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Ferroptosis plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to use a comprehensive bioinformatics approach and experimental validation to identify and verify potential ferroptosis-related genes in NAFLD. We downloaded the microarray datasets for screening differentially expressed genes (DEGs) and identified the intersection of these datasets with ferroptosis-related DEGs from the Ferroptosis database. Subsequently, ferroptosis-related DEGs were obtained using SVM analysis; the LASSO algorithm was then used to identify six marker genes. Furthermore, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Subsequently, we constructed drug regulatory networks and ceRNA regulatory networks. We identified six genes as marker genes for NAFLD, demonstrating their robust diagnostic abilities. Subsequent functional enrichment analysis results revealed that these marker genes were associated with multiple diseases and play a key role in NAFLD via the regulation of immune response and amino acid metabolism, among other pathways. The expression of hepatic EGR1, IL-6, SOCS1, and NR4A1 was significantly downregulated in the NAFLD model. Our findings provide new insights and molecular clues for understanding and treating NAFLD. Further studies are needed to assess the diagnostic potential of these markers for NAFLD.
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Biomarcadores , Biología Computacional , Ferroptosis , Enfermedad del Hígado Graso no Alcohólico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ferroptosis/genética , Biomarcadores/metabolismo , Humanos , Animales , Ratones , Perfilación de la Expresión Génica , Redes Reguladoras de GenesRESUMEN
CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.
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Many computational studies of catalytic surface reaction kinetics have demonstrated the existence of linear scaling relationships between physical descriptors of catalysts and reaction barriers on their surfaces. In this work, the relationship between catalyst activity, electronic structure, and alloy composition was investigated experimentally using a Ag x Pd1-x Composition Spread Alloy Film (CSAF) and a multichannel reactor array that allows measurement of steady-state reaction kinetics at 100 alloy compositions simultaneously. Steady-state H2-D2 exchange kinetics were measured at atmospheric pressure on Ag x Pd1-x catalysts over a temperature range of 333-593 K and a range of inlet H2 and D2 partial pressures. X-ray photoelectron spectroscopy (XPS) was used to characterize the CSAF by determining the local surface compositions and the valence band electronic structure at each composition. The valence band photoemission spectra showed that the average energy of the valence band, ÎµÌ v, shifts linearly with composition from -6.2 eV for pure Ag to -3.4 eV for pure Pd. At all reaction conditions, the H2-D2 exchange activity was found to be highest on pure Pd and gradually decreased as the alloy was diluted with Ag until no activity was observed for compositions with x Pd < 0.58. Measured H2-D2 exchange rates across the CSAF were fit using the Dual Subsurface Hydrogen (2H') mechanism to extract estimates for the activation energy barriers to dissociative adsorption, ΔE ads , associative desorption, ΔE des , and the surface-to-subsurface diffusion energy, ΔE ss, as a function of alloy composition, x Pd. The 2H' mechanism predicts ΔE ads = 0-10 kJ/mol, ΔE des = 30-65 kJ/mol, and ΔE ss = 20-30 kJ/mol for all alloy compositions with x Pd ≥ 0.64, including for the pure Pd catalyst (i.e., x Pd = 1). For these Pd-rich catalysts, ΔE des and ΔE ss appeared to increase by â¼5 kJ/mol with decreasing x Pd. However, due to the coupling of kinetic parameters in the 2H' mechanism, we are unable to exclude the possibility that the kinetic parameters predicted when x Pd ≥ 0.64 are identical to those predicted for pure Pd. This suggests that H2-D2 exchange occurs only on bulk-like Pd domains, presumably due to the strong interactions between H2 and Pd. In this case, the decrease in catalytic activity with decreasing x Pd can be explained by a reduction in the availability of surface Pd at high Ag compositions.
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Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
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Neoplasias , Receptores de IgG , Linfocitos T , Microambiente Tumoral , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Humanos , Animales , Ratones , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Linfocitos T/inmunología , Microambiente Tumoral/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Inmunoterapia Adoptiva/métodos , Receptor ErbB-2/inmunología , Receptor ErbB-2/antagonistas & inhibidores , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Femenino , Antígenos CD20/inmunologíaRESUMEN
Flexible light-emitting fibers and fabrics serve to bridge human-machine interactions. The desire for practical applications and the commercialization of flexible light-emitting fibers has accelerated structural progress and improvements. This review focuses on the structural design of light-emitting fibers and fabrics, starting with a summary of design principles, emission mechanisms, and structural evolution of coaxial structured light-emitting fibers. Subsequently, we explore recent advances in the helical structure design strategies that boost the mechanical sensitivity of light-emitting fibers. Following that, we analyze continuous preparation processes and the development of large-area intelligent light-emitting fabrics based on interwoven structures. Examples based on stiff and rigid inorganic-based light-emitting diodes integrated into flexible systems are also presented. Finally, we discuss the current challenges and future opportunities for light-emitting applications in the field of wearable and smart devices.
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Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations, which result in premature termination codons (PTCs) in coding sequence, leading to truncated, often nonfunctional proteins. Suppressor tRNAs can recognize and pair with these PTCs, allowing the ribosome to continue translation and produce a full-length protein. This review introduces the mechanism and development of suppressor tRNAs, compares suppressor tRNAs with other readthrough therapies, discusses their potential for clinical therapy, limitations, and obstacles. We also summarize the applications of suppressor tRNAs in both in vitro and in vivo, offering new insights into the research and treatment of nonsense mutation diseases.
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Global population growth and industrialization have exacerbated the nonrenewable energy crises and environmental issues, thereby stimulating an enormous demand for producing environmentally friendly materials. Typically, biomass-based aerogels (BAs), which are mainly composed of biomass materials, show great application prospects in various fields because of their exceptional properties such as biocompatibility, degradability, and renewability. To improve the performance of BAs to meet the usage requirements of different scenarios, a large number of innovative works in the past few decades have emphasized the importance of micro-structural design in regulating macroscopic functions. Inspired by the ubiquitous random or regularly arranged structures of materials in nature ranging from micro to meso and macro scales, constructing different microstructures often corresponds to completely different functions even with similar biomolecular compositions. This review focuses on the preparation process, design concepts, regulation methods, and the synergistic combination of chemical compositions and microstructures of BAs with different porous structures from the perspective of gel skeleton and pore structure. It not only comprehensively introduces the effect of various microstructures on the physical properties of BAs, but also analyzes their potential applications in the corresponding fields of thermal management, water treatment, atmospheric water harvesting, CO2 absorption, energy storage and conversion, electromagnetic interference (EMI) shielding, biological applications, etc. Finally, we provide our perspectives regarding the challenges and future opportunities of BAs. Overall, our goal is to provide researchers with a thorough understanding of the relationship between the microstructures and properties of BAs, supported by a comprehensive analysis of the available data.
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Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.
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Acné Vulgar , Glycyrrhiza , Nanopartículas , Polisacáridos , Dióxido de Silicio , Glycyrrhiza/química , Dióxido de Silicio/química , Polisacáridos/química , Polisacáridos/farmacología , Nanopartículas/química , Animales , Porosidad , Acné Vulgar/tratamiento farmacológico , Ratones , Administración Tópica , Humanos , Portadores de Fármacos/química , Liberación de Fármacos , Indoles , PolímerosRESUMEN
There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (ORâ =â 1.053, 95% CI: 1.016-1.090, Pâ =â .004). Similarly, the presence of breast cancer may increase the risk of IBD (ORâ =â 1.111, 95% CI: 1.035-1.194, Pâ =â .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (ORâ =â 1.050, 95% CI: 1.020-1.080, Pâ <â .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (ORâ =â 1.106, 95% CI: 1.011-1.209, Pâ =â .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.
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Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Femenino , Enfermedad de Crohn/genética , Enfermedad de Crohn/epidemiología , Enfermedades Inflamatorias del Intestino/genética , Colitis Ulcerosa/genética , Colitis Ulcerosa/epidemiología , Factores de Riesgo , Polimorfismo de Nucleótido SimpleRESUMEN
Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08â s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65â MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.
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As a popular nutritional enhancer, casein phosphopeptides (CPPs) have attracted growing attention in food industry. However, conventional methods for CPPs detection are usually less precise or requires expensive instruments. Herein, a nanozyme-based colorimetric method was developed to achieve the quantitative detection of CPPs in food samples. This method is based on a facilely fabricated peroxidase-like nanozyme (Fe@UiO-66), which combines the specific binding of CPPs, as well as the nanozyme-catalyzed colorimetric sensing that can be easily detected by spectrometer. The method displayed good quantitative ability toward CPPs with the linear range of 2-30 µg/mL, the low limit of detection of 0.267 µg/mL and limit of quantification of 1.335 µg/mL. We highlighted the specificity, anti-interference and practicability of this method, by investigating the performances toward food samples. Besides, a smartphone-based colorimetric sensing platform was also established, which is conducive to the portable detection. The developed nanozyme-based colorimetric sensing method provides a promising strategy for CPPs detection in food samples.
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Caseínas , Colorimetría , Fosfopéptidos , Colorimetría/métodos , Caseínas/análisis , Caseínas/química , Fosfopéptidos/análisis , Análisis de los Alimentos/métodos , Límite de Detección , Estructuras Metalorgánicas/química , AnimalesRESUMEN
In this work, corn straw was used as raw material, Hummers method and activation were used to adjust the graphite structure in biochar, and preparing straw based biochar (H-BCS) with ultra-high specific surface area (3441.80 m2/g), highly total pore volume (1.9859 cm3/g), and further enhanced physicochemical properties. Compared with untreated straw biochar (BCS), the specific surface area and total pore volume of H-BCS were increased by 47.24 % and 55.85 %, respectively. H-BCS showed good removal ability in subsequent experiments by using chloramphenicol (CP), hexavalent chromium (Cr6+), and crystal violet (CV) as adsorption models. In addition, the adsorption capacities of H-BCS (CP: 1396.30 mg/g, Cr6+: 218.40 mg/g, and CV: 1246.24 mg/g) are not only higher than most adsorbents, even after undergoing 5 cycles of regeneration, its adsorption capacity remains above 80 %, indicating significant potential for practical applications. In addition, we also speculated and analyzed the conjecture about the "graphite-structure regulation" during the preparation process, and finally discussed the possible mechanism during the adsorption processes. We hope this work could provide a new strategy to solve the restriction of biochar performance by further exploring the regulation of graphite structure in carbon materials.
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Carbón Orgánico , Grafito , Contaminantes Químicos del Agua , Carbón Orgánico/química , Grafito/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Adsorción , Eliminación de Residuos Líquidos/métodos , Cromo/química , Contaminación del Agua/prevención & control , Zea mays/química , Purificación del Agua/métodosRESUMEN
Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.
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Antivirales , Modelos Animales de Enfermedad , Virus de la Hepatitis B , Hepatitis B , Replicación Viral , Humanos , Animales , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Antivirales/uso terapéutico , Antivirales/farmacología , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Hepatitis B/inmunología , Replicación Viral/efectos de los fármacos , Ratones , Hepatocitos/virologíaRESUMEN
Herein, we demonstrate a simple, homogenous and label-free electrochemical biosensing system for sensitive nucleic acid detection based on target-responsive porous materials and nuclease-triggered target recycling amplification. The Fe(CN)63- reporter was firstly sealed into the pores of Fe3O4 nanoparticles by probe DNA. Target DNA recognition triggered the controllable release of Fe(CN)63- for the redox reaction with the electron mediator of methylene blue enriched in the dodecanethiol assembled electrode and thereby generating electrochemical signal. The exonuclease III (Exo III)-assisted target recycling and the catalytic redox recycling between Fe(CN)63- and methylene blue contributed for the enhanced signal response toward target recognition. The low detection limit toward target was obtained as 478 fM and 1.6 pM, respectively, by square wave voltammetry and cyclic voltammetry methods. It also possessed a well-discrimination ability toward mismatched strands and high tolerance to complex sample matrix. The coupling of bio-gated porous nanoparticles, nuclease-assisted target amplification and catalytic redox recycling afforded the sensing system with well-controllable signal responses, sensitive and selective DNA detection, and good stability, reusability and reproducibility. It thus opens a new avenue toward the development of simple but sensitive electrochemical biosensing platform.
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Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Límite de Detección , Oxidación-Reducción , Técnicas Biosensibles/métodos , ADN/química , Técnicas Electroquímicas/métodos , Catálisis , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/química , Azul de Metileno/químicaRESUMEN
The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.
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AIMS: Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. METHODS: To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 24 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. KEY FINDINGS: The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. SIGNIFICANCE: PIM1 alleviated mice liver oxidative stress and NAFLD induced by high-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.
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Hemo-Oxigenasa 1 , Ratones Endogámicos C57BL , NAD(P)H Deshidrogenasa (Quinona) , Factor 2 Relacionado con NF-E2 , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-pim-1 , Animales , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/genética , Hemo-Oxigenasa 1/metabolismo , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Transducción de Señal , Apoptosis , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genéticaRESUMEN
In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al.1.
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Tejido Adiposo , Organoides , Animales , Organoides/citología , Tejido Adiposo/citología , Células del Estroma/citología , Rumiantes , Técnicas de Cultivo de Célula/métodos , Neovascularización Fisiológica/fisiología , Adipogénesis/fisiología , Adipocitos/citología , Células CultivadasRESUMEN
Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.
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Enfermedades Autoinmunes del Sistema Nervioso , Encefalitis , Enfermedad de Hashimoto , Humanos , Autoanticuerpos , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológicoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Chronic activation of endoplasmic reticulum stress (ERS) in hepatocytes may promote the development of NAFLD, yet endoplasmic reticulum stress-related genes (ERSGs) have not been studied in NAFLD. Our aim is to study the relationship between ERSGs and the immune microenvironment of NAFLD patients and to construct predictive models. We screened 48 endoplasmic reticulum stress-related differentially expressed genes (ERSR-DEGs) using data from two GEO datasets and the GeneCards database. Enrichment analysis revealed that ERSR-DEGs are closely associated with immune-related pathways and functions. The immune infiltration profile of NAFLD was obtained by single sample gene set enrichment analysis (ssGSEA). There were significant differences in immune cell infiltration and immune function between NAFLD group and control group. Using 113 NAFLD samples, we explored two molecular clusters based on ERSR-DEGs. A five-gene SVM model was selected as the best machine learning model, and a nomogram based on five-gene SVM model showed good predictive efficiency. The mRNA expression levels of POR, PPP1R15A, FOS and FAS were significantly different between NAFLD mice and healthy mice. In conclusion, ERS is closely associated with the development of NAFLD. We established a promising and SVM-based predictive model to assess the risk of disease in patients with ERS subtypes and NAFLD.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estrés del Retículo Endoplásmico/genética , HepatocitosRESUMEN
This study presents the development of a sensitive and simple enhanced ratiometric fluorescence sensing platform in the consist of CdTe quantum dots (QDs), carbon dots (CDs), and hepatitis B core antibody labeled with horseradish peroxidase (HBcAb-HRP) for the visual analysis of H2O2 and glucose. The sulfur atoms in HBcAb-HRP have a strong affinity for Cd(II), which effectively enhances the fluorescence intensity of the CdTe QDs due to the generation of more radiative centers at the CdTe/Cd-SR complex. In the presence of H2O2, the Cd-S bonds are oxidized to form disulfide products and results in linear fluorescence quenching, while CDs maintain stable. Becasue glucose can be converted into H2O2 with the aid of glucose oxidase, this sensing platform can also be used for analyzing glucose. The detection limits for H2O2 and glucose are 2.9 µmol L-1 with RSD of 2.6% and 1.6 µmol L-1 with RSD of 2.4% respectively. In addition, under UV lamp irradiation, the orange-yellow CdTe QDs gradually quench with increasing H2O2 and glucose, while the blue CDs remain unchanged. A color change from orange-yellow to blue enables a visual semi-quantitative determination of H2O2 in commercial contact lens solution and glucose in human serum without any pretreatment. Thus, this CdTe QDs/CDs ratiometric sensing platform has significant potential for the rapid analysis of H2O2 and glucose in actual application.