high-frequency ground-wave radar (HFGWR) systems, a new acquisition and transmission framework utilizing the designed acquisition card based on the PCIe (peripheral component interconnect express) has been designed and is presented in this paper. The Xilinx FPGA (Field-Programmable Gate Array) chip Kintex7-XC7K325T is adopted as a hardware carrier in acquisition card. The hardware's composition, analog front-end circuit, the DMA (Direct Memory Access) transmission, FPGA structure, ADC (Analog-to-Digital Converter) chip, and performance test of this card are showed and discussed. Currently, the acquisition card has been accomplished and applied in the practical system of HFGWR.
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INTRODUCTION: Depression, the most prevalent mood disorder, has high comorbidity with cerebrovascular disease and cognitive decline. However, there is little understanding of the cellular mechanisms involved in depression and its comorbid cerebrovascular damage and cognition impairment. Here, we tested the prediction that the chronic unpredictable mild stress (CUMS) mouse model would manifest in disturbed glymphatic function and that dietary supplementation with polyunsaturated fatty acids (PUFA) could ameliorate these deficits while alleviating the depression-associated cognitive decline. METHODS: To test the treatment effects of PUFA or Es on behaviours, we applied the tail suspension, open field, and sucrose preference tests to assess depressive symptoms, and applied the Morris water maze test to assess cognition in groups of control, chronic unpredictable mild stress (CUMS), PUFA, and escitalopram (Es) treatment. We measured the extracellular concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in microdialysates from prefrontal cortex (PFC) by liquid chromatography mass spectrometry. Glia cells and inflammatory factors were analysed with fluorescent immunochemistry and western blot, respectively. We tested brain vasomotor function with two-photon and laser speckle imaging in vivo, and measured glymphatic system function by two-photon imaging in vivo and fluorescence tracer imaging ex vivo, using awake and anesthetized mice. Besides, we monitored cortical spreading depression by laser speckle imaging system. AQP4 depolarization is analysed by fluorescent immunochemistry and western blot. RESULTS: We confirmed that CUMS elicited depression-like and amnestic symptoms, accompanied by decreased monoamines neurotransmitter concentration in PFC and upregulated neuroinflammation markers. Moreover, CUMS mice showed reduced arterial pulsation and compliance in brain, and exhibited depolarized expression of AQP4, thus indicating glymphatic dysfunction both in awake and anesthetized states. PUFA supplementation rescued depression-like behaviours of CUMS mice, reduced neuroinflammation and cerebrovascular dysfunction, ultimately improved cognitive performance, all of which accompanied by restoring glymphatic system function. In contrast, Es treatment alleviated only the depression-like behavioural symptoms, while showing no effects on glymphatic function and depression-incident cognitive deficits. CONCLUSIONS: The CUMS depression model entails suppression of the glymphatic system. PUFA supplementation rescued most behavioural signs of depression and the associated cognitive dysfunction by restoring the underlying glymphatic system disruption and protecting cerebral vascular function.
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Disfunção Cognitiva , Sistema Glinfático , Animais , Disfunção Cognitiva/tratamento farmacológico , Depressão/tratamento farmacológico , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Insaturados , Hipocampo , Camundongos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológicoRESUMO
AIMS: To establish a simple method to identify chemotherapy-induced liver injury among oncological patients. To evaluate current clinical approach to elevated laboratory liver test results. METHODS: A total of 289 patients admitted to oncology department who had systemic chemotherapy episodes for cancer treatment from 1 January 2017 to 31 December 2017 were identified. With aid of healthcare information system, Hy's law was applied to laboratory liver test results to identify potential hepatocellular drug-induced liver injury cases. Medical record review was carried out among identified patients to exclude liver dysfunction of alternative causes. Current clinical approach to elevated laboratory liver tests was evaluated through medical record review. RESULTS: Of 289 patients who were treated by systemic chemotherapies, there were 123 patients with elevated laboratory liver tests, among which 8 patients were suspected as potential Hy's law cases. After medical record review, there were two patients determined with chemotherapy-associated liver injury, caused by 5-fluorouracil, leucovorin, irinotecan, and S-1 plus paclitaxel separately. Of eight potential Hy's law cases, seven (87.5%) patients were prescribed with ≥2 kinds of liver protectants and remained treated with traditional Chinese medicine for decoction. CONCLUSIONS: A reliable and simple method to identify undiagnosed drug-induced liver injury was successfully established. An annual incidence of 0.69% of chemotherapy-associated liver injury in oncology department of the setting was found.
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Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Neoplasias/tratamento farmacológico , Assistência Farmacêutica/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Due to the motion of the platform, the spectrum of first-order sea clutter will widen and mask low-velocity targets such as ships in shipborne high-frequency surface-wave radar (HFSWR). Limited by the quantity of qualified training samples, the performance of the generally used clutter-suppression method, space-time adaptive processing (STAP) degrades in shipborne HFSWR. To deal with this problem, an innovative training sample acquisition method is proposed, in the area of joint domain localized (JDL) reduced-rank STAP. In this clutter-suppression method, based on a single range of cell data, the unscented transformation is introduced as a preprocessing step to obtain adequate homogeneous secondary data and roughly estimated clutter covariance matrix (CCM). The accurate CCM is calculated by integrating the approximate CCM of different range of cells. Compared with existing clutter-suppression algorithms for shipborne HFSWR, the proposed approach has a better signal-to-clutter-plus-noise ratio (SCNR) improvement tested by real data.
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An adaptive beamformer is sensitive to model mismatch, especially when the desired signal exists in the training samples. Focusing on the problem, this paper proposed a novel adaptive beamformer based on the interference-plus-noise covariance (INC) matrix reconstruction method, which is robust with gain-phase errors for uniform or sparse linear array. In this beamformer, the INC matrix is reconstructed by the estimated steering vector (SV) and the corresponding individual powers of the interference signals, as well as noise power. Firstly, a gain-phase errors model of the sensors is deduced based on the first-order Taylor series expansion. Secondly, sensor gain-phase errors, the directions of the interferences, and the desired signal can be accurately estimated by using an alternating descent method. Thirdly, the interferences and noise powers are estimated by solving a quadratic optimization problem. To reduce the computational complexity, we derive the closed-form solutions of the second and third steps with compressive sensing and total least squares methods. Simulation results and measured data demonstrate that the performance of the proposed beamformer is always close to the optimum, and outperforms other tested methods in the case of gain-phase errors.
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In order to maintain the stability of intracellular environment, various cells die autonomously in vivo, which is called apoptosis. As a key factor of cell apoptosis in the mitochondrial pathway, cytochrome c, somatic (CYCS) plays an important role in the process of male spermatogenesis. Based on more than 40 recent studies on CYCS by Chinese and foreign scholars, this review focuses on the involvement of CYCS in the mechanisms of the apoptosis and anti-apoptosis of germ cells and in the regulation of their quality and activity and also outlines the role of CYCS in marking male reproductive performance as well as in male infertility and its underlying mechanisms.
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Apoptose , Citocromos c/fisiologia , Células Germinativas/citologia , Espermatogênese , Humanos , Masculino , MitocôndriasRESUMO
Nuclear factor-κB (NF-κB) is an important regulatory factor in cells. NF-κB has a wide range of biological activities. After activation, it participates in the transcription and regulation of many genes and plays a role in infection, inflammatory response, oxidative stress, cell multiplication, and apoptosis. The activation of the NF-κB signal pathway is dependent on the degradation of the IκB kinase ß (IKKß) complex. IKK ß is the key kinase in the NF-κB activation pathway. After inhibition, it can block the activation of NF-κB. IKKß is a key regulator of NF-κB activation, also an early regulator of inflammation in all stages of the immune response. This study aimed to investigate the effect of IKKß-siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKß-siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKß-siRNA distribution in the liver was observed by immunofluorescence, and the quantitative polymerase chain reaction was used to detect inflammation-related and fibrosis-related factors. IKKß-siRNA lentiviruses could be delivered to the liver and significantly decrease carbon tetrachloride-induced hepatic fibrosis. Furthermore, serum transaminase levels significantly decreased, and inflammation-related and fibrosis-related factors decreased. IKKß-siRNA can be an effective method of anti-fibrosis gene therapy for liver fibrosis.
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Quinase I-kappa B , Cirrose Hepática , Interferência de RNA , Transdução de Sinais , Animais , Intoxicação por Tetracloreto de Carbono/genética , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Vetores Genéticos , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Lentivirus , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Masculino , RNA Interferente Pequeno/biossíntese , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução GenéticaRESUMO
To develop new lanthanide single-molecule magnets (SMMs), two new complexes of [Dy2(MeOH)2(HL1)2(NO3)2]·2MeOH (1) and [Dy6(µ3-OH)2(L2)2(HL2)2(H2L2)2Cl2(EtOH)2]Cl2·3EtOH·CH3CN (2) were obtained by reacting Dy(NO)3·6H2O with 3-amino-1,2-propanediol in the presence of 2-hydroxynaphthaldehyde for 1 and by reacting DyCl3·6H2O with 1,1-di(hydroxymethyl)ethylamine in the presence of 2-hydroxynaphthaldehyde for 2, respectively, in which the Schiff base ligands of 3-(((2-hydroxynaphthaen-1-yl)methylene)amino)-propane-1,2-diol (H3L1) and 2-(ß-naphthalideneamino)-2-(hydroxylmethyl)-1-propanol (H3L2) were in situ formed. The two Dy(III) ions in 1 are linked by two Oalkoxy atoms of two (HL1)2- ligands to build a dinuclear skeleton. Complex 2 presents a nearly planar hexanuclear skeleton constructed from four edge-shared triangular Dy3 units with the two peripheral Dy3 units consolidated by two µ3-O bridges and the two central Dy3 units consolidated by one µ3-O bridge. Obviously, they exhibit a different topological arrangement resulting from the linkage of the Schiff base ligands. Both of them are typical SMMs under zero dc fields, with a Ueff/ kB value of 34 K for 1 and 40 K for 2, respectively. Multiple processes are involved in the relaxation processes of 1 and 2. The different SMM performances of the two titled complexes reveal a tuning effect of Schiff base ligands through tuning the coordination environments and topological arrangements of dysprosium(III) ions, which is supported by the theoretical calculations.
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BACKGROUND/AIMS: Our previous studies demonstrated that a novel long non-coding RNA, CYP4B1-PS1-001, was significantly downregulated in early diabetic nephropathy in vivo and in vitro, and CYP4B1-PS1-001 overexpression could inhibit the proliferation and fibrosis of mouse mesangial cells (MMCs). However, the underlying mechanism of the CYP4B1-PS1-001-mediated regulation of proliferation and fibrosis in diabetic nephropathy remains undetermined. METHODS: RNA-protein pull-down assay, RNA-binding protein immunoprecipitation, and mass spectrometry were used to investigate CYP4B1-PS1-001 interacted with the upregulated protein nucleolin (NCL). siRNA method was applied to knockdown NCL in MMCs, the interaction between CYP4B1-PS1-001 and NCL were determined by Western blot analysis and RT-qPCR. The effect of CYP4B1-PS1-001 in the regulation of NCL was detected by cycloheximide (CHX) and ubiquitination assays. RESULTS: We found that CYP4B1-PS1-001 interacts with NCL, and CYP4B1-PS1-001 inhibits the proliferation and fibrosis of MMCs depending on interaction with NCL. Furthermore, degradation of CYP4B1-PS1-001-associated NCL was mediated by a ubiquitin proteasome-dependent pathway. CONCLUSION: Our study provides evidence that CYP4B1-PS1-001 regulates the ubiquitination and degradation of NCL and thereby plays a critical role in the proliferation and fibrosis of MMCs, indicating that CYP4B1-PS1-001 and NCL may be promising prognostic biomarkers and molecular targets for the treatment of diabetic nephropathy.
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Proliferação de Células , Fosfoproteínas/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Colágeno Tipo I/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/veterinária , Fibronectinas/metabolismo , Fibrose , Masculino , Células Mesangiais/citologia , Células Mesangiais/metabolismo , Camundongos , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ligação Proteica , Proteínas/antagonistas & inibidores , Proteínas/genética , Proteínas/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Ubiquitinação , NucleolinaRESUMO
We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co13(µ3-OH)3(µ3-Cl)(dpbt)5(ptd)Cl10][Co(H2O)2Cl2]·(CH3)2CHOH (1) and [Co24(µ3-OH)6(µ3-Cl)2(dpbt)10(ptd)2Cl16]·2CH3CH2OH (2), respectively (H2dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H2ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co4(µ3-OH)3(µ3-Cl)] cubane and an outer [Co9(dpbt)5(ptd)Cl10] defective adamantane. Compound 2 reveals a giant {Co24} cluster possessing a dual-[Co12] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).
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Manganese transport protein C (MntC) of Staphylococcus aureus represents an excellent vaccine-candidate antigen. The important role of CD4+ T cells in effective immunity against S. aureus infection was shown; however, CD4+ T cell-specific epitopes on S. aureus MntC have not been well identified. Here, we used bioinformatics prediction algorithms to evaluate and identify nine candidate epitopes within MntC. Our results showed that peptide M8 emulsified in Freund's adjuvant induced a much higher cell-proliferation rate as compared with controls. Additionally, CD4+ T cells stimulated with peptide M8 secreted significantly higher levels of interferon-γ and interleukin-17A. These results suggested that peptide M8 represented an H-2d (I-E)-restricted Th17-specific epitope.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/isolamento & purificação , Manganês/metabolismo , Proteína C/metabolismo , Staphylococcus aureus/imunologia , Staphylococcus aureus/metabolismo , Algoritmos , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Citocinas/metabolismo , Mapeamento de Epitopos , Escherichia coli/genética , Feminino , Interferon gama/metabolismo , Interleucina-17/metabolismo , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos BALB C , Proteína C/genética , Proteína C/imunologia , Estrutura Secundária de Proteína , Proteínas Recombinantes/imunologia , Infecções Estafilocócicas/imunologia , Células Th1/imunologia , Células Th17/imunologiaRESUMO
The GapC protein is highly conserved surface dehydrogenase among Streptococcus dysgalactiae (S. dysgalactiae) and is shown to be involved in bacterial virulence. Immunization of GapC protein can induce specific CD4(+) T-cell immune responses and protect against S. dysgalactiae infection. However, there are no studies to identify immunodominant CD4(+) T-cell epitopes on GapC protein. In this study, in silico MHC affinity measurement method was firstly used to predict potential CD4(+) T-cell epitopes on GapC protein. Six predictive 15-mer peptides were synthesized and two novel GapC CD4(+) T-cell epitopes, GapC63-77 and GapC96-110, were for the first time identified using CD4(+) T-cells obtained from GapC-immunized BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice spleen based on cell proliferation and cytokines response. The results showed that peptides containing 63-77 and 96-110 induced significant antigen-specific CD4(+) T-cells proliferation response in vivo. At the same time, high levels of IFN-γ and IL-17A, as well as moderate levels of IL-10 and IL-4 were detected in CD4(+) T-cells isolated from both GapC and peptide-immunized mice in vivo, suggesting that GapC63-77 and GapC96-110 preferentially elicited polarized Th1/Th17-type responses. The characterization of GapC CD4(+) T-cell epitopes not only helps us understand its protective immunity, but also contributes to design effective T-cell epitope-based vaccine against S. dysgalactiae infection.
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Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus/imunologia , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Mapeamento de Epitopos , Epitopos de Linfócito T/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologia , Streptococcus/genéticaRESUMO
To realize ground moving target indication (GMTI) for a forward-looking array, we propose a novel synthetic aperture radar (SAR) system, called rotatable cross-track interferometry SAR (Ro-XTI-SAR), for squint-looking application in this paper. By changing the angle of the cross-track baseline, the interferometry phase component of squint-looking Ro-XTI-SAR caused by the terrain height can be approximately adjusted to zero, and then the interferometry phase of Ro-XTI-SAR is only sensitive to targets' motion and can be equivalent to the along track interferometry SAR (ATI-SAR). Furthermore, the conventional displaced phase center array (DPCA) method and constant false alarm (CFAR) processing can be used to accomplish the successive clutter suppression, moving targets detection and relocation. Furthermore, the clutter suppressing performance is discussed with respect to different system parameters. Finally, some results of numerical experiments are provided to demonstrate the effectiveness of the proposed system.
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Iron-regulated surface determinant B (IsdB) of Staphylococcus aureus (S. aureus) is a highly conserved surface protein that can induce protective CD4(+) T-cell immune response. A pivotal role of CD4(+) T-cells in effective immunity against S. aureus infection has been proved, but CD4(+) T-cell epitopes on the S. aureus IsdB have not been well identified. In this study, MHC binding assay was firstly used to predict CD4(+) T-cell epitopes on S. aureus IsdB protein, and six peptides were synthesized to validate the probable epitopes. Two novel IsdB CD4(+) T-cell epitopes, P1 (residues 159-178) and P4 (residues 287-306), were for the first time identified using CD4(+) T-cells obtained from IsdB-immunized C57BL/6 (H-2(b)) and BALB/c (H-2(d)) mice spleen based on cell proliferation and cytokines response. The results showed that P1 and P4 emulsified in Freund's adjuvant (FA) induced much higher cell proliferation compared with PBS emulsified in FA. CD4(+) T-cells stimulated with peptides P1 and P4 secreted significantly higher levels of IFN-γ and IL-17A. However, the level of the cytokine IL-4 almost remained unchanged, suggesting that P1 and P4 preferentially elicited polarized Th1-type responses. In addition, BALB/c mice just respond to P4 not P1, while C57BL/6 mice respond to P1 not P4, implying that epitope P1 and P4 were determined as H-2(b) and H-2(d) restricted epitope, respectively. Taken together, our data may provide an explanation of the IsdB-induced protection against S. aureus and highlight the possibility of developing the epitope-based vaccine against the S. aureus.