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HfO2-based ferroelectric materials as the most promising candidate for the ferroelectric memories, have been widely studied for more than a decade due to their excellent ferroelectric properties and CMOS compatibility. In order to realize its industrialization as soon as possible, researchers have been devoted to improving the reliability performance, such as wake up, imprint, limited endurance, et al. Among them, the breakdown characteristic is one of main failure mechanisms of HfO2-based ferroelectric devices, which limits the write/read reliability of the devices. Based on this, we systematically studied the effect of thickness on the time-dependent dielectric breakdown (TDDB) tolerate capability of HfO2-ZrO2(HZO) FE films under both forward and reverse electrical stress conditions. The thickness of HZO FE film ranged from 6 to 20 nm. Our findings reveal that decreasing the thickness of the HZO FE film leads to an improvement in TDDB tolerance capability which is attributed to the fact that higher density of oxygen vacancies in thinner HZO FE films can effectively inhibit the generation of new oxygen vacancies and the growth of conductive filaments, thus effectively improving the TDDB characteristics. These results provide a potential solution for mitigating breakdown characteristics of HfO2-based ferroelectric devices in memory applications.
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Background: Reaction time is a reliable indicator of the velocity and efficiency of neuromuscular control and may be associated with fear-avoidance beliefs. However, the effect of exercise-induced muscle fatigue on reaction time in chronic low back pain (cLBP) and its relationship with fear-avoidance beliefs remains poorly understood. Objectives: This study aimed to reveal the relationship between fear-avoidance beliefs and reaction time changes before and after exercise-induced muscle fatigue in cLBP. Methods: Twenty-five patients with cLBP were tested by the Biering-Sorensen test (BST) to induce exhaustive muscle fatigue. Total reaction time (TRT), premotor time (PMT), and electromechanical delay (EMD) of dominated deltoid muscle were recorded by surface electromyography during the arm-raising task with visual cues before and after muscle fatigue. The mean difference (MD) of TRT (MDTRT), PMT (MDPMT), and EMD (MDEMD) was calculated from the changes before and after muscle fatigue. Fear-avoidance beliefs questionnaire (FABQ) was applied to evaluate fear-avoidance beliefs before muscle fatigue. In addition, the duration time of BST was recorded for each subject. Results: TRT and PMT of dominated deltoid muscle were prolonged after exercise-induced muscle fatigue (Z = 3.511, p < 0.001; t = 3.431, p = 0.001), while there was no statistical difference in EMD (Z = 1.029, p = 0.304). Correlation analysis showed that both the MDTRT and MDPMT were positively correlated with FABQ (r = 0.418, p = 0.042; r = 0.422, p = 0.040). Conclusions: These findings suggested that we should pay attention to both muscle fatigue-induced reaction time delay in cLBP management and the possible psychological mechanism involved in it. Furthermore, this study implied that FABQ-based psychotherapy might serve as a potential approach for cLBP treatment by improving reaction time delay. This trial is registered with ChiCTR2300074348.
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Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Fatiga Muscular/fisiología , Tiempo de Reacción , Electromiografía , Miedo/psicología , Encuestas y Cuestionarios , Evaluación de la DiscapacidadRESUMEN
There is an unmet clinical need to develop novel strategies to overcome resistance to tyrosine kinase inhibitors (TKI) in patients with oncogene-driven lung adenocarcinoma (LUAD). The objective of this study was to determine whether simvastatin could overcome TKI resistance using the in vitro and in vivo LUAD models. Human LUAD cell lines, tumor cells, and patient-derived xenograft (PDX) models from TKI-resistant LUAD were treated with simvastatin, either alone or in combination with a matched TKI. Tumor growth inhibition was measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and expression of molecular targets was assessed by immunoblots. Tumors were assessed by histopathology, IHC stain, immunoblots, and RNA sequencing. We found that simvastatin had a potent antitumor effect in tested LUAD cell lines and PDX tumors, regardless of tumor genotypes. Simvastatin and TKI combination did not have antagonistic cytotoxicity in these LUAD models. In an osimertinib-resistant LUAD PDX model, simvastatin and osimertinib combination resulted in a greater reduction in tumor volume than simvastatin alone (P < 0.001). Immunoblots and IHC stain also confirmed that simvastatin inhibited TKI targets. In addition to inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, RNA sequencing and Western blots identified the proliferation, migration, and invasion-related genes (such as PI3K/Akt/mTOR, YAP/TAZ, focal adhesion, extracellular matrix receptor), proteasome-related genes, and integrin (α3ß1, αvß3) signaling pathways as the significantly downregulated targets in these PDX tumors treated with simvastatin and a TKI. The addition of simvastatin is a safe approach to overcome acquired resistance to TKIs in several oncogene-driven LUAD models, which deserve further investigation.
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Adenocarcinoma del Pulmón , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Simvastatina , Animales , Femenino , Humanos , Ratones , Adenocarcinoma del Pulmón/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Oncogenes , Simvastatina/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
HfO2-ZrO2 ferroelectric films have recently gained considerable attention from integrated circuit researchers due to their excellent ferroelectric properties over a wide doping range and low deposition temperature. In this work, different HfO2-ZrO2 superlattice (SL) FE films with varying periodicity of HfO2 (5 cycles)-ZrO2 (5 cycles) (SL5), HfO2 (10 cycles)-ZrO2 (10 cycles) (SL10), and HfO2 (15 cycles)-ZrO2 (15 cycles) (SL15) were studied systematically. The HfZrOx (HZO) alloy was used as a comparison device. The SL5 film demonstrated improved ferroelectric properties compared to the HZO film, with the 2 times remnant polarization (2Pr) values increasing from 41.4 to 48.6 µC/cm2 at an applied voltage of 3 V/10 kHz. Furthermore, the first-order reversal curve diagrams of different SL and HZO capacitors at different states (initial, wake-up, fatigue, and recovery) were measured. The SL capacitors were found to effectively suppress the diffusion of defects during P-V cycling, resulting in improved fatigue stability characteristics and fatigue recovery capability compared to the HZO capacitor. Moreover, an improved switching speed of the SL films compared to the HZO capacitor was concluded based on the inhomogeneous field mechanism (IFM) model. These results indicate that the SL structure has a high potential in future high-speed ferroelectric memory applications with excellent stability and recovery capability.
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During forward swinging of the arm, the central nervous system must anticipate the effect of upraising upon the body. Little is known about the cerebellar network that coordinates these anticipatory postural adjustments (APAs). Stimulating different cerebellar regions with transcranial direct current stimulation (tDCS) and with different polarities modulated the APAs. We used surface electromyography (sEMG) to measure muscle activities in a bilateral rapid shoulder flexion task. The onset of APAs was altered after tDCS over the vermis, while the postural stability and the kinematics of arm raising were not affected. To our knowledge, this is the first human cerebellar-tDCS (c-tDCS) study to separate cerebellar involvement in core muscle APAs in bilateral rapid shoulder flexion. These data contribute to our understanding of the cerebellar network supporting APAs in healthy adults. Modulated APAs of the erector spinae by tDCS on the vermis may be related to altered cerebellar brain inhibition (CBI), suggesting the importance of the vermal-cerebral connections in APAs regulation.
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Estimulación Transcraneal de Corriente Directa , Adulto , Humanos , Músculo Esquelético/fisiología , Equilibrio Postural/fisiología , Electromiografía , Movimiento/fisiologíaRESUMEN
HfO2-based ferroelectric field-effect transistors (FeFETs) are a promising candidate for multilevel memory manipulation and brain-like computing due to the multi-domain properties of the HfO2FE films based polycrystalline structure. Although there have been many reports on the working mechanism of the HfO2-based FeFET and improving its reliability, the impact of multi-domain effect on the effective carrier mobility (µchannel) has not been carried out yet. The effectiveµchanneldetermines the level of readout current and affects the accuracy of the precision of peripheral circuit. In this work, FeFETs with HfZrOxFE gate dielectric were fabricated, and the effect of write (or erase) pulses with linear gradient variation on the effectiveµchannelwas studied. For the multiple downward polarization under write pulses, theµchanneldegrades as the domains gradually switch to downward. This is mainly due to the enhancement of the scattering effect induced by the positive charges (e.g. oxygen vacanciesVO2+) trapping and the increase of channel carrier density. For the erase pulses, theµchannelincreases as the domains gradually reverse to upward, which is mainly due to the reduction of the scattering effect induced by the detrapping of positive charges and the decrease of channel carrier density. In addition, the modulation effect of multilevel polarization states onµchannelis verified by numerical simulation. This effect provides a new idea and solution for the development of low power HfO2-based FeFETs in neuromorphic computing.
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INTRODUCTION: This study aimed to investigate the effect of cognitive load on anticipatory postural adjustment (APA) latency in patients with non-specific chronic low back pain (NCLBP) and its relationship with pain-related functional changes. METHODS: A cross-sectional study was conducted from December 15, 2022 to January 25, 2023. Participants were divided into a healthy control group (n = 29) and an NCLBP group (n = 29). Each group was assigned a single task of rapid arm raising and a dual task of rapid arm raising combined with a cognitive load. The cognitive load task was conducted using visual conflict. The APA latency for bilateral trunk muscles was observed using electromyography. The duration of electromyography recording in each task cycle was 28 s. Pain related-functional changes were evaluated using Roland-Morris Disability Questionnaire (RMDQ) before all tasks. RESULTS: The APA latency for the right multifidus was significantly delayed in the NCLBP group [25.38, 95% confidence interval (CI) 13.41-37.35] than in the healthy control group (- 5.80, 95% CI - 19.28 to 7.68) during dual task (p = 0.0416). The APA latency for the right multifidus (25.38, 95% CI 13.41-37.35) and transverse abdominis/internal oblique (29.15, 95% CI 18.81-39.50) were significantly delayed compared with on the left side in the NCLBP group during dual task (- 3.03, 95% CI - 15.18-9.13, p = 0.0220; 3.69, 95% CI - 6.81 to 14.18, p = 0.0363). The latency delay of the right and left multifidus APA in the NCLBP group under the dual-task was positively correlated with RMDQ scores (r = 0.5560, p = 0.0017; r = 0.4010, p = 0.0311). CONCLUSIONS: Cognitive load could induce APA delay in the right trunk muscles and co-activation pattern changes in bilateral trunk muscle APA in patients with NCLBP. The APA onset delay in multifidus is positively related to pain-related daily dysfunction. Trial Registration ChiCTR2300068580 (retrospectively registered in February 23, 2023).
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This study theoretically demonstrated the oxygen vacancy (VO2+)-based modulation of a tunneling junction memristor (TJM) with a high and tunable tunneling electroresistance (TER) ratio. The tunneling barrier height and width are modulated by the VO2+-related dipoles, and the ON and OFF-state of the device are achieved by the accumulation of VO2+ and negative charges near the semiconductor electrode, respectively. Furthemore, the TER ratio of TJMs can be tuned by varying the density of the ion dipoles (Ndipole), thicknesses of ferroelectric-like film (TFE) and SiO2 (Tox), doping concentration (Nd) of the semiconductor electrode, and the workfunction of the top electrode (TE). An optimized TER ratio can be achieved with high oxygen vacancy density, relatively thick TFE, thin Tox, small Nd, and moderate TE workfunction.
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Low back pain is a major global public health problem, but the current intervention effect is not ideal. A large body of previous literature suggests that patients with chronic low back pain may have abnormal postural control, which is more evident in the dual task situation. In recent years, research on postural control in patients with low back pain under dual-task conditions has gradually become a hot topic. However, the results obtained from these studies were not entirely consistent. In this review, we summarized relevant studies on the performance of postural control in patients with low back pain under dual-task conditions, analyze it from the perspective of the theoretical model of dual-task interaction, the specific research paradigm of dual task, the performance of postural control, and the related factors affecting postural control performance, etc. It was reasonable to assume that patients with low back pain might have a certain degree of abnormal postural control, and this abnormality was affected by comprehensive factors such as age, cognitive resource capacity, attention needs, complex sensorimotor integration, external environment, etc. Furthermore, postural control performance in low back pain patients under dual-task conditions was further influenced by the nature and complexity of the different tasks. In general, the more attention resources were needed, the external environmental conditions were worse, and the age-related functions were degenerate, etc., the weaker posture control ability was. In short, a deeper understanding of postural control in patients with low back pain under dual-task conditions may shed light on more references for the rehabilitation and management of low back pain, as well as some new ideas for scientific research on cognition and postural control.
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Background: It is reported that impaired postural control in patients with non-specific chronic low back pain (NCLBP) was associated with "core" trunk muscle incoordination. However, as the diaphragm is an important component of the "core" deep trunk muscle group, we still know little about the potential relationship between diaphragm dysfunction and NCLBP. Objectives: This case-control study is intended to investigate the changes of diaphragm morphological structure and function in young and middle-aged subjects with and without NCLBP by ultrasound evaluation and its possible validity in predicating the occurrence of NCLBP. Methods: 31 subjects with NCLBP (NCLBP group) and 32 matched healthy controls (HC group) were enrolled in this study. The diaphragm thickness at the end of inspiration (T ins) or expiration (T exp) during deep breathing was measured through B-mode ultrasound, and the diaphragm excursion (T exc) was estimated at deep breathing through M-mode ultrasound. The diaphragm thickness change rate (T rate) was calculated by the formula: T rate=(T ins - T exp)/T exp × 100%. Results: Compared with the HC group, the NCLBP group had a significant smaller degree of Tins (t = -3.90, P < 0.001), T exp (Z = -2.79, P=0.005), and T rate (t = -2.03, P=0.047). However, there was no statistical difference in T exc between the two groups (t = -1.42, P=0.161). The binary logistic regression analysis indicated that T rate (OR = 16.038, P=0.014) and T exp (OR = 7.714, P=0.004) were potential risk factors for the occurrence of NCLBP. Conclusions: The diaphragm morphological structure and function were changed in young and middle-aged subjects with NCLBP, while the diaphragm thickness change rate (T rate) and diaphragm thickness at the end of expiration (T exp) may be conductive to the occurrence of NCLBP. Furthermore, these findings may suggest that abnormal diaphragm reeducation is necessary for the rehabilitation of patients with NCLBP.
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Dolor de la Región Lumbar , Persona de Mediana Edad , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Estudios de Casos y Controles , Diafragma/diagnóstico por imagen , Diafragma/fisiología , Músculo Esquelético , UltrasonografíaRESUMEN
Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays a critical role in the native transportation of numerous drugs, metabolites, nutrients, and small molecules. HSA has been successfully used clinically as a noncovalent carrier for insulin (e.g., Levemir), GLP-1 (e.g., Liraglutide), and paclitaxel (e.g., Abraxane). Site-specific bioconjugation strategies for HSA only would greatly expand its role as the biocompatible, non-toxic platform for theranostics purposes. Using the enabling one-bead one-compound (OBOC) technology, we generated combinatorial peptide libraries containing myristic acid, a well-known binder to HSA at Sudlow I and II binding pockets, and an acrylamide. We then used HSA as a probe to screen the OBOC myristylated peptide libraries for reactive affinity elements (RAEs) that can specifically and covalently ligate to the lysine residue at the proximity of these pockets. Several RAEs have been identified and confirmed to be able to conjugate to HSA covalently. The conjugation can occur at physiological pH and proceed with a high yield within 1 h at room temperature. Tryptic peptide profiling of derivatized HSA has revealed two lysine residues (K225 and K414) as the conjugation sites, which is much more specific than the conventional lysine labeling strategy with N-hydroxysuccinimide ester. The RAE-driven site-specific ligation to HSA was found to occur even in the presence of other prevalent blood proteins such as immunoglobulin or whole serum. Furthermore, these RAEs are orthogonal to the maleimide-based conjugation strategy for Cys34 of HSA. Together, these attributes make the RAEs the promising leads to further develop in vitro and in vivo HSA bioconjugation strategies for numerous biomedical applications.
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Albúmina Sérica Humana , Albúmina Sérica , Humanos , Albúmina Sérica Humana/química , Albúmina Sérica/metabolismo , Lisina/metabolismo , Biblioteca de Péptidos , Péptidos/metabolismo , Unión ProteicaRESUMEN
Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24 h after intravascular injection of DCM-[PTX] at 5 mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2 Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6 Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.
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Micelas , Neoplasias de la Boca , Línea Celular Tumoral , Disulfuros , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/radioterapia , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Distribución TisularRESUMEN
Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3ß1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4ß1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.
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Neoplasias , Microambiente Tumoral , Animales , Inmunomodulación , Integrinas , Ratones , Neoplasias/tratamiento farmacológico , Linfocitos TRESUMEN
This work describes the discovery of a bead-bound membrane-active peptide (MAP), LBF127, that selectively binds fungal giant unilamellar vesicles (GUVs) over mammalian GUVs. LBF127 was re-synthesized in solution form and demonstrated to have antifungal activity with limited hemolytic activity and cytotoxicity against mammalian cells. Through systematic structure-activity relationship studies, including N- and C-terminal truncation, alanine-walk, and d-amino acid substitution, an optimized peptide, K-oLBF127, with higher potency, less hemolytic activity, and cytotoxicity emerged. Compared to the parent peptide, K-oLBF127 is shorter by three amino acids and has a lysine at the N-terminus to confer an additional positive charge. K-oLBF127 was found to have improved selectivity toward the fungal membrane over mammalian membranes by 2-fold compared to LBF127. Further characterizations revealed that, while K-oLBF127 exhibits a spectrum of antifungal activity similar to that of the original peptide, it has lower hemolytic activity and cytotoxicity against mammalian cells. Mice infected with Cryptococcus neoformans and treated with K-oLBF127 (16 mg/kg) for 48 h had significantly lower lung fungal burden compared to untreated animals, consistent with K-oLBF127 being active in vivo. Our study demonstrates the success of the one-bead, one-compound high-throughput strategy and sequential screening at identifying MAPs with strong antifungal activities.
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Antifúngicos , Cryptococcus neoformans , Animales , Antifúngicos/química , Antifúngicos/farmacología , Biblioteca de Genes , Hemólisis , Mamíferos , Ratones , Péptidos/química , Péptidos/farmacología , Relación Estructura-ActividadRESUMEN
In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.
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Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A-/-, CPT2-/-, ACAD9-/- cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.
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Antígeno CD47 , Glioblastoma , Animales , Antígeno CD47/metabolismo , Línea Celular Tumoral , Ácidos Grasos , Glioblastoma/genética , Glioblastoma/radioterapia , Humanos , Evasión Inmune , Ratones , FagocitosisRESUMEN
INTRODUCTION: Nonspecific chronic low back pain (NCLBP) is a leading contributor to disease burden worldwide, and the management of NCLBP has always been a problem. This study is designed to explore the feasibility and efficacy of m-health-based core stability exercise (CSE) combined with self-compassion training (SCT) and compare it with m-health-based CSE alone for the management of NCLBP. METHODS: This study is a pilot, patient-blinded randomized controlled trial. Participants with NCLBP were randomized into an intervention group and a control group. All the participants received m-health-based CSE, but those in the intervention group also received SCT before CSE. The intervention took place weekly on Saturday or Sunday for 4 weeks in total. Patients self-assessed their outcomes by filling out electronic questionnaires at 4 and 16 weeks after the start of the study. The primary outcome metrics for these questionnaires were back pain disability (based on the Roland-Morris Disability Questionnaire, RMDQ) and Pain intensity (Numeric Rating Scale, NRS; current pain, worst pain, average pain). The secondary outcome metrics were anxiety (GAD-7,7-item Generalized Anxiety Disorder scale), Depression Symptoms (PHQ-9,Patient Health Questionnaire-9), pain catastrophizing (PCS, Pain Catastrophizing Scale) and Self-efficiency (PSEQ, Pain Self-Efficiency Questionnaire). RESULTS: A total of 37 patients comprising 28 (75.7%) females completed the study, with 19 patients in the intervention group and 18 in the control group. The mean (SD) patient age was 35.2 (11.1) years. For all primary outcomes, although there were no significant differences between groups, we found that participants in the intervention group improved function and pain earlier. The RMDQ score changed by - 1.771 points (95% CI - 3.768 to 0.227) from baseline to 4 weeks in the control group and by - 4.822 points (95% CI - 6.752 to - 2.892) in the intervention group (difference between groups, - 3.052 [95% CI - 5.836 to - 0.267]). Also, the RMDQ score changed by - 3.328 points (95% CI - 5.252 to - 1.403) from baseline to 16 weeks in the control group and by - 5.124 points (95% CI - 7.014 to - 3.233) in the intervention group (difference between groups - 1.796 [95% CI - 4.501 to 0.909]). A similar pattern was found in the NRS scores. For secondary outcomes, the intervention group was superior to the control group in for GAD-7 (intervention difference from CSE along at week 16, - 2.156 [95% CI - 4.434 to - 0.122; P value for group effect was 0.030]). At the end of treatment, the improvement in PCS in the intervention group was significant (difference in PCS score at week 4, - 6.718 [95% CI - 11.872 to - 1.564]). We also found significant changes in PCS in the control group (- 6.326 [95% CI, - 11.250 to - 1.401]) at the 16-week follow-up. As for PSEQ, there were no apparent differences between the two groups. There were no adverse events relented to study participation. CONCLUSIONS: The pilot study is feasible to deliver, and our results indicate that participants in the group of m-health-based CSE combined with SCT may experience faster relief from pain intensity and back disability than those in the group of m-health-based CSE alone. TRIAL REGISTRATION: ChiCTR2100042810.
The impact of chronic low back pain on people's life quality and social economy is increasing year by year. Helping patients self-manage low back pain through a biological-psycho-social model seems to be an effective management approach, but the lack of connectivity between disciplines limits the development of multidisciplinary collaboration. Mindfulness-related therapy (self-compassion training) has been proven to be effective in chronic pain, and exercise therapy is widely used in rehabilitation medicine. In this study, these two programs were combined. We also used mobile health technology in the study, which brings a lot of convenience for research. The results of the study showed that the efficacy of the combined group seemed to be more obvious and worthy of further study.
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We demonstrate a non-volatile field-effect transistor (NVFET) with a 3-nm amorphous HfO2 dielectric that can simulate the synaptic functions under the difference and repetition of gate voltage (VG) pulses. Under 100 ns write/erase (W/E) pulse, a memory window greater than 0.56 V and cycling endurance above 106 are obtained. The storied information as short-term plasticity (STP) in the device has a spiking post-synaptic drain current (ID) that is a response to the VG input pulse and spontaneous decay of ID. A refractory period after the stimuli is observed, during which the ID hardly varies with the VG well-emulating the bio-synapse behavior. Short-term memory to long-term memory transition, paired-pulse facilitation, and post-tetanic potentiation are realized by adjusting the VG pulse waveform and number. The experimental results indicate that the amorphous HfO2 NVFET is a potential candidate for artificial bio-synapse applications.
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Background/Objective: The efficacy of transcranial magnetic stimulation (TMS) on Parkinson's disease (PD) varies across the stimulation targets. This study aims to estimate the effect of different TMS targets on motor symptoms in PD. Methods: A Bayesian hierarchical model was built to assess the effects across different TMS targets, and the rank probabilities and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine the ranks of each target. The primary outcome was the Unified Parkinson's Disease Rating Scale part-III. Inconsistency between direct and indirect comparisons was assessed using the node-splitting method. Results: Thirty-six trials with 1,122 subjects were included for analysis. The pair-wise meta-analysis results showed that TMS could significantly improve motor symptoms in PD patients. Network meta-analysis results showed that the high-frequency stimulation over bilateral M1, bilateral DLPFC, and M1+DLPFC could significantly reduce the UPDRS-III scores compared with sham conditions. The high-frequency stimulation over both M1 and DLPFC had a more significant effect when compared with other parameters, and ranked first with the highest SCURA value. There was no significant inconsistency between direct and indirect comparisons. Conclusion: Considering all settings reported in our research, high-frequency stimulation over bilateral M1 or bilateral DLPFC has a moderate beneficial effect on the improvement of motor symptoms in PD (high confidence rating). High-frequency stimulation over M1+DLPFC has a prominent beneficial effect and appears to be the most effective TMS parameter setting for ameliorating motor symptoms of PD patients (high confidence rating).