Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
1.
Materials (Basel) ; 17(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38793340

RESUMO

Materials offering high energy density are currently desired to meet the increasing demand for energy storage applications, such as pulsed power devices, electric vehicles, high-frequency inverters, and so on. Particularly, ceramic-based dielectric materials have received significant attention for energy storage capacitor applications due to their outstanding properties of high power density, fast charge-discharge capabilities, and excellent temperature stability relative to batteries, electrochemical capacitors, and dielectric polymers. In this paper, we present fundamental concepts for energy storage in dielectrics, key parameters, and influence factors to enhance the energy storage performance, and we also summarize the recent progress of dielectrics, such as bulk ceramics (linear dielectrics, ferroelectrics, relaxor ferroelectrics, and anti-ferroelectrics), ceramic films, and multilayer ceramic capacitors. In addition, various strategies, such as chemical modification, grain refinement/microstructure, defect engineering, phase, local structure, domain evolution, layer thickness, stability, and electrical homogeneity, are focused on the structure-property relationship on the multiscale, which has been thoroughly addressed. Moreover, this review addresses the challenges and opportunities for future dielectric materials in energy storage capacitor applications. Overall, this review provides readers with a deeper understanding of the chemical composition, physical properties, and energy storage performance in this field of energy storage ceramic materials.

2.
Sci Rep ; 13(1): 22303, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102231

RESUMO

In this study, numerical simulation was employed to predict the performance and internal flow characteristics of the inlet of an axial-flow pump by assigning an absolute flow angle to the inlet guide vane (IGV) trailing-edge flow. Further, the finite volume method based on the three-dimensional Reynolds-averaged Navier-Stokes equations was employed to discretize the governing equations. The shear stress transport model was used as the turbulence model, and an appropriate number of nodes were selected for the hexahedral grid system through a grid-dependency test. The performance curve and changes in the internal flow field were investigated based on the variation in the flow angle at the inlet of the axial-flow pump. These results can be used to establish an efficient operational plan by adjusting the IGV angle of IGV when installing a variable IGV for an axial-flow pump.

3.
Micromachines (Basel) ; 14(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-38004839

RESUMO

In this study, we present the energy absorption capabilities achieved through the application of hybrid lattice structures, emphasizing their potential across various industrial sectors. Utilizing Ti-6Al-4V and powder bed fusion (PBF) techniques, we fabricated distinct octet truss, diamond, and diagonal lattice structures, tailoring each to specific densities such as 10, 30, and 50%. Furthermore, through the innovative layering of diverse lattice types, we introduced hybrid lattice structures that effectively overcome the inherent energy absorption limitations of single-lattice structures. As a result, we conducted a comprehensive comparison between single-lattice structures and hybrid lattice structures of equal density, unequivocally showcasing the latter's superior energy absorption performance in terms of compression. The single-lattice structure, OT, showed an energy absorption of 42.6 J/m3, while the reinforced hybrid lattice structure, OT-DM, represented an energy absorption of 77.8 J/m3. These findings demonstrate the significant potential of hybrid lattice structures, particularly in energy-intensive domains such as shock absorption structures. By adeptly integrating various lattice architectures and leveraging their collective energy dissipation properties, hybrid lattice structures offer a promising avenue for addressing energy absorption challenges across diverse industrial applications.

4.
J Immunother Cancer ; 11(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37848261

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a type of leukemia in adults with a high mortality rate and poor prognosis. Although targeted therapeutics, chemotherapy, and hematopoietic stem cell transplantation can improve the prognosis, the recurrence rate is still high, with a 5-year survival rate of approximately 40%. This study aimed to develop an IgG-based asymmetric bispecific antibody that targets CLL-1 and CD3 for treating AML. METHODS: ABL602 candidates were compared in terms of binding activity, T-cell activation, and tumor-killing activities. ABL602-mediated T-cell activation and tumor-killing activities were determined by measuring the expression of activation markers, cytokines, cytolytic proteins, and the proportion of dead cells. We evaluated in vivo tumor growth inhibitory activity in two mouse models bearing subcutaneously and orthotopically engrafted human AML. Direct tumor-killing activity and T-cell activation in patient-derived AML blasts were also evaluated. RESULTS: ABL602 2+1 showed a limited CD3 binding in the absence of CLL-1, suggesting that steric hindrance on the CD3 binding arm could reduce CLL-1 expression-independent CD3 binding. Although the CD3 binding activity was attenuated compared with that of 1+1, ABL602 2+1 exhibited much stronger T-cell activation and potent tumor-killing activities in AML cell lines. ABL602 2+1 efficiently inhibited tumor progression in subcutaneously and orthotopically engrafted AML mouse models. In the orthotopic mouse model, tumor growth inhibition was observed by gross measurement of luciferase activity, as well as a reduced proportion of AML blasts in the bone marrow, as determined by flow cytometry and immunohistochemistry (IHC) staining. ABL602 2+1 efficiently activated T cells and induced the lysis of AML blasts, even at very low effector:target (E:T) ratios (eg, 1:50). Compared with the reference 1+1 antibody, ABL602 did not induce the release of cytokines including interleukin-6 and tumor necrosis factor-α in the healthy donor-derived peripheral blood mononuclear cell. CONCLUSIONS: With its potent tumor-killing activity and reduced cytokine release, ABL602 2+1 is a promising candidate for treating patients with AML and warrants further study.


Assuntos
Anticorpos Biespecíficos , Leucemia Linfocítica Crônica de Células B , Leucemia Mieloide Aguda , Camundongos , Adulto , Animais , Humanos , Citocinas/metabolismo , Leucócitos Mononucleares , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico
5.
Materials (Basel) ; 16(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37895734

RESUMO

In this paper, we investigate the structural, microstructural, dielectric, and energy storage properties of Nd and Mn co-doped Ba0.7Sr0.3TiO3 [(Ba0.7Sr0.3)1-xNdxTi1-yMnyO3 (BSNTM) ceramics (x = 0, 0.005, and y = 0, 0.0025, 0.005, and 0.01)] via a defect dipole engineering method. The complex defect dipoles (MnTi"-VO∙∙)∙ and (MnTi"-VO∙∙) between acceptor ions and oxygen vacancies capture electrons, enhancing the breakdown electric field and energy storage performances. XRD, Raman, spectroscopy, XPS, and microscopic investigations of BSNTM ceramics revealed the formation of a tetragonal phase, oxygen vacancies, and a reduction in grain size with Mn dopant. The BSNTM ceramics with x = 0.005 and y = 0 exhibit a relative dielectric constant of 2058 and a loss tangent of 0.026 at 1 kHz. These values gradually decreased to 1876 and 0.019 for x = 0.005 and y = 0.01 due to the Mn2+ ions at the Ti4+- site, which facilitates the formation of oxygen vacancies, and prevents a decrease in Ti4+. In addition, the defect dipoles act as a driving force for depolarization to tailor the domain formation energy and domain wall energy, which provides a high difference between the maximum polarization of Pmax and remnant polarization of Pr (ΔP = 10.39 µC/cm2). Moreover, the complex defect dipoles with optimum oxygen vacancies in BSNTM ceramics can provide not only a high ΔP but also reduce grain size, which together improve the breakdown strength from 60.4 to 110.6 kV/cm, giving rise to a high energy storage density of 0.41 J/cm3 and high efficiency of 84.6% for x = 0.005 and y = 0.01. These findings demonstrate that defect dipole engineering is an effective method to enhance the energy storage performance of dielectrics for capacitor applications.

6.
Nanomicro Lett ; 15(1): 191, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532956

RESUMO

Porous 2D materials with high conductivity and large surface area have been proposed for potential electromagnetic interference (EMI) shielding materials in future mobility and wearable applications to prevent signal noise, transmission inaccuracy, system malfunction, and health hazards. Here, we report on the synthesis of lightweight and flexible flash-induced porous graphene (FPG) with excellent EMI shielding performance. The broad spectrum of pulsed flashlight induces photo-chemical and photo-thermal reactions in polyimide films, forming 5 × 10 cm2-size porous graphene with a hollow pillar structure in a few milliseconds. The resulting material demonstrated low density (0.0354 g cm-3) and outstanding absolute EMI shielding effectiveness of 1.12 × 105 dB cm2 g-1. The FPG was characterized via thorough material analyses, and its mechanical durability and flexibility were confirmed by a bending cycle test. Finally, the FPG was utilized in drone and wearable applications, showing effective EMI shielding performance for internal/external EMI in a drone radar system and reducing the specific absorption rate in the human body.

7.
Plants (Basel) ; 12(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37299087

RESUMO

Cudrania tricuspidata is a traditional medicinal herb in East Asia. The compounds of plants vary depending on environmental factors, such as soil, temperature, drainage, and so on. However, few to no studies have been done on the correlation among environment, growth, and compounds in C. tricuspidata. Thus, we aimed to investigate their relationship. Samples of C. tricuspidata fruit and cultivation soil were collected from 28 cultivation sites in October 2021. Six growth characteristics, eleven soil physicochemical properties, seven meteorological data points, and three active compounds were investigated in this study. We developed and validated an optimized method for quantifying active compounds using UPLC and performed correlation analysis of the environment, growth characteristics, and active compounds. The UPLC-UV method for determining active compounds was validated by measuring the linearity, LOD, LOQ, precision, and accuracy using UPLC. The LOD and LOQ were 0.01-0.03 µg/mL and 0.04-0.09 µg/mL, respectively. The precision was acceptable with RSD% values less than 2%. The recoveries ranged from 97.25 to 104.98% with RSD values <2%, within the acceptable limits. The active compounds were negatively correlated with the size of the fruit, and the growth characteristics were negatively correlated with some environmental factors. The results of this study can be used as basic data for the standard cultural practices and quality control of C. tricuspidata fruits.

8.
Sci Rep ; 13(1): 4781, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959274

RESUMO

Two-photon stereolithography (TPS) is widely used for the fabrication of various three-dimensional (3D) structures with sub-micron fabrication resolution in a single fabrication process. However, TPS is unsuitable for microstructures with fine-hole patterns. The laser ablation process can be easily drilled, or made holes in various materials. However, in the case of laser ablation, the focal plane of the laser is fixed, which is limited to the processing plane. In this study, a multidirectional ablation process is studied to apply laser ablation to various processing planes of a 3D microstructure fabricated by the TPS process. A 3D hybrid fabrication process with the advantages of both TPS and laser ablation is expected to improve the fabrication efficiency. The 3D hybrid process is proposed based on a single laser source. The microstructure is fabricated using TPS, and the multi-directional ablation process creates a hole in the lateral side of the 3D microstructure. To develop the multidirectional ablation process, the reflecting mirror system should be designed to adaptably rotate the laser focal plane and guide the laser path for the target process plane. Through various examples, we demonstrate the ability of the multi-directional ablation process with various examples.

9.
Materials (Basel) ; 16(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36984184

RESUMO

In this study, aluminum (Al) chip matrix-based synthetic foams were fabricated by hot pressing at a semi-solid (SS) temperature. The densities of the foams ranged from 2.3 to 2.63 g/cm3, confirming that the density decreased with increasing glass hollow sphere (GHS) content. These values were approximately 16% lower than the densities of Al chip alloys without GHS. The Al chip syntactic foam microstructure fabricated by the semi-solid process comprised GHS uniformly distributed around the Al chip matrix and a spherical microstructure surrounded by the Mg2Si phase in the interior. The resulting spherical microstructure contributed significantly to the improvement of mechanical properties. Mechanical characterization confirmed that the Al chip syntactic foam exhibited a compressive strength of approximately 225-288 MPa and an energy absorption capacity of 46-47 MJ/M3. These results indicate higher compressive properties than typical Al syntactic foam. The Al chip microstructure, consisting of the Mg2Si phase and GHS, acted as a load-bearing element during compression, significantly contributing to the compressive properties of the foam. An analysis was performed using an energy-dispersive spectrometer to validate the interfacial reaction between the GHS and the matrix. The results showed that MgAl2O4 was uniformly coated around GHS, which contributed not only to the strength of the matrix, but also to the mechanical properties via the appropriate interfacial reactive coating.

10.
J Mol Model ; 28(6): 168, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35612680

RESUMO

Dismutation reaction of superoxide radical catalyzed by EUK-134 has lower activation energy than non-catalytic reaction, and therefore, EUK-134 catalyzes dismutation reaction of superoxide radical. For non-catalytic dismutation reaction of hydrogen peroxide, there are three possible reaction paths, among which MEP3 has the lowest activation energy, and therefore, is thought to be the most probable reaction path. Dismutation reaction of hydrogen peroxide catalyzed by EUK-134 occurs in two successive steps and has lower energy barrier than non-catalytic dismutation reaction, and therefore, EUK-134 is thought to catalyze the dismutation reaction of hydrogen peroxide. HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) and ESP-fitted charge analysis of EUK-134 indicate that Mn atom plays an electron acceptor and donor for dismutation reactions of superoxide radical and hydrogen peroxide catalyzed by EUK-134, respectively.


Assuntos
Compostos Organometálicos , Superóxidos , Antioxidantes , Catalase , Peróxido de Hidrogênio , Salicilatos , Superóxido Dismutase
11.
Mol Ther ; 30(8): 2800-2816, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35526096

RESUMO

Several preclinical studies demonstrate that antitumor efficacy of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade can be improved by combination with other checkpoint inhibitors. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory checkpoint receptor involved in T cell exhaustion and tumor immune escape. Here, we describe ABL501, a bispecific antibody targeting LAG-3 and PD-L1 in modulating immune cell responses against tumors. ABL501 that efficiently inhibits both LAG-3 and PD-L1 pathways enhances the activation of effector CD4+ and CD8+ T cells with a higher degree than a combination of single anti-LAG-3 and anti-PD-L1. The augmented effector T cell responses by ABL501 resulted in mitigating regulatory-T-cell-mediated immunosuppression. Mechanistically, the simultaneous binding of ABL501 to LAG-3 and PD-L1 promotes dendritic cell (DC) activation and tumor cell conjugation with T cells that subsequently mounts effective CD8+ T cell responses. ABL501 demonstrates its potent in vivo antitumor efficacy in a humanized xenograft model and with knockin mice expressing human orthologs. The immune profiling analysis of peripheral blood reveals an increased abundance of LAG-3hiPD-1hi memory CD4+ T cell subset in relapsed cholangiocarcinoma patients after gemcitabine plus cisplatin therapy, which are more responsive to ABL501. This study supports the clinical evaluation of ABL501 as a novel cancer immunotherapeutic, and a first-in-human trial has started (NCT05101109).


Assuntos
Anticorpos Biespecíficos , Antígenos CD , Antígeno B7-H1 , Neoplasias , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Células Dendríticas , Camundongos , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Evasão Tumoral , Proteína do Gene 3 de Ativação de Linfócitos
12.
Sensors (Basel) ; 21(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884015

RESUMO

We propose a novel dual-channel electromyography (EMG) spatio-temporal differential (DESTD) method that can estimate volitional electromyography (vEMG) signals during time-varying functional electrical stimulation (FES). The proposed method uses two pairs of EMG signals from the same stimulated muscle to calculate the spatio-temporal difference between the signals. We performed an experimental study with five healthy participants to evaluate the vEMG signal estimation performance of the DESTD method and compare it with that of the conventional comb filter and Gram-Schmidt methods. The normalized root mean square error (NRMSE) values between the semi-simulated raw vEMG signal and vEMG signals which were estimated using the DESTD method and conventional methods, and the two-tailed t-test and analysis of variance were conducted. The results showed that under the stimulation of the gastrocnemius muscle with rapid and dynamically modulated stimulation intensity, the DESTD method had a lower NRMSE compared to the conventional methods (p < 0.01) for all stimulation intensities (maximum 5, 10, 15, and 20 mA). We demonstrated that the DESTD method could be applied to wearable EMG-controlled FES systems because it estimated vEMG signals more effectively compared to the conventional methods under dynamic FES conditions and removed unnecessary FES-induced EMG signals.


Assuntos
Músculo Esquelético , Estimulação Elétrica , Eletromiografia , Humanos
13.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34230109

RESUMO

BACKGROUND: Stimulation of 4-1BB with agonistic antibodies is a promising strategy for improving the therapeutic efficacy of immune checkpoint inhibitors (ICIs) or for overcoming resistance to ICIs. However, dose-dependent hepatotoxicity was observed in clinical trials with monoclonal anti-4-1BB agonistic antibodies due to the activation of 4-1BB signaling in liver resident Kupffer cells. METHODS: To avoid this on-target liver toxicity, we developed a novel bispecific antibody (4-1BB×PD-L1 bispecific antibody, termed "ABL503") uniquely designed to activate 4-1BB signaling only in the context of PD-L1, while also blocking PD-1/PD-L1 signaling. RESULTS: Functional evaluation using effector cells expressing both 4-1BB and PD-1 revealed superior biological activity of ABL503 compared with the combination of each monoclonal antibody. ABL503 also augmented T-cell activation in in vitro assays and further enhanced the anti-PD-L1-mediated reinvigoration of tumor-infiltrating CD8+ T cells from patients with cancer. Furthermore, in humanized PD-L1/4-1BB transgenic mice challenged with huPD-L1-expressing tumor cells, ABL503 induced superior anti-tumor activity and maintained an anti-tumor response against tumor rechallenge. ABL503 was well tolerated, with normal liver function in monkeys. CONCLUSION: The novel anti-4-1BB×PD-L1 bispecific antibody may exert a strong anti-tumor therapeutic efficacy with a low risk of liver toxicity through the restriction of 4-1BB stimulation in tumors.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Animais , Anticorpos Biespecíficos/farmacologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Camundongos
14.
Respir Res ; 22(1): 189, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183009

RESUMO

BACKGROUND: In this study, we tested whether a combination of radiomic features extracted from baseline pre-immunotherapy computed tomography (CT) images and clinicopathological characteristics could be used as novel noninvasive biomarkers for predicting the clinical benefits of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: The data from 92 consecutive patients with lung cancer who had been treated with ICIs were retrospectively analyzed. In total, 88 radiomic features were selected from the pretreatment CT images for the construction of a random forest model. Radiomics model 1 was constructed based on the Rad-score. Using multivariate logistic regression analysis, the Rad-score and significant predictors were integrated into a single predictive model (radiomics nomogram model 1) to predict the durable clinical benefit (DCB) of ICIs. Radiomics model 2 was developed based on the same Rad-score as radiomics model 1.Using multivariate Cox proportional hazards regression analysis, the Rad-score, and independent risk factors, radiomics nomogram model 2 was constructed to predict the progression-free survival (PFS). RESULTS: The models successfully predicted the patients who would benefit from ICIs. For radiomics model 1, the area under the receiver operating characteristic curve values for the training and validation cohorts were 0.848 and 0.795, respectively, whereas for radiomics nomogram model 1, the values were 0.902 and 0.877, respectively. For the PFS prediction, the Harrell's concordance indexes for the training and validation cohorts were 0.717 and 0.760, respectively, using radiomics model 2, whereas they were 0.749 and 0.791, respectively, using radiomics nomogram model 2. CONCLUSIONS: CT-based radiomic features and clinicopathological factors can be used prior to the initiation of immunotherapy for identifying NSCLC patients who are the most likely to benefit from the therapy. This could guide the individualized treatment strategy for advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Processamento de Imagem Assistida por Computador/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
15.
MAbs ; 13(1): 1914885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33904380

RESUMO

Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and narrow therapeutic windows. To overcome these limitations, we have applied reductive alkylation to develop a new type of ADC that has cytotoxic drugs conjugated to the N-terminal of an antibody through amine bonds introduced via reductive alkylation reactions (NTERM). To test whether the NTERM-conjugated ADCs can widen therapeutic windows, we synthesized three different ADCs by conjugating trastuzumab and monomethyl auristatin-F using three different methods, and compared their stability, efficacy, and toxicity. The NTERM-conjugated ADC was more stable in vitro and in vivo than the thiol-conjugated and the lysine-conjugated ADCs. The NTERM-conjugated ADC showed lower toxicity compared to other ADCs, whereas its efficacy was comparable to that of the thiol-conjugated ADC and better than that of the lysine-conjugated ADC. These results suggest that the NTERM conjugation method could widen the therapeutic window of ADCs by enhancing its stability and reducing toxicity.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Imunoconjugados/farmacologia , Oligopeptídeos/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/farmacologia , Alquilação , Animais , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/toxicidade , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Composição de Medicamentos , Estabilidade de Medicamentos , Feminino , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoconjugados/toxicidade , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Estabilidade Proteica , Ratos Nus , Ratos Sprague-Dawley , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Trastuzumab/química , Trastuzumab/farmacocinética , Trastuzumab/toxicidade , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Sci Adv ; 7(3)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523913

RESUMO

Cancer immunotherapy with 4-1BB agonists has limited further clinical development because of dose-limiting toxicity. Here, we developed a bispecific antibody (bsAb; B7-H3×4-1BB), targeting human B7-H3 (hB7-H3) and mouse or human 4-1BB, to restrict the 4-1BB stimulation in tumors. B7-H3×m4-1BB elicited a 4-1BB-dependent antitumor response in hB7-H3-overexpressing tumor models without systemic toxicity. BsAb primarily targets CD8 T cells in the tumor and increases their proliferation and cytokine production. Among the CD8 T cell population in the tumor, 4-1BB is solely expressed on PD-1+Tim-3+ "terminally differentiated" subset, and bsAb potentiates these cells for eliminating the tumor. Furthermore, the combination of bsAb and PD-1 blockade synergistically inhibits tumor growth accompanied by further increasing terminally differentiated CD8 T cells. B7-H3×h4-1BB also shows antitumor activity in h4-1BB-expressing mice. Our data suggest that B7-H3×4-1BB is an effective and safe therapeutic agent against B7-H3-positive cancers as monotherapy and combination therapy with PD-1 blockade.


Assuntos
Anticorpos Biespecíficos , Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral , Neoplasias , Animais , Anticorpos Biespecíficos/farmacologia , Linfócitos T CD8-Positivos/imunologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1
17.
Korean J Anesthesiol ; 74(1): 38-44, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32013327

RESUMO

BACKGROUND: Shoulder surgery in the beach chair position frequently causes hypotensive bradycardic events (HBEs), which are potentially associated with an increased risk of cerebral hypoperfusion. Here, we aimed to investigate the incidence and characteristics of symptomatic HBEs that require pharmacological interventions, and to identify specific risk factors associated with symptomatic HBEs. METHODS: We retrospectively examined the records of all patients aged ≥ 18 years who underwent shoulder arthrotomy in the beach chair position between January 2011 and December 2018 at Samsung Medical Center. For patients who experienced HBEs while in the beach chair position, the minimum heart rate and systolic blood pressure were noted, as was the total dose of ephedrine or atropine. RESULTS: Symptomatic HBEs occurred in 61.0% of all cases (256/420). Two patients with symptomatic HBEs experienced postoperative neurological complications. Multivariable logistic regression analysis showed that preoperative interscalene brachial plexus block (ISB) and advanced age were risk factors associated with symptomatic HBEs (odds ratio [OR]: 3.240, 95% CI: 2.003, 5.242, P < 0.001; OR: 1.060 for each 1-year increase, 95% CI: 1.044, 1.076, P < 0.001, respectively). Receiver operating curve analysis revealed that a threshold of 62 years of age had a moderate degree of accuracy for predicting symptomatic HBEs (area under curve: 0.764, 95% CI: 0.720, 0.804, P < 0.001). CONCLUSIONS: Considering the increasing risk of neurocognitive complications with aging, proactive hemodynamic management is needed, especially for elderly patients undergoing shoulder surgery in the beach chair position using ISB.


Assuntos
Bradicardia , Ombro , Idoso , Humanos , Posicionamento do Paciente , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Ombro/cirurgia
18.
J Atten Disord ; 25(8): 1080-1095, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-31640464

RESUMO

Objective: We aimed to understand whether Attention Deficit Hyperactivity Disorder (ADHD) and Internet gaming disorder (IGD) share similar brain functional connectivity (FC) between the frontal and subcortices. Method: We compared changes in clinical symptoms and brain activity using functional magnetic resonance imaging (fMRI) in 26 patients with ADHD but without IGD, 29 patients with ADHD and IGD, and 20 patients with IGD but without ADHD. Results: The functional connectivity (FC) from the cortex to subcortex in both groups was decreased relative to that in age-matched healthy participants. One-year treatment for ADHD and IGD symptoms increased the FC between the cortex and subcortex in all ADHD participants and all IGD participants with good prognoses compared with those in all ADHD participants and all IGD participants with poor prognoses. Conclusion: Patients with ADHD and IGD shared similar brain FC at baseline and FC changes in response to treatment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Aditivo , Jogos de Vídeo , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Comportamento Aditivo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Internet , Transtorno de Adição à Internet , Imageamento por Ressonância Magnética
19.
3D Print Addit Manuf ; 8(5): 293-301, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36654934

RESUMO

Biomass materials, an important source of chemical feedstocks, could replace fossil fuels as a resource in the future. The chemical feedstocks from biomass materials are used in many medical and pharmaceutical products and in fuels, chemicals, and functional materials. Biomass materials are expected to be used in biomedical engineering fields, especially due to their low biotoxicity. By the way, most of the demand for bio-application fields is an application targeted for customized production, so a high formability is required for production. Research on three-dimensional (3D) printing technology capable of satisfying these requirements has been ongoing. Manufacturing additives need to be investigated to use biomass materials as a resin or bioink safely for 3D printing, which is a technique widely used in biomedical engineering fields. In this study, a projection microstereolithography (PµSL) system, a 3D printing technique, was made that uses a biomass-based resin. Biomass materials are designed to be photocurable for use in the PµSL process. Various PµSL process parameters were investigated using the biomass-based resin to determine the optimum fabrication conditions for 3D structures. This study demonstrated that a biomass-based resin can be used in the PµSL process. We provide a method for its application in various biomedical engineering fields.

20.
Mater Sci Eng C Mater Biol Appl ; 118: 111406, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33255009

RESUMO

An artificial blood vessel with a tubular structure was additively manufactured via fused deposition modeling (FDM) starting from a single strand of polyvinyl alcohol (PVA) filament coated with a specific thickness of biocompatible polydimethylsiloxane (PDMS), followed by removal of the inner core via hydrogen peroxide leaching under sonication. In particular, we examined the relationship between the extruded deposition diameter and the filament migration speed/nozzle control speed (referred to as the filament/nozzle transition ratio), which is almost independent of the extruded deposition flow rate due to the weak die-swelling and memory effects of the extruded PVA arising from its intrinsically low viscoelasticity. The chemical stability of the PDMS during sonication in the hydrogen peroxide solution was then determined by spectroscopic techniques. The PDMS displayed no mechanical degradation in the hydrogen peroxide solution, resulting in similar fracture elongation and yield strength to those of the pristine specimen without the leaching treatment. As a further advantage, the inside surface of the PDMS was smooth regardless of the hydrogen peroxide leaching under sonication. The potential application of the as-developed scaffold in soft tissue engineering (particularly that involving vascular tissue regeneration) was demonstrated by the successful transplantation of the artificial blood vessel in a right-hand surgical replica used in a clinical simulation.


Assuntos
Substitutos Sanguíneos , Álcool de Polivinil , Engenharia Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...