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BACKGROUND: The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. OBJECTIVE: This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC. METHODS: Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. RESULTS: The combination of anlotinib with an anti-PD-1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF-1α signaling axis. CD8+ T-cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti-PD-1 therapy in patients with HCC. CONCLUSIONS: Our findings highlight anlotinib's potential to augment the efficacy of anti-PD-1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14-mediated CD8+ T-cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. HIGHLIGHTS: Synergistic effects of anlotinib and anti-PD-1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF-1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T-cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti-PD-1-based therapies in advanced HCC patients.
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Linfocitos T CD8-positivos , Carcinoma Hepatocelular , Inmunoterapia , Indoles , Neoplasias Hepáticas , Quinolinas , Receptores de Transferrina , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Animales , Ratones , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Indoles/farmacología , Indoles/uso terapéutico , Humanos , Inmunoterapia/métodos , Receptores de Transferrina/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
Fringe projection profilometry (FPP) faces significant challenges regarding calibration difficulty and stitching error accumulation when operating across scenes ranging from tens to hundreds of meters. This Letter presents a calibration-free 3D measurement method by integrating a binocular vision of a FPP scanner with a wide field-of-view (FoV) vision that constructs global benchmarks to unify local 3D scanning and global 3D stitching, which is adaptable to arbitrarily large-scale scenes. A posterior global optimization model is then established to determine the reconstruction parameters and stitching poses simultaneously at each scanning node with adaptively distributed benchmarks. Consequently, the integrated vision measurement system not only eliminates the large-scale pre-calibration and stitching error accumulation but also overcomes system structural instability during moving measurement. With the proposed method, we achieved 3D measurements with an accuracy of 0.25 mm and a density of 0.5 mm for over 50-m-long scenes.
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Background: The efficacy of anti-TNF therapy in Crohn's disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes. Methods: In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A > G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals. Results: A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18-2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78-3.68, P < 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59-3.06, P < 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers. Conclusions: HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.
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BACKGROUND: To explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery. METHODS: A total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group. RESULTS: By comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1-2 (mild degeneration subgroup) and 10 hip joints with Grade 3-4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images. CONCLUSION: 3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course.
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Acetábulo , Artroplastia de Reemplazo de Cadera , Cartílago Articular , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Acetábulo/diagnóstico por imagen , Acetábulo/patología , Anciano , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Anciano de 80 o más Años , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/patología , Índice de Severidad de la EnfermedadRESUMEN
Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.
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The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.
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Cardiac arrest is a common and fatal emergency situation. Recently, an increasing number of studies have shown that anemia in patients with cardiac arrest is closely related to high mortality rates and poor neurological outcomes. Anemia is prevalent among patients with post-cardiac arrest syndrome (PCAS), but its specific pathogenesis remains unclear. The mechanisms may involve various factors, including reduced production of erythropoietin, oxidative stress/inflammatory responses, gastrointestinal ischemic injury, hepcidin abnormalities, iatrogenic blood loss, and malnutrition. Measures to improve anemia related to cardiac arrest may include blood transfusions, administration of erythropoietin, anti-inflammation and antioxidant therapies, supplementation of hematopoietic materials, protection of gastrointestinal mucosa, and use of hepcidin antibodies and antagonists. Therefore, exploring the latest research progress on the mechanisms and treatment of anemia related to cardiac arrest is of significant guiding importance for improving secondary brain injury caused by anemia and the prognosis of patients with cardiac arrest.
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Anemia , Paro Cardíaco , Humanos , Anemia/etiología , Anemia/terapia , Paro Cardíaco/terapia , Paro Cardíaco/etiología , Paro Cardíaco/complicaciones , Eritropoyetina/uso terapéutico , Hepcidinas/metabolismo , Estrés Oxidativo , Síndrome de Paro Post-Cardíaco/complicaciones , Síndrome de Paro Post-Cardíaco/etiología , Síndrome de Paro Post-Cardíaco/terapiaRESUMEN
The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.
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Proteínas Adaptadoras Transductoras de Señales , Carcinogénesis , Transactivadores , Factores de Transcripción , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Proteínas Señalizadoras YAP , Humanos , Proteínas Señalizadoras YAP/metabolismo , Proteínas Señalizadoras YAP/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Carcinogénesis/genética , Línea Celular Tumoral , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Animales , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Ratones , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Proteínas con Dominio LIMRESUMEN
Elevated levels of atmospheric molecular chlorine (Cl2) have been observed during the daytime in recent field studies in China but could not be explained by the current chlorine chemistry mechanisms in models. Here, we propose a Cl2 formation mechanism initiated by aerosol iron photochemistry to explain daytime Cl2 formation. We implement this mechanism into the GEOS-Chem chemical transport model and investigate its impacts on the atmospheric composition in wintertime North China where high levels of Cl2 as well as aerosol chloride and iron were observed. The new mechanism accounts for more than 90% of surface air Cl2 production in North China and consequently increases the surface air Cl2 abundances by an order of magnitude, improving the model's agreement with observed Cl2. The presence of high Cl2 significantly alters the oxidative capacity of the atmosphere, with a factor of 20-40 increase in the chlorine radical concentration and a 20-40% increase in the hydroxyl radical concentration in regions with high aerosol chloride and iron loadings. This results in an increase in surface air ozone by about 10%. This new Cl2 formation mechanism will improve the model simulation capability for reactive chlorine abundances in the regions with high emissions of chlorine and iron.
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Aerosoles , Atmósfera , Cloro , Hierro , Oxidación-Reducción , Cloro/química , China , Hierro/química , Atmósfera/química , Contaminantes Atmosféricos/química , FotoquímicaRESUMEN
Molecular-based magnetic materials are expected to serve as building blocks for quantum bits. To realize high-dimensional Hilbert space and addressability, we constructed anisotropic multi-level systems based on CuII and VIV with orthogonal magnetic orbitals. The crystal structures and intramolecular magnetic couplings of four CuIIVOII complexes [{CuVO(appen)2}2], [{CuVO(fhma)2EDA}2], [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n are characterized. Due to the orthogonal magnetic orbitals of CuII and VIV, the Cu-V pairs in the four complexes have strong ferromagnetic couplings, and the coupling strength is linearly related to the dihedral angle between the two equatorial planes of the two coordination polyhedra. Because of the triplet ground state, the system can be described by an effective Hamiltonian model consisting of two S = 1 spins coupled together. The anisotropy parameters of [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n were obtained by the simulation of X-band continuous wave electron paramagnetic resonance (cw-EPR) spectra, confirming that both complexes have zero-field splitting addressable on the relative energy scale. The results indicate that constructing multi-centre complexes based on orthogonal magnetic orbitals is a promising strategy for designing multidimensional quantum bits.
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Objective: To explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II). Materials and Methods: A total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM. Results: There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p<0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013-1.052, p<0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag. Conclusion: 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer.
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Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
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Etanol , Neuronas GABAérgicas , Ratones Endogámicos C57BL , Colículos Superiores , Área Tegmental Ventral , Animales , Colículos Superiores/efectos de los fármacos , Colículos Superiores/fisiología , Etanol/farmacología , Masculino , Ratones , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/fisiología , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismoRESUMEN
BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.
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Fatiga , Diálisis Peritoneal , Humanos , Masculino , Femenino , Diálisis Peritoneal/efectos adversos , Persona de Mediana Edad , Adulto , China/epidemiología , Fatiga/etiología , Ansiedad/etiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Prurito/etiología , Anciano , Evaluación de Síntomas , Análisis Factorial , Estudios Transversales , Pueblos del Este de AsiaRESUMEN
Thermophilic semi-continuous composting (TSC) is effective for kitchen waste (KW) treatment, but large amounts of NH3-rich odorous gas are generated. This study proposes a TSC-biofiltration (BF) two-stage process. Compost from the front-end TSC was used as the packing material in the BF to remove NH3 from the exhaust gas. The BF process was effective in removing up to 83.7 % of NH3, and the NH3 content was reduced to < 8 ppm. Seven days of BF improved the quality of the product from TSC by enhancing the germination index to 134.6 %, 36.5 % higher than that in the aerated-only group. Microbial community analysis revealed rapid proliferation and eventual dominance in the BF of members related to compost maturation and the nitrogen cycle from Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidetes. The results suggest that the TSC-BF two-stage process is effective in reducing NH3 emissions from TSC and improving compost quality.
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Amoníaco , Compostaje , Fertilizantes , Compostaje/métodos , Filtración/métodos , Eliminación de Residuos/métodos , Temperatura , Suelo/química , Bacterias/metabolismoRESUMEN
Gastrodin, an anti-inflammatory herbal agent, is known to suppress microglia activation. Here, we investigated whether it would exert a similar effect in reactive astrocytes and whether it might act through the renin-angiotensin system (RAS) and sirtuin 3 (SIRT3). Angiotensinogen (ATO), angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) and type 2 (AT2) receptor and SIRT3 expression was detected in TNC-1 astrocytes treated with BV-2 microglia conditioned medium (CM) with or without gastrodin and lipopolysaccharide (LPS) pre-treatment by RT-PCR, immunofluorescence and western blotting analysis. Expression of C3 (A1 astrocyte marker), S100A10 (A2 astrocyte marker), proinflammatory cytokines and neurotrophic factors was then evaluated. The results showed a significant increase of ATO, ACE, AT1, SIRT3, C3, proinflammatory cytokines and neurotrophic factors expression in TNC-1 astrocytes incubated in CM + LPS when compared with cells incubated in the CM, but AT2 and S100A10 expression was reduced. TNC-1 astrocytes responded vigorously to BV-2 CM treated with gastrodin + LPS as compared with the control. This was evident by the decreased expression of the abovementioned protein markers, except for AT2 and S100A10. Interestingly, SIRT3, IGF-1 and BDNF expression was enhanced, suggesting that gastrodin inhibited the expression of RAS and proinflammatory mediators but promoted the expression of neurotrophic factors. And gastrodin regulated the phenotypic changes of astrocytes through AT1. Additionally, azilsartan (a specific inhibitor of AT1) inhibited the expression of C3 and S100A10, which remained unaffected in gastrodin and azilsartan combination treatment. These findings provide evidence that gastrodin may have a therapeutic effect via regulating RAS-SIRT3.
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Astrocitos , Alcoholes Bencílicos , Glucósidos , Microglía , Sistema Renina-Angiotensina , Sirtuina 3 , Glucósidos/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Animales , Alcoholes Bencílicos/farmacología , Ratones , Sirtuina 3/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Lipopolisacáridos/farmacología , Mediadores de Inflamación/metabolismo , Citocinas/metabolismo , Línea CelularRESUMEN
Bismaleimide (BMI) is often used as the cross-linking reagent in Diels-Alder (D-A)-type intrinsic self-healing materials (DISMs) to promote the connectivity of damaged surfaces based on reversible D-A bond formation on the molecular scale. Until now, although DISMs have exhibited great potential in the applications of various sensors, electronic skin, and artificial muscles, it is still difficult to prepare DISMs with satisfactory self-healing abilities and high tensile strengths and strains at the same time, thus largely limiting their applications in self-healing anticorrosive coatings. Herein, symmetrical trimaleimide (TMI) was successfully synthesized, and trimaleimide-structured D-A self-healing polyurethane (TMI-DA-PU) was prepared via the reversible D-A reaction (cycloaddition of furan and maleimide). As a DISM, TMI-DA-PU exhibits apparently higher self-healing efficiency (98.7%), tensile strength (25.4 MPa), and strain (1378%) compared to bismaleimide-structured D-A self-healing polyurethane (BMI-DA-PU) (self-healing efficiency, 90.2%; tensile strength, 19.3 MPa; strain, 1174%). In addition, TMI-DA-PU shows a high recycling efficiency (>95%) after 4 cycles of recycling. A series of characterizations indicate that TMI provides more monoene rings as the self-healing sites, forms denser cross-linked structures compared to BMI, and is, thus, more appropriate to be used for DISM applications. Moreover, the barrier abilities of coatings can be semi-quantitatively expressed by the impedance value at 0.01 Hz (|Z|0.01 Hz). The |Z|0.01â¯Hz value of the TMI-DA-PU coating is 3.93 × 109 Ω cm2 on day 0, which is significantly higher than that of the BMI-DA-PU coating (6.76 × 108 Ω cm2 on day 0), indicating that the denser rigid cross-linked structure of TMI results in the small porosity in the TMI-DA-PU coating, thus effectively improving the anticorrosion performance. The construction of DISMs with the structure of TMI demonstrates immense potential in self-healing anticorrosive coatings.
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The object detection method serves as the core technology within the unmanned driving perception module, extensively employed for detecting vehicles, pedestrians, traffic signs, and various objects. However, existing object detection methods still encounter three challenges in intricate unmanned driving scenarios: unsatisfactory performance in multi-scale object detection, inadequate accuracy in detecting small objects, and occurrences of false positives and missed detections in densely occluded environments. Therefore, this study proposes an improved object detection method for unmanned driving, leveraging Transformer architecture to address these challenges. First, a multi-scale Transformer feature extraction method integrated with channel attention is used to enhance the network's capability in extracting features across different scales. Second, a training method incorporating Query Denoising with Gaussian decay was employed to enhance the network's proficiency in learning representations of small objects. Third, a hybrid matching method combining Optimal Transport and Hungarian algorithms was used to facilitate the matching process between predicted and actual values, thereby enriching the network with more informative positive sample features. Experimental evaluations conducted on datasets including KITTI demonstrate that the proposed method achieves 3% higher mean Average Precision (mAP) than that of the existing methodologies.
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Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.