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Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.
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Receptores de Hialuronatos , Ácido Hialurônico , Imunoterapia , Células Matadoras Naturais , Células Matadoras Naturais/imunologia , Receptores de Hialuronatos/metabolismo , Animais , Humanos , Imunoterapia/métodos , Ácido Hialurônico/química , Linhagem Celular Tumoral , Ligantes , Camundongos , Polietilenoglicóis/química , Neoplasias/terapia , Neoplasias/imunologiaRESUMO
The potential for various future industrial applications has made broadband photodetectors beyond visible light an area of great interest. Although most 2D van-der-Waals (vdW) semiconductors have a relatively large energy bandgap (>1.2 eV), which limits their use in short-wave infrared detection, they have recently been considered as a replacement for ternary alloys in high-performance photodetectors due to their strong light-matter interaction. In this study, a ferroelectric gating ReS2 /WSe2 vdW heterojunction-channel photodetector is presented that successfully achieves broadband light detection (>1300 nm, expandable up to 2700 nm). The staggered type-II bandgap alignment creates an interlayer gap of 0.46 eV between the valence band maximum (VBMAX ) of WSe2 and the conduction band minimum (CBMIN ) of ReS2 . Especially, the control of poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric dipole polarity for a specific wavelength allows a high photoresponsivity of up to 6.9 × 103 A W-1 and a low dark current below 0.26 nA under the laser illumination with a wavelength of 405 nm in P-up mode. The achieved high photoresponsivity, low dark current, and full-range near infrared (NIR) detection capability open the door for next-generation photodetectors beyond traditional ternary alloy photodetectors.
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Phenylboronic acid (PBA) has been highly acknowledged as a significant cancer recognition moiety in sialic acid-overexpressing cancer cells. In this investigation, lipid-mediated biomaterial integrated PBA molecules onto the surface of natural killer (NK) cells to make a receptor-mediated immune cell therapeutic module. Therefore, a 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-conjugated di-PEG-PBA (DSPEPEG-di(PEG-PBA) biomaterial was synthesized. The DSPEPEG-di(PEG-PBA) biomaterial exhibited a high affinity for sialic acid (SA), confirmed by fluorescence spectroscopy at pH 6.5 and 7.4. DSPEPEG-di(PEG-PBA) was successfully anchored onto NK cell surfaces (PBA-NK), and this biomaterial maintains intrinsic properties such as viability, ligand availability (FasL & TRAIL), and cytokine secretion response to LPS. The anticancer efficacy of PBA-NK cells was evaluated against 2D cancer cells (MDA-MB-231, HepG2, and HCT-116) and 3D tumor spheroids of MDA-MB-231 cells. PBA-NK cells exhibited greatly enhanced anticancer effects against SA-overexpressing cancer cells. Thus, PBA-NK cells represent a new anticancer strategy for cancer immunotherapy.
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Ácido N-Acetilneuramínico , Neoplasias , Humanos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/uso terapêutico , Neoplasias/tratamento farmacológico , Células Matadoras Naturais , Lipídeos , Materiais Biocompatíveis/uso terapêuticoRESUMO
Triple-negative breast cancer (TNBC) presents treatment challenges due to a lack of detectable surface receptors. Natural killer (NK) cell-based adaptive immunotherapy is a promising treatment because of the characteristic anticancer effects of killing malignant cells directly by secreting cytokines and lytic granules. To maximize the cancer recognition ability of NK cells, biomaterial-mediated ex vivo cell surface engineering has been developed for sufficient cell membrane immobilization of tumor-targeting ligands via hydrophobic anchoring. In this study, we optimized amphiphilic balances of NK cell coating materials composed of CD44-targeting hyaluronic acid (HA)-poly(ethylene glycol) (PEG)-lipid to improve TNBC recognition and the anticancer effect. Changes in the modular design of our material by differentiating hydrophilic PEG length and incorporating lipid amount into HA backbones precisely regulated the amphiphilic nature of HA-PEG-lipid conjugates. The optimized biomaterial demonstrated improved anchoring into NK cell membranes and facilitating the surface presentation level of HA onto NK cell surfaces. This led to enhanced cancer targeting via increasing the formation of immune synapse, thereby augmenting the anticancer capability of NK cells specifically toward CD44-positive TNBC cells. Our approach addresses targeting ability of NK cell to solid tumors with a deficiency of surface tumor-specific antigens while offering a valuable material design strategy using amphiphilic balance in immune cell surface engineering techniques.
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Ácido Hialurônico , Neoplasias de Mama Triplo Negativas , Humanos , Ácido Hialurônico/química , Linhagem Celular Tumoral , Materiais Biocompatíveis/farmacologia , Células Matadoras Naturais , Lipídeos , Receptores de Hialuronatos/metabolismoRESUMO
Haloarchaea produce bacterioruberin, a major C50 carotenoid with antioxidant properties that allow for its potential application in the food, cosmetic, and pharmaceutical industries. This study aimed to optimize culture conditions for total carotenoid, predominantly comprising bacterioruberin, production using Halorubrum ruber MBLA0099. A one-factor-at-a-time and statistically-based experimental design were applied to optimize the culture conditions. Culture in the optimized medium caused an increase in total carotenoid production from 0.496 to 1.966 mg L- 1 Maximal carotenoid productivity was achieved in a 7-L laboratory-scale fermentation and represented a 6.05-fold increase (0.492 mg L-1 d-1). The carotenoid extracts from strain MBLA0099 exhibited a 1.8-10.3-fold higher antioxidant activity in vitro, and allowed for a higher survival rate of Caenorhabditis elegans under oxidative stress conditions. These results demonstrated that Hrr. ruber MBLA0099 has significant potential as a haloarchaon for the commercial production of bacterioruberin.
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Antioxidantes , Halorubrum , CarotenoidesRESUMO
Conductive-bridge random access memory can be used as a physical reservoir for temporal learning in reservoir computing owing to its volatile nature. Herein, a scaled Cu/HfOx/n+-Si memristor was fabricated and characterized for reservoir computing. The scaled, silicon nanofin bottom electrode formation is verified by scanning electron and transmission electron microscopy. The scaled device shows better cycle-to-cycle switching variability characteristics compared with those of large-sized cells. In addition, synaptic characteristics such as conductance changes due to pulses, paired-pulse facilitation, and excitatory postsynaptic currents are confirmed in the scaled memristor. High-pattern accuracy is demonstrated by deep neural networks applied in neuromorphic systems in conjunction with the use of the Modified National Institute of Standards and Technology database. Furthermore, a reservoir computing system is introduced with six different states attained by adjusting the amplitude of the input pulse. Finally, high-performance and efficient volatile reservoir computing in the scaled device is demonstrated by conductance control and system-level reservoir computing simulations.
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Here, we demonstrate double-layer 3D vertical resistive random-access memory with a hole-type structure embedding Pt/HfOx/AlN/TiN memory cells, conduct analog resistive switching, and examine the potential of memristors for use in neuromorphic systems. The electrical characteristics, including resistive switching, retention, and endurance, of each layer are also obtained. Additionally, we investigate various synaptic characteristics, such as spike-timing dependent plasticity, spike-amplitude dependent plasticity, spike-rate dependent plasticity, spike-duration dependent plasticity, and spike-number dependent plasticity. This synapse emulation holds great potential for neuromorphic computing applications. Furthermore, potentiation and depression are manifested through identical pulses based on DC resistive switching. The pattern recognition rates within the neural network are evaluated, and based on the conductance changing linearly with incremental pulses, we achieve a pattern recognition accuracy of over 95%. Finally, the device's stability and synapse characteristics exhibit excellent potential for use in neuromorphic systems.
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Eletricidade , Redes Neurais de ComputaçãoRESUMO
This study systematically investigates analog switching and neuromorphic characteristics in a ZnO-based memristor by varying the anodic top electrode (TE) materials [indium tin oxide (ITO), Ti, and Ta]. Compared with the TE materials (Ti and Ta), memristive devices with TEs made of ITO exhibit dual volatile and nonvolatile switching behavior and multistate switching characteristics assessed based on reset-stop voltage and current compliance (ICC) responses. The polycrystalline structure of the ZnO functional layer sandwiched between ITO electrodes was confirmed by high-resolution transmission electron microscopy analysis. The current transport mechanism in the ZnO-based memristor was dominated by Schottky emission, with the Schottky barrier height modulated from 0.26 to 0.4 V by varying the reset-stop voltage under different ICC conditions. The long-term potentiation and long-term depression synaptic characteristics were successfully mimicked by modulating the pulse amplitudes. Furthermore, a 90.84% accuracy was achieved using a convolutional neural network architecture for Modified National Institute of Standards and Technology pattern categorization, as demonstrated by the confusion matrix. The results demonstrated that the ITO/ZnO/ITO/Si memristor device holds promise for high-performance electronic applications and effective ITO electrode modeling.
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Efficient data processing is heavily reliant on prioritizing specific stimuli and categorizing incoming information. Within human biological systems, dorsal root ganglions (particularly nociceptors situated in the skin) perform a pivotal role in detecting external stimuli. These neurons send warnings to our brain, priming it to anticipate potential harm and prevent injury. In this study, we explore the potential of using a ferroelectric memristor device structured as a metal-ferroelectric-insulator-semiconductor as an artificial nociceptor. The aim of this device is to electrically receive external damage and interpret signals of danger. The TiN/HfAlOx (HAO)/HfSiOx (HSO)/n+ Si configuration of this device replicates the key functions of a biological nociceptor. The emulation includes crucial aspects, such as threshold reactivity, relaxation, no adaptation, and sensitization phenomena known as "allodynia" and "hyperalgesia." Moreover, we propose establishing a connection between nociceptors and synapses by training the Hebbian learning rule. This involves exposing the device to injurious stimuli and using this experience to enhance its responsiveness, replicating synaptic plasticity.
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Nociceptores , Sinapses , Sinapses/fisiologia , Nociceptores/fisiologia , Humanos , Háfnio/química , SemicondutoresRESUMO
This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology.
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PURPOSE: To analyse whether valgus laxity and clinical outcomes differ depending on whether the superficial medial collateral ligament (sMCL) is released or transected during medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Consecutive patients who underwent MOWHTO and subsequent radiological follow-up for at least 2 years were retrospectively evaluated. The patients were divided into release and transection groups, according to the sMCL manipulation technique. Each patient was assessed for the following variables on valgus stress radiographs taken before surgery and at the 12- and 24-month follow-ups: the absolute value of valgus (ABV) and side-to-side difference (SSD) between the affected and normal sides. The differences between preoperative SSD and those at 12 and 24 months were respectively calculated and defined as delta SSD (ΔSSD). The Visual Analogue Scale, Lysholm knee, International Knee Documentation Committee subjective, and Knee Injury and Osteoarthritis Outcome scores were used to evaluate patient-reported outcomes. RESULTS: Eighty-five patients were included in the study. Forty-two patients (49.6%) underwent sMCL release, and the remaining 43 patients (50.4%) underwent sMCL transection. No significant differences were observed in the ABV and SSD of valgus laxity at the different time points between the two groups (n.s.). Furthermore, no significant differences were observed in the ΔSSD at the 12- and 24-month follow-ups between the two groups (n.s.). Significant improvement from preoperative values was observed in all patient-reported outcomes (p < 0.001), with no significant differences between the two groups at any time point (n.s.). CONCLUSION: Significant improvements in clinical outcomes were observed, regardless of the technique used. Postoperative valgus laxity did not occur with either technique. The transection technique, which can be performed more simply and quickly, demonstrated similar clinical outcomes and valgus laxity to the release technique. LEVEL OF EVIDENCE: Level III.
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Ligamentos Colaterais , Instabilidade Articular , Osteoartrite do Joelho , Humanos , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Osteoartrite do Joelho/cirurgiaRESUMO
PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.
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Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Osteoartrite do Joelho , Humanos , Cartilagem Hialina , Cartilagem Articular/cirurgia , Estudos de Coortes , Estudos Prospectivos , Hialina , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Resultado do Tratamento , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
PURPOSE: The aim of this study was to analyse the factors associated with additional postoperative alignment changes after accurate bony correction by selecting only patients with well-performed bony correction as planned and develop a method of incorporating significant factors into preoperative planning. METHODS: Among 104 consecutive patients who underwent medial open wedge high tibial osteotomy (MOWHTO) between October 2019 and July 2022, 61 with well-performed bony corrections were retrospectively reviewed. The major criterion for well-performed bony correction was a difference of <1° between the simulated medial proximal tibial angle (MPTA) and the actual postoperative MPTA as measured in three dimensions. Radiographic parameters, such as the joint line convergence angle (JLCA) and joint line obliquity (JLO), were measured preoperatively and postoperatively, utilising standing and supine whole lower extremity anteroposterior, valgus and varus stress radiographs. Multiple linear regression analysis identified the factors affecting alignment changes, and a prediction model was developed. A method for applying this prediction model to preoperative planning was proposed. RESULTS: Preoperative JLCA on standing (preJLCAstd ), preoperative JLCA on 0° valgus stress radiograph (vgJLCA0 ), and preoperative JLO (preJLO) were significantly correlated with JLCA change (∆JLCA) (p < 0.001, p < 0.001, p = 0.006). The prediction model was estimated as ∆JLCA = 0.493 × (vgJLCA0 ) - 0.727 × (preJLCAstd ) + 0.189 × (preJLO) - 1.587 in. (R = 0.815, modified R2 = 0.646, p < 0.001). The proposed method resulted in a reduced overcorrection rate (p = 0.003) and an improved proportion of acceptable alignments (p = 0.013). CONCLUSION: PreJLCAstd , vgJLCA0 and preJLO can be used to estimate ∆JLCA. PreJLO was recently identified as a significant factor associated with additional alignment changes. Utilising the proposed preoperative planning and a prediction model with these factors shows promise in calibrating postoperative alignment after MOWHTO. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
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Articulação do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Osteotomia/métodosRESUMO
Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Fígado/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismoRESUMO
Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.
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Citocinas , Células Matadoras Naturais , Células Matadoras Naturais/metabolismo , Citocinas/metabolismo , Transdução de Sinais , Interferon gama/metabolismo , LipídeosRESUMO
INTRODUCTION: To seek an optimal measurement method with high reliability and high validity for evaluation of the anterior knee laxity on stress radiographs and comparing the translation values to those of KT-2000 arthrometer. METHODS: Anterior knee laxity in 77 patients was measured preoperatively using the TelosTM and the KT-2000 arthrometer. Side-to-side difference measurements were taken using three conventional measuring methods and one proposed method (Modified Lateral). The knee position on the stress radiograph was evaluated and scored based on the stress radiograph qualifying criteria depending on stress film correctiveness. Intraclass correlation coefficients were analyzed to evaluate the reliability of the measurement methods and were compared between high (Group H) and low (Group L) radiograph quality score groups for each method. Validity was assessed by comparing the KT-2000 and the TelosTM using Pearson correlation (r value). RESULTS: The Modified Lateral method showed the best Intraclass Correlation Coefficients (ICCs), followed by Center to Center, and Medial to Medial and Lateral to Lateral methods without considering the quality of Telos. In the comparison between groups based on Telos quality for intra-rater reliability, the Medial to Medial (MM) method demonstrated the best reliability in both groups (MM: ICCs, Group H = 0.942, Group L = 0.917, P = 0.693). As for inter-rater reliability, the Modified Lateral (ML) method exhibited the best reliability in both groups (ML: ICCs, Group H = 0.923, Group L = 0.882, P = 0.547). The value measured using the ML method in Telos showed the highest correlation coefficient with the KT-2000 measured value in both groups H and L. There were no statistically significant differences among the correlation coefficient values. CONCLUSION: The Modified Lateral method is recommended for its high reliability, taking into account the differences in bilateral knee positions and anatomical discriminability on stress radiographs when evaluating anterior knee translation with Telos. It also best reflected the KT-2000 arthrometer. LEVEL OF EVIDENCE: Case Series, Level IV.
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Lesões do Ligamento Cruzado Anterior , Instabilidade Articular , Humanos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/diagnóstico , Reprodutibilidade dos Testes , Feminino , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Adulto , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Articulação do Joelho/diagnóstico por imagem , Artrometria Articular/métodos , Adolescente , Radiografia/métodosRESUMO
Natural killer (NK) cells exhibit a good therapeutic efficacy against various malignant cancer cells. However, the therapeutic efficacy of plain NK cells is relatively low due to inadequate selectivity for cancer cells. Therefore, to enhance the targeting selectivity and anticancer efficacy of NK cells, we have rationally designed a biomaterial-mediated ex vivo surface engineering technique for the membrane decoration of cancer recognition ligands onto NK cells. Our designed lipid conjugate biomaterial contains three major functional moieties: (1) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid for cell membrane anchoring, (2) polyethylene glycol for intracellular penetration blocker, and (3) lactobionic acid (LBA) for cancer recognition. The biomaterial was successfully applied to NK cell surfaces (LBA-NK) to enhance recognition and anticancer functionalities, especially toward asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma. Highly efficient and homogeneous NK cell surface editing was achieved with a simple coating process while maintaining intrinsic properties of NK cells. LBA-NK cells showed potential ASGPR-mediated tumor cell binding (through LBA-ASGPR interaction) and thereby significantly augmented anticancer efficacies against HepG2 liver cancer cells. Thus, LBA-NK cells can be a novel engineering strategy for the treatment of liver cancers via facilitated immune synapse interactions in comparison with currently available cell therapies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Materiais Biocompatíveis/metabolismo , Células Matadoras Naturais , Lipídeos/uso terapêuticoRESUMO
Intersubband polar-optical-phonon (POP) scattering plays an important role in determining the population inversion and optical gain of mid-infrared (mid-IR) quantum cascade lasers (QCLs). In particular, the nonparabolicity of the conduction band (CB) significantly affects the energy dispersion relation and intersubband POP scattering time. However, the currently used parabolic-band (PB) and nonparabolic-band (NPB) energy dispersion models are not appropriate for mid-IR QCLs because they are unsuitable for high electron wave vectors and do not consider the effect of applied strain on the energy dispersion relation of the CB. The eight-band k·p method can provide a relatively accurate nonparabolic energy dispersion relation for high electron wave vectors but has the disadvantages of high computational complexity and spurious solutions to be discarded. Consequently, we propose a strain-modified improved nonparabolic-band (INPB) energy dispersion model that has no spurious solution and acceptable accuracy, compared to the eight-band k·p method. To demonstrate the accuracy and efficiency of our proposed INPB model compared with those of the PB, NPB, and eight-band k·p models, we calculate the energy dispersion relations and intersubband POP scattering times in a strain-compensated QCL with a lasing wavelength of 3.58â µm. Calculation results reveal that our proposed model is almost as accurate as the eight-band k·p model; however, it enables much faster calculations and is free from spurious solutions.
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A substantial amount of research effort has been directed toward the development of Pt-based catalysts with higher performance and durability than conventional polycrystalline Pt nanoparticles to achieve high-power and innovative energy conversion systems. Currently, attention has been paid toward expanding the electrochemically active surface area (ECSA) of catalysts and increase their intrinsic activity in the oxygen reduction reaction (ORR). However, despite innumerable efforts having been carried out to explore this possibility, most of these achievements have focused on the rotating disk electrode (RDE) in half-cells, and relatively few results have been adaptable to membrane electrode assemblies (MEAs) in full-cells, which is the actual operating condition of fuel cells. Thus, it is uncertain whether these advanced catalysts can be used as a substitute in practical fuel cell applications, and an improvement in the catalytic performance in real-life fuel cells is still necessary. Therefore, from a more practical and industrial point of view, the goal of this review is to compare the ORR catalyst performance and durability in half- and full-cells, providing a differentiated approach to the durability concerns in half- and full-cells, and share new perspectives for strategic designs used to induce additional performance in full-cell devices.
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Platina , Polímeros , Catálise , Eletrodos , Eletrólitos/química , Platina/química , Polímeros/químicaRESUMO
The ferroelectric characteristics of a metal-ferroelectric-metal (MFM) ferroelectric tunneling junction (FTJ) capacitor device are investigated herein. The device consists of an aluminum-doped hafnium oxide (HAO) insulator sandwiched between tungsten (W) and titanium nitride (TiN) metal electrodes. Rapid thermal annealing (RTA) is performed for 20 s under a nitrogen atmosphere at temperatures of 750 °C, 800 °C, and 850 °C to find that ferroelectricity with a large remanent polarization (Pr) of 41.28 µC cm-2 can be obtained at the optimum annealing temperature of 800 °C. The presence of ferroelectricity is confirmed by polarization-switching positive-up-negative-down (PUND) measurements and by the hysteric polarization-voltage (P-V) loop. All devices exhibit excellent reliability, with an endurance of up to â¼106 cycles and long retention characteristics. In addition, the interfacial paraelectric capacitance (Ci) values of the three HAO FTJs are investigated via pulse-switching measurements. The results indicate that the HAO film annealed at 800 °C for 20 s exhibits an excellent tunneling electro-resistance (TER) ratio of 186% and this is attributed to the extra paraelectric layer formed between the ferroelectric layer and the bottom electrode. The detailed findings of this study are expected to assist in the development of hafnium oxide-based ferroelectric non-volatile memory applications.