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Exploring the intrinsic mechanisms of rare-earth ions entering the crystal phase has great significance for finely tuning the luminescent properties of glass-ceramics. Using Er3+ ions as a probe, X-ray diffraction was employed to precisely measure the crystallinity of SiO2-PbF2-Er2O3 glass-ceramics synthesized under various heat treatment conditions, confirming the occurrence of a rapid crystallization process. Additionally, by combining Judd-Ofelt theory with comprehensive analyses of absorption and fluorescence spectra, we calculated the relative proportions of Er3+ ions present in the crystal phase. We found that the crystallization process in the glass-ceramics and the incorporation of Er3+ ions into the crystal phase did not occur synchronously. This discovery provides new theoretical foundations and practical guidance for understanding the mechanism of rare-earth ion incorporation into crystal phases, which is significant for the development of functional materials with specific luminescent properties.
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Organic phase change material is an ideal solution to solve the heat dissipation problem of electronic devices. However, its low thermal conductivity limits its application. To solve this problem, a new porous aluminum skeleton/paraffin composite phase change material (AS-PCM) was prepared. The effects of porosity and porous aluminum skeletons on temperature control performance were explored. The experimental results show that the addition of AS significantly improves the thermal conductivity of organic PCM, and the thermal conductivity of AS-PCM is 32.3-59.6 times higher than that of pure paraffin. In addition, the temperature difference in AS-PCM with 75% porosity is 1-2 °C lower than that of AS-PCM with 85%, and 5-8 °C lower than that of AS-PCM with 95% porosity. The skeleton structure has an impact on the temperature control performance. The Mcc porous aluminum skeleton/paraffin composite phase change material (MAS-PCM) yields the best thermal performance compared with the Fcc porous aluminum skeleton/paraffin composite phase change material (FAS-PCM). The temperature control time of the MAS-PCM heat sink is increased by 5.3-50.8% relative to the FAS-PCM heat sink. The research results provide a novel approach for improving the thermal conductivity of PCMs.
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INTRODUCTION AND OBJECTIVES: Blood glucose fluctuates severely in the diabetes (DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels. MATERIALS AND METHODS: We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis. RESULTS: HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53. CONCLUSIONS: These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.
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Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Glucosa , Neoplasias Hepáticas , Neovascularización Patológica , Transducción de Señal , Transactivadores , Proteína p53 Supresora de Tumor , Factor A de Crecimiento Endotelial Vascular , Proteínas Reguladoras y Accesorias Virales , Humanos , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Glucosa/metabolismo , Línea Celular Tumoral , Células Hep G2 , Técnicas de Cocultivo , Virus de la Hepatitis B/genética , Microambiente Tumoral , AngiogénesisRESUMEN
CO poisoning in Pt-based anode catalysts significantly hampers the proton exchange membrane fuel cell (PEMFC) performance. Despite great advances in CO-tolerant catalysts, their effectiveness is often limited to fundamental three-electrode systems, which is inadequate for practical PEMFC applications. Herein, we present a straightforward thermal oxidation strategy for constructing a Ru oxide blocking layer on commercial PtRu/C through a one-step Ru-segregation-and-oxidation process. The resulting 0.7 nm thick Ru oxide layer effectively inhibits CO adsorption while maintaining hydrogen oxidation activity. PtRu@RuO2/C demonstrates exceptional CO tolerance, enduring 1% CO in rotating disk electrode tests, an â¼10-fold improvement compared to that of PtRu/C. Crucially, it retains high HOR activity and CO tolerance in PEMFC, with negligible polarization curve loss in the presence of 100 ppm CO. Notably, 85% HOR activity is retained after a 4 h stability test. This enhancement contributes to the Ru oxide layer decelerating CO adsorption kinetics, rather than promoting CO oxidation via the classic bifunctional mechanism.
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The incidence of urinary calculi in children has been increasing annually,and most of the cases are upper urinary tract stones.At present,surgery is the main way to treat upper urinary tract stones in children.With the gradual development of minimally invasive techniques in surgery,percutaneous nephrolithotomy,retrograde intrarenal surgery,and extracorporeal shock wave lithotripsy have become the main methods for treating upper urinary tract stones in children.We reviewed the current progress in surgical treatment of upper urinary tract stones in children and provided prospects for future treatment options.
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Nefrolitotomía Percutánea , Humanos , Niño , Nefrolitotomía Percutánea/métodos , Litotricia/métodos , Cálculos Urinarios/cirugía , Cálculos Urinarios/terapia , Cálculos Renales/cirugíaRESUMEN
Continuous-fiber-reinforced composite lattice structures (CFRCLSs) have garnered attention due to their lightweight and high-strength characteristics. Over the past two decades, many different topological structures including triangular, square, hexagonal, and circular units were investigated, and the basic mechanical responses of honeycomb structures under various load conditions, including tension, compression, buckling, shear, and fatigue were studied. To further improve the performance of the honeycombs, appropriate optimizations were also carried out. However, the mechanical properties of a single lattice often struggle to exceed the upper limit of its structure. This paper investigates the effect of permutation and hybrid mode on the mechanical properties of CFRCLSs by comparing five structures: rhomboid (R-type), octagon orthogonal array (OOA-type), octagon hypotenuse array (OHA-type), octagon nested array (ONA-type), and rhomboid circle (RC-type), with the conventional hexagonal structure (H-type). CFRCLS samples are fabricated using fused filament fabrication (FFF), with carbon-fiber-reinforced polylactic acid (PLA) as the matrix. The in-plane compression properties, energy absorption characteristics, and deformation behaviors of the hybrid structures were studied by experimental tests. The results demonstrate that different permutation and hybrid modes alter the deformation behaviors and mechanical properties of the structures. Taking elastic modulus as an example, the values of H-type, R-type, OOA-type, OHA-type, ONA-type, and RC-type are, respectively, 6.08 MPa, 5.76 MPa, 19.0 MPa, 10.3 MPa, 31.7 MPa, and 73.2 MPa, while the ratio of their masses is 1:1:1.10:1.52:1.66. Furthermore, hybrid lattice structures exhibit significantly improved mechanical properties compared to single lattice structures. Compared to the single structure R-type, the RC-type increases elastic modulus, yield strength, and energy absorption, respectively, by 12.7 times, 5.4 times, and 4.4 times.
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To satisfy the demand for efficient heat transfer, a novel three-dimensional overall jagged internal finned tube (3D-OJIFT) was fabricated, using the rolling-ploughing/extruding method. The thermal performance of the 3D-OJIFT were studied and compared in experiments and three-dimensional numerical simulations. The RNG k-ε turbulence model is well verified with the experimental results. By analyzing the distributions of velocity, temperature, and turbulence kinetic energy, it was found that the 3D-OJIFT destroyed the development of the velocity and thermal boundary layers, increased the turbulence disturbance, and reduced the temperature gradient, thus improving the heat transfer. The influences of the jagged height and jagged spiral angle of the 3D-OJIFT are discussed. The Nu and f increased as the jagged height of the 3D-OJIFT increased. The Nusselt number of the 3D-OJIFT was 1.67-2.04 times the value for the smooth tube. In addition, the comprehensive heat transfer performance of the 3D-OJIFT improved after increasing the jagged spiral angle. Compared with conventional internal helical-finned tubes and other reinforcement structures reported in the literature, the 3D-OJIFT demonstrated better comprehensive heat transfer performance. Finally, empirical correlations of the 3D-OJIFT were obtained.
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Wastewater pollutants are a major threat to natural resources, with antibiotics and heavy metals being common water contaminants. By harnessing clean, renewable solar energy, photocatalysis facilitates the synergistic removal of heavy metals and antibiotics. In this paper, MXene was both a template and raw material, and MXene-derived oxide (TiO2) and SnIn4S8 Z-scheme composite materials were synthesized and characterized. The synergistic mode of photocatalytic reduction and oxidation leads to the enhanced utilization of e-/h+ pairs. The TiO2/SnIn4S8 exhibited a higher photocatalytic capacity for the simultaneous removal of tetracycline (TC) (20 mg·L-1) and Cr(VI) (15 mg·L-1). The main active substances of TC degradation and Cr(VI) reduction were identified via free radical scavengers and electron paramagnetic resonance (EPR). Additionally, the potential photocatalytic degradation route of TC was thoroughly elucidated through liquid chromatography-mass spectrometry (LC-MS).
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Japanese encephalitis virus (JEV), a member of the Flaviviridae family and a flavivirus, is known to induce acute encephalitis. Vimentin protein has been identified as a potential receptor for JEV, engaging in interactions with the viral membrane protein. The Fc fragment, an integral constituent of immunoglobulins, plays a crucial role in antigen recognition by dendritic cells (DCs) or phagocytes, leading to subsequent antigen presentation, cytotoxicity, or phagocytosis. In this study, we fused the receptor of JEV vimentin with the Fc fragment of IgG and expressed the resulting vimentin-Fc fusion protein in Escherichia coli. Pull-down experiments demonstrated the binding ability of the vimentin-Fc fusion protein to JEV virion in vitro. Additionally, we conducted inhibition assays at the cellular level, revealing the ability of vimentin-Fc protein suppressing JEV replication, it may be a promising passive immunotherapy agent for JEV. These findings pave the way for potential therapeutic strategies against JEV.
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Nucleosome assembly during DNA replication is dependent on histone chaperones. Recent studies suggest that dysregulated histone chaperones contribute to cancer progression, including gastric cancer (GC). Further studies are required to explore the prognostic and therapeutic implications of histone chaperones and their mechanisms of action in GC progression. Here we identified histone chaperone ASF1B as a potential biomarker for GC proliferation and prognosis. ASF1B was significantly upregulated in GC, which was associated with poor prognosis. In vitro and in vivo experiments demonstrated that the inhibition of ASF1B suppressed the malignant characteristics of GC, while overexpression of ASF1B had the opposite effect. Mechanistically, transcription factor FOXM1 directly bound to the ASF1B-promoter region, thereby regulating its transcription. Treatment with thiostrepton, a FOXM1 inhibitor, not only suppressed ASF1B expression, but also inhibited GC progression. Furthermore, ASF1B regulated the mitochondrial protein peroxiredoxin 3 (PRDX3) transcription in a FOXM1-dependent manner. The crucial role of ASF1B-regulated PRDX3 in GC cell proliferation and oxidative stress balance was also elucidated. In summary, our study suggests that the FOXM1-ASF1B-PRDX3 axis is a potential therapeutic target for treating GC.
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Peroxiredoxina III , Neoplasias Gástricas , Humanos , Peroxiredoxina III/genética , Peroxiredoxina III/metabolismo , Neoplasias Gástricas/genética , Proteínas de Ciclo Celular/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Chaperonas de Histonas/metabolismo , Estrés Oxidativo , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
PURPOSE: To investigate the relationship between effective lens position (ELP) and patient characteristics, and to further develop a new intraocular lens (IOL) calculation formula for cataract patients with previous pars plana vitrectomy (PPV). DESIGN: Cross-sectional study. METHODS: A total of 2793 age-related cataract patients (group 1) and 915 post-PPV cataract patients (group 2) who underwent phacoemulsification with IOL implantation were included. The ELP of 2 groups was compared and the association between ELP and patient characteristics was further evaluated using standardized multivariate regression coefficients. An ensemble artificial intelligence-based ELP prediction model was developed using a training set of 810 vitrectomized eyes, and a thick-lens IOL formula (LISA-PPV) was constructed and compared with 7 existing formulas on an external multi-center testing set of 105 eyes. RESULTS: Compared to eyes with age-related cataract, vitrectomized eyes showed a similar ELP distribution (P = .19), but different standardized coefficients of preoperative biometry for ELP. The standardized coefficients also varied with the type of vitreous tamponade, history of scleral buckling, and ciliary sulcus IOL implantation. The LISA-PPV formula showed the lowest mean and median absolute prediction error (MAE: 0.63 D; MedAE: 0.44 D), and the highest percentages of eyes within ±0.5 D of prediction error (57.14%) in the testing dataset. CONCLUSIONS: The ELP prediction required optimization specifically for vitrectomized eyes based on their biometric and surgical characteristics. The LISA-PPV formula is a useful and accurate tool for determining IOL power in cataract patients with previous PPV (available at http://ppv-iolcalculator.com/).
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Inteligencia Artificial , Biometría , Implantación de Lentes Intraoculares , Lentes Intraoculares , Óptica y Fotónica , Facoemulsificación , Vitrectomía , Humanos , Estudios Transversales , Masculino , Femenino , Anciano , Vitrectomía/métodos , Biometría/métodos , Persona de Mediana Edad , Agudeza Visual/fisiología , Anciano de 80 o más Años , Refracción Ocular/fisiología , Catarata/fisiopatología , Catarata/complicaciones , Estudios RetrospectivosRESUMEN
Quantum effects in nanoscale electronic devices promise to lead to new types of functionality not achievable using classical electronic components. However, quantum behaviour also presents an unresolved challenge facing electronics at the few-nanometre scale: resistive channels start leaking owing to quantum tunnelling. This affects the performance of nanoscale transistors, with direct source-drain tunnelling degrading switching ratios and subthreshold swings, and ultimately limiting operating frequency due to increased static power dissipation. The usual strategy to mitigate quantum effects has been to increase device complexity, but theory shows that if quantum effects can be exploited in molecular-scale electronics, this could provide a route to lower energy consumption and boost device performance. Here we demonstrate these effects experimentally, showing how the performance of molecular transistors is improved when the resistive channel contains two destructively interfering waves. We use a zinc-porphyrin coupled to graphene electrodes in a three-terminal transistor to demonstrate a >104 conductance-switching ratio, a subthreshold swing at the thermionic limit, a >7 kHz operating frequency and stability over >105 cycles. We fully map the anti-resonance interference features in conductance, reproduce the behaviour by density functional theory calculations and trace back the high performance to the coupling between molecular orbitals and graphene edge states. These results demonstrate how the quantum nature of electron transmission at the nanoscale can enhance, rather than degrade, device performance, and highlight directions for future development of miniaturized electronics.
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Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.
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Oro , Hidrógeno , Nanopartículas del Metal , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/metabolismo , Hidrógeno/química , Catálisis , Animales , Oro/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Titanio/química , Ratones , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Nanocompuestos/químicaRESUMEN
When designing a molecular electronic device for a specific function, it is necessary to control whether the charge-transport mechanism is phase-coherent transmission or particle-like hopping. Here we report a systematic study of charge transport through single zinc-porphyrin molecules embedded in graphene nanogaps to form transistors, and show that the transport mechanism depends on the chemistry of the molecule-electrode interfaces. We show that van der Waals interactions between molecular anchoring groups and graphene yield transport characteristic of Coulomb blockade with incoherent sequential hopping, whereas covalent molecule-electrode amide bonds give intermediately or strongly coupled single-molecule devices that display coherent transmission. These findings demonstrate the importance of interfacial engineering in molecular electronic circuits.
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BACKGROUND AND AIMS: Interleukin 10 (IL-10) and natural killer (NK) cells have the potential to combat liver fibrosis. However, whether NK cells play an important role in the anti-fibrotic effects of IL-10 is not sufficiently elucidated. In this study, we investigated the regulatory effects of IL-10 on NK cells during liver fibrosis. METHODS: Fibrotic mice induced with carbon tetrachloride were treated with or without IL-10 in the presence or absence of NK cells. Liver damage and fibrosis were assessed using hematoxylin and eosin and Sirius Red staining and serum transaminase and liver hydroxyproline assays, respectively. NK cell distribution, quantity, activation, cytotoxicity, development, and origin were analyzed using immunohistochemistry, immunofluorescence, and flow cytometry. Enzyme-linked immunosorbent assay was used to determine chemokine levels. RESULTS: In the presence of NK cells, IL-10 gene intervention improved liver fibrosis and enhanced NK cell accumulation and function in the liver, as evidenced by increased NKG2D, interferon-γ, and CD107a expression. Furthermore, IL-10 promoted the migration of circulating NK cells to the fibrotic liver and elevated C-C motif ligand 5 levels. However, depletion of NK cells exacerbated liver fibrosis and impaired the anti-fibrotic effect of IL-10. CONCLUSIONS: The anti-fibrotic effect of IL-10 relies on the enhancement of NK cell immune function, including activation, cytotoxicity, development, and migration. These results provide valuable insights into the mechanisms through which IL-10 regulates NK cells to limit the progression of liver fibrosis.
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Interleucina-10 , Cirrosis Hepática , Animales , Ratones , Fibrosis , Inmunidad , Interleucina-10/metabolismo , Células Asesinas Naturales , Cirrosis Hepática/metabolismoRESUMEN
BACKGROUND: Gallbladder and biliary diseases (GABDs) are a major public health issue. AIM: To analysis the cause-specific incidence, prevalence, and years lived with disability (YLDs) and its temporal trends of GABDs at the global, regional, and national level. Data on GABD were available from the Global Burden of Disease study 2019. METHODS: The estimated annual percentage change (EAPC) was used to quantify temporal trend in GABD age-standardized incidence rates (ASIRs), age-standardized prevalence rate (ASPR), and age-standardized YLD rate (ASYR) by region, sex. We analyzed the relationship between the GABD burden and country development level using the human development index (HDI). RESULTS: In 2019, the incident cases of GABD were 52003772, with an ASIR of 63432/100000 population. Globally, the number of incident cases and ASIR of GABD increased 97% and 58.9% between 1990 and 2019. Although, the ASPR and ASYR decreased from 1990 to 2019, the number of prevalent and YLDs cases increased. The highest ASIR was observed in Italy, and the highest ASPR and ASYR was observed in United Kingdom. The highest burden of GABD was found in low-SDI region, and the burden in female was significantly higher than males. A generally negative correlation (ρ = -0.24, P < 0.05) of GABD with the EAPC and human development index (HDI) (in 2021) were observed for ASIR. What's more, no correlation in ASPR (ρ = -0.06, P = 0.39) and ASYR (ρ = -0.07, P = 0.36) of GABD with the EAPC and HDI (in 2021) were observed, respectively. CONCLUSION: GABD remain a major global public health challenge; however, the burden of GABD varies geographically. Globally, the number of incident cases and ASIR of GABD increased between 1990 and 2019. The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.
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An ideal implant needs to have the ability to coordinate the foreign body response and tissue regeneration. Here, Hydrogenated-silicon nanosheets (H-Si NSs) with favorable biodegradability are integrated and functionalized into a ß-tricalcium phosphate scaffold (H-Si TCP) for bone defect healing. H-Si TCP can greatly improve bone regeneration through osteoimmunomodulation-guided biodegradation in vivo. The spatiotemporal regulation of degradation products replenishes sufficient nutrients step by step for the entire process of bone repair. Extracellular and intracellular reactive oxygen species (ROS) are first downregulated by reaction with H-Si NSs, followed by marked M2 polarization, remodeling the micro-environment timely for immune-bone regeneration. The release of primary reaction products awakened bone marrow mesenchymal stem cells (BMSCs), which are converted into osteoblasts anchored on scaffolds. Subsequently, biomineralization is promoted by the final degradation products. The intrinsic ROS-responsive, immunoregulatory, and osteo-promotive capability of 2D H-Si NSs makes such composite H-Si TCP scaffold a highly potential alternative for the treatment of critical bone defect.
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OBJECTIVE: Acute-on-chronic liver failure (ACLF) causes organ system failures in patients and increases the risk of mortality. One of the main predictors of ACLF development in patients is the severity of systemic inflammation. The purpose of this study was to explore the effects of resolvin D1 (RvD1) on the rat model of ACLF. METHODS: The ACLF rats were induced by first intraperitoneally (ip) injecting CCl4 and porcine serum for 6 weeks to establish the chronic liver injury, followed by once administration (ip) of lipopolysaccharide and d-galactose d-GalN to cause acute liver injury (ALI). An hour before the ALI-induced treatment, rats were administrated (ip) with 0.9% saline or different doses of RvD1 (0.3 or 1 µg/kg). Afterward, the control and treated rats were killed and samples were collected. Biochemical analysis, hematoxylin-eosin and Sirius red staining, flow cytometry assay, and real-time polymerase chain reaction were used to assess the rat liver histopathological injury, the percentage of Treg cells in the spleen, and the messenger RNA (mRNA) levels of transcription factors and immunologic cytokines in liver. RESULTS: The necroinflammatory scores and the serum levels of transaminase significantly increased in ACLF rats compared with those in control rats. These impaired changes observed in ACLF rats could be attenuated by the administration of a low dose of RvD1 before the induction of ALI, which was associated with the increased proportion of regulatory T cells (Treg) in the spleen together with the increased gene expression ratio of Foxp3/RORγt and decreased mRNA level of Il-17a and Il-6 in the liver. CONCLUSION: A low dose of RvD1 can promote the resolution of inflammation in ACLF rats by increasing the proportion of Treg cells. RvD1, therefore, may be used as a potential drug for the treatment of patients with ACLF.
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Insuficiencia Hepática Crónica Agudizada , Linfocitos T Reguladores , Humanos , Ratas , Animales , Porcinos , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Insuficiencia Hepática Crónica Agudizada/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , ARN Mensajero/metabolismoRESUMEN
The progression of diabetes frequently results in a myriad of neurological disorders, including ischemic stroke, depression, blood-brain barrier impairment, and cognitive dysfunction. Notably, diabetes-associated cognitive impairment, a prevalent comorbidity during the course of diabetes, progressively affects patients' cognitive abilities and may reciprocally influence diabetes management, thereby severely impacting patients' quality of life. Extracellular vesicles, particularly nanoscale exosomes, have garnered considerable attention in recent years. These exosomes carry and transfer various functional molecules, such as proteins, lipids, and diverse non-coding RNAs, serving as novel regulators and communicators in intercellular interactions. Of particular interest, mesenchymal stem cell-derived exosomes (MSC-Exos) have been reported to traverse the blood-brain barrier and ameliorate intracerebral pathologies. This review elucidates the role of MSC-Exos in diabetes-related cognitive impairment, with a focus on their applications as biomarkers, modulation of neuronal regeneration and synaptic plasticity, anti-inflammatory properties, antioxidative effects, and their involvement in regulating the functionality of ß-amyloid proteins during the course of cognitive impairment. The immense therapeutic potential of MSC-Exos in the treatment of diabetes-induced cognitive dysfunction is emphasized.
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BACKGROUND: The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly understood. METHODS: We overexpressed deubiquitinase in cells overexpressing TXNIP and then detected the level of TXNIP to screen out the deubiquitinase regulating TXNIP; the interaction between TXNIP and deubiquitinase was verified by coimmunoprecipitation. After knockdown of a deubiquitinase and overexpression of TXNIP in Huh7 and HepG2 cells, lipopolysaccharide was used to establish a cellular inflammatory model to explore the role of deubiquitinase and TXNIP in hepatocyte inflammation. RESULTS: In this study, we discovered that ubiquitin-specific protease 5 (USP5) interacts with TXNIP and stabilizes it through deubiquitylation in Huh-7 and HepG2 cells after treatment with lipopolysaccharide. In lipopolysaccharide-treated Huh-7 and HepG2 cells, USP5 knockdown increased cell viability, reduced apoptosis, and decreased the expression of inflammatory factors, including NLRP3, IL-1ß, IL-18, ASC, and procaspase-1. Overexpression of TXNIP reversed the phenotype induced by knockdown USP5. CONCLUSIONS: In summary, USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.