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Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.
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Hydrogen peroxide (H2O2) molecules play important roles in many green chemical reactions. However, the high activation energy limits their application efficiency, and there is still huge controversy about the activation path of H2O2 molecules over the presence of *OOH intermediates. Here, we confirmed the formation of the key species *OOH in the heterogeneous system, via in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), isotope labeling, and theoretical calculation. In addition, we found that compared with *H2O2, *OOH was more conducive to the charge transfer behavior with the catalyst and the activation of an O-O bond. Furthermore, we proposed to improve the local coordination structure and electronic density of the YFeO3 catalyst by regulating the surface relaxation with Ti modification so as to reduce the activation barrier of H2O2 and to improve the production efficiency of â¢OH. As a result, the kinetics rates of the Fenton-like (photo-Fenton) reaction had been significantly increased several times. The â¢OH free radical activity mechanism and molecular transformation pathways of 4-chloro phenol (4-CP) were also revealed. This may provide a clearer vision for the further study of H2O2 activation and suggest a means of designing catalysts for efficient H2O2 activation.
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Peróxido de Hidrógeno , Procesos Fotoquímicos , Catálisis , Peróxido de Hidrógeno/química , Hierro/química , Luz , FenolRESUMEN
Stem cells represent an attractive resource for cardiac regeneration. However, the survival and function of transplanted stem cells is poor and remains a major challenge for the development of effective therapies. As two main cell types currently under investigation in heart repair, mesenchymal stromal cells (MSCs) indirectly support endogenous regenerative capacities after transplantation, while induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) functionally integrate into the damaged myocardium and directly contribute to the restoration of its pump function. These two cell types are exposed to a common microenvironment with many stressors in ischemic heart tissue. This review summarizes the research progress on the mechanisms and challenges of MSCs and iPSC-CMs in post-MI heart repair, introduces several randomized clinical trials with 3D-mapping-guided cell therapy, and outlines recent findings related to the factors that affect the survival and function of stem cells. We also discuss the future directions for optimization such as biomaterial utilization, cell combinations, and intravenous injection of engineered nucleus-free MSCs.
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Procedimientos Quirúrgicos Cardíacos , Células Madre Pluripotentes Inducidas , Infarto del Miocardio , Humanos , Infarto del Miocardio/terapia , Trasplante de Células Madre , Miocitos CardíacosRESUMEN
Age-related cataract (ARC) is regarded as the principal cause of vision impairment among the aged. The regulatory role of long noncoding RNAs (LncRNAs) in ARC remains unclear. The lncRNA maternally expressed gene 3 (MEG3) has been reported to promote ARC progression, and the underlying mechanism was further investigated in this study. Lens epithelium samples were collected to verify the expression of MEG3. Lens epithelial cells (LECs) were treated with H2O2 to mimic microenvironment of ARC in vitro. Cell viability, reactive oxygen species, and ferroptosis were evaluated during the in viro experiments. In the present work, lncRNA MEG3 was highly expressed in ARC group, compared with normal group. MEG3 was induced, cell viability and glutathione peroxidase 4 (GPX4) level were inhibited, and ferroptosis was promoted in H2O2 treated LECs. LncRNA MEG3 silence reversed the effects of H2O2 on viability and ferroptosis in LECs. Thereafter, lncRNA MEG3 was found to bind to PTBP1 for GPX4 degradation. Silencing of GPX4 reversed the regulation of lncRNA MEG3 inhibition in H2O2-treated LECs. To sum up, lncRNA MEG3 exhibited high expression in ARC. In H2O2-induced LECs, inhibition of lncRNA MEG3 accelerated cell viability and repressed ferroptosis by interaction with PTBP1 for GPX4 messenger RNA decay. Targeting lncRNA MEG3 may be a novel treatment of ARC.
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Methylenecyclopropanes (MCPs) have emerged as versatile building blocks in synthetic chemistry because of their unique reactivity. However, metal-catalyzed hydrosilylation of MCPs has met with very limited successes. In this paper, catalytic selective hydrosilylations of MCPs with some primary silanes using an ene-diamido lanthanum ate complex as the catalyst were described. The catalytic reactions resulted in the selective formation of silacyclopentanes and (E)-homoallylsilanes, respectively, depending on the substituents on MCPs. The formation of silacyclopentanes via a catalytic cascade inter- and intramolecular hydrosilylation mechanism is strongly supported by the control and deuteration-labeling experiments and DFT calculations. The unique reactivity and selectivity could be attributed to the large lanthanum ion and ate structure of the catalyst.
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SUMMARY: We propose RabbitKSSD, a high-speed genome distance estimation tool. Specifically, we leverage load-balanced task partitioning, fast I/O, efficient intermediate result accesses, and high-performance data structures to improve overall efficiency. Our performance evaluation demonstrates that RabbitKSSD achieves speedups ranging from 5.7× to 19.8× over Kssd for the time-consuming sketch generation and distance computation on commonly used workstations. In addition, it significantly outperforms Mash, BinDash, and Dashing2. Moreover, RabbitKSSD can efficiently perform all-vs-all distance computation for all RefSeq complete bacterial genomes (455 GB in FASTA format) in just 2 min on a 64-core workstation. AVAILABILITY AND IMPLEMENTATION: RabbitKSSD is available at https://github.com/RabbitBio/RabbitKSSD.
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Genoma Bacteriano , Programas Informáticos , Evolución BiológicaRESUMEN
The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.
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Antivirales , Hígado Graso , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Resultado del Tratamiento , Seroconversión , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , ADN Viral/sangreRESUMEN
BACKGROUND AND AIMS: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all-cause and cause-specific mortality among MAFLD individuals of different genders. METHODS: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all-cause and cause-specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all-cause mortality. RESULTS: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all-cause and cause-specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004-1.014; female, HRs: 1.032, 95% CIs: 1.022-1.042). In males with MAFLD, a linear association with all-cause mortality was observed for weekly alcohol consumption (p for non-linearity = .21). Conversely, in females with MAFLD, the risk of all-cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non-linearity < .05). CONCLUSIONS: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all-cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.
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Consumo de Bebidas Alcohólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Masculino , Encuestas Nutricionales , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Conductas Relacionadas con la SaludRESUMEN
PURPOSE: A multivesicular liposome (MVL) is a liposomal vehicle designed to achieve sustained release characteristics for drugs with short half-lives. For example, a commercial MVL formulation of bupivacaine has been approved by the U.S. Food and Drug Administration for local and regional analgesia. For complex formulations like those containing MVLs, challenges in developing an in vitro release testing (IVRT) method may hinder generic development and regulatory approval. In this study, we developed an accelerated rotator-based IVRT method with the ability to discriminate bupivacaine MVLs with different quality attributes. METHODS: Three IVRT experimental setups including mesh tube, horizontal shaker, and vertical rotator were screened to ensure that at least 50% of bupivacaine can release from MVLs in 24 h. Sample dilution factors, incubation temperature, and the release media pH were optimized for the IVRT. The reproducibility of the developed IVRT method was validated with commercial bupivacaine MVLs. The discriminative capacity was assessed via comparing commercial and compromised bupivacaine MVL formulations. RESULTS: The rotator-based release setup was chosen due to the capability to obtain 70% of drug release within 24 h. The optimized testing conditions were chosen with a 50-fold dilution factor, a temperature of 37ºC, and a media pH of 7.4. CONCLUSIONS: An accelerated rotator-based IVRT method for bupivacaine MVLs was developed in this study, with the discriminatory ability to distinguish between formulations of different qualities. The developed IVRT method was a robust tool for generic development of MVL based formulations.
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Bupivacaína , Liposomas , Liberación de Fármacos , Preparaciones de Acción Retardada , Reproducibilidad de los ResultadosRESUMEN
Climate change-induced shifts in species phenology differ widely across trophic levels, which may lead to consumer-resource mismatches with cascading population and ecosystem consequences. Here, we examined the effects of different rainfall patterns (i.e., timing and amount) on the phenological asynchrony of population of a generalist herbivore and their food sources in semiarid steppe grassland in Inner Mongolia. We conducted a 10-y (2010 to 2019) rainfall manipulation experiment in 12 0.48-ha field enclosures and found that moderate rainfall increases during the early rather than late growing season advanced the timing of peak reproduction and drove marked increases in population size through increasing the biomass of preferred plant species. By contrast, greatly increased rainfall produced no further increases in vole population growth due to the potential negative effect of the flooding of burrows. The increases in vole population size were more coupled with increased reproduction of overwintered voles and increased body mass of young-of-year than with better survival. Our results provide experimental evidence for the fitness consequences of phenological mismatches at the population level and highlight the importance of rainfall timing on the population dynamics of small herbivores in the steppe grassland environment.
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Arvicolinae/crecimiento & desarrollo , Pradera , Lluvia , Animales , Arvicolinae/clasificación , Arvicolinae/fisiología , Biomasa , China , Cambio Climático , Conducta Alimentaria , Dinámica Poblacional , Probabilidad , Reproducción , Análisis de SupervivenciaRESUMEN
This research proposes a miniature circular polarization antenna used in a wireless capsule endoscopy system at 2.45 GHz for industrial, scientific, and medical bands. We propose a method of cutting a chamfer rectangular slot on a circular radiation patch and introducing a curved radiation structure into the centerline position of the chamfer rectangular slot, while a short-circuit probe is added to achieve miniaturization. Therefore, we significantly reduced the size of the antenna and made it exhibit circularly polarized radiation characteristics. A cross-slot is cut in the GND to enable the antenna to better cover the operating band while being able to meet the complex human environment. The effective axis ratio bandwidth is 120 MHz (2.38-2.50 GHz). Its size is π × 0.032λ02 × 0.007λ0 (where λ0 is the free-space wavelength of at 2.4 GHz). In addition, the effect of different organs such as muscle, stomach, small intestine, and big intestine on the antenna when it was embedded into the wireless capsule endoscopy (WCE) system was further discussed, and the results proved that the WCE system has better robustness in different organs. The antenna's specific absorption rate can follow the IEEE Standard Safety Guidelines (IEEE C95.1-1999). A prototype is fabricated and measured. The experimental results are consistent with the simulation results.
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Endoscopía Capsular , Diseño de Equipo , Tecnología Inalámbrica , Endoscopía Capsular/instrumentación , Endoscopía Capsular/métodos , Humanos , Tecnología Inalámbrica/instrumentación , Endoscopios en CápsulasRESUMEN
Winlevi® (clascoterone) topical cream (1%, w/w) was approved by the U.S. FDA for the treatment of acne vulgaris in patients 12 years of age and older. The active ingredient, clascoterone, is not stable in physiological solutions and can hydrolyze to cortexolone at body temperature. Instability of clascoterone poses a significant challenge in accurately assessing the rate and extent of clascoterone permeation in vitro. Therefore, the purpose of this study was to develop an in vitro skin permeation test (IVPT) method, and a robust analytical method, that can minimize hydrolyzation of clascoterone during the study for quantification of clascoterone. Two IVPT methods, using either vertical diffusion cells or flow-through cells, were developed and compared to evaluate in vitro permeation of clascoterone from Winlevi. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed to monitor the level of clascoterone and cortexolone in the IVPT samples. The analytical method features a 2-min high-throughput analysis with good linearity, selectivity, and showed a lower limit of quantitation (LLOQ) of 0.5 ng/mL for both clascoterone and cortexolone. The in vitro skin permeation of clascoterone and cortexolone was observed as early as 2 h in both IVPT methods. A substantive amount of clascoterone was found to hydrolyze to cortexolone when using the vertical static diffusion cells with aliquot sampling. Conversely, degradation of clascoterone was significantly minimized when using the flow-through diffusion cells with fractional sampling. The data enhanced our understanding of in vitro permeation of clascoterone following topical application of the Winlevi topical cream, 1% and underscores the importance of IVPT method development and optimization during product development.
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Cortodoxona , Absorción Cutánea , Crema para la Piel , Espectrometría de Masas en Tándem , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología , Crema para la Piel/farmacocinética , Crema para la Piel/administración & dosificación , Cortodoxona/administración & dosificación , Cortodoxona/farmacocinética , Cortodoxona/metabolismo , Cortodoxona/análogos & derivados , Espectrometría de Masas en Tándem/métodos , Piel/metabolismo , Administración Cutánea , Cromatografía Liquida/métodos , Animales , Permeabilidad , Porcinos , Humanos , PropionatosRESUMEN
The co-assembly naphthalimide/perylene diimide (NDINH/PDINH) supramolecular photocatalysts were successfully synthesized via a rapid solution dispersion method. A giant internal electric field (IEF) in co-assembly structure was built by the larger local dipole. NDINH coated on PDINH could reduce the reflected electric field over PDINH to improve its responsive activity to ultraviolet light. Resultantly, an efficient full-spectrum photocatalytic overall water splitting activity with H2 and O2 evolution rate of 317.2 and 154.8â µmol g-1 h-1 for NDINH/PDINH together with optimized O2 evolution rate with 2.61â mmol g-1 h-1 using AgNO3 as a sacrificial reagent were achieved. Meanwhile, its solar-to-hydrogen efficiency was enhanced to 0.13 %. The enhanced photocatalytic activity was primarily attributed to the IEF between NDINH and PDINH, significantly accelerating transfer and separation of photogenerated carriers. Additionally, a direct Z-Scheme pathway of carriers contributed to a high redox potential. The strategy provided a new perspective for the design of supramolecular photocatalysts.
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Lattice-oxygen activation has emerged as a popular strategy for optimizing the performance and selectivity of oxide-based thermocatalysis and electrolysis. However, the significance of lattice oxygen in oxide photocatalysts has been ignored, particularly in gas-solid reactions. Here, using methane oxidation over a Ru1@ZnO single-atom photocatalyst as the prototypical reaction and via 18O isotope labelling techniques, we found that lattice oxygen can directly participate in gas-solid reactions. Lattice oxygen played a dominant role in the photocatalytic reaction, as determined by estimating the kinetic constants in the initial stage. Furthermore, we discovered that dynamic diffusion between O2 and lattice oxygen proceeded even in the absence of targeted reactants. Finally, single-atom Ru can facilitate the activation of adsorbed O2 and the subsequent regeneration of consumed lattice oxygen, thus ensuring high catalyst activity and stability. The results provide guidance for next-generation oxide photocatalysts with improved activities and selectivities.
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As a holy grail in electrochemistry, both high-power and high-energy electrochemical energy storage system (EES) has always been a pursued dream. To simultaneously achieve the "both-high" EES, a rational design of structure and composition for storage materials with characteristics of battery-type and capacitor-type storage is crucial. Herein, fluorine-nitrogen co-implanted carbon tubes (FNCT) have been designed, in which plentiful active sites and expanded interlayer space have been created benefiting from the heteroatom engineering and the fluorine-nitrogen synergistic effect, thus the above two-type storage mechanism can get an optimal balance in the FNCT. The implanted fluorine heteroatoms can not only amplify interlayer spacing, but also induce the transformation of nitrogen configuration from pyrrole nitrogen to pyridine nitrogen, further promoting the activity of the carbon matrix. The extraordinary electrochemical performance as results can be witnessed for FNCT, which exhibit fast lithium-ion storage capability with a high energy density of 119.4 Wh kg-1 at an ultrahigh power density of 107.5 kW kg-1 .
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MOTIVATION: Detection and identification of viruses and microorganisms in sequencing data plays an important role in pathogen diagnosis and research. However, existing tools for this problem often suffer from high runtimes and memory consumption. RESULTS: We present RabbitV, a tool for rapid detection of viruses and microorganisms in Illumina sequencing datasets based on fast identification of unique k-mers. It can exploit the power of modern multi-core CPUs by using multi-threading, vectorization and fast data parsing. Experiments show that RabbitV outperforms fastv by a factor of at least 42.5 and 14.4 in unique k-mer generation (RabbitUniq) and pathogen identification (RabbitV), respectively. Furthermore, RabbitV is able to detect COVID-19 from 40 samples of sequencing data (255 GB in FASTQ format) in only 320 s. AVAILABILITY AND IMPLEMENTATION: RabbitUniq and RabbitV are available at https://github.com/RabbitBio/RabbitUniq and https://github.com/RabbitBio/RabbitV. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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COVID-19 , Virus , Algoritmos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Análisis de Secuencia de ADN , Programas Informáticos , Virus/genéticaRESUMEN
Long-acting injectable formulations based on poly(lactide-co-glycolide) (PLGA) have been commercialized for over 30 years in at least 20 FDA-approved products. These formulations offer several advantages, including reduced dosing frequency, improved patient compliance, and maintenance of therapeutic levels of drug. Despite extensive studies, the inherent complexity of the PLGA copolymer still poses significant challenges associated with the development of generic formulations having drug release profiles equivalent to those of the reference listed drugs. In addition, small changes to PLGA physicochemical properties or the drug product manufacturing process can have a major impact on the drug release profile of these long-acting formulations. This work seeks to better understand how variability in the physicochemical properties of similar PLGAs affects drug release from PLGA solid implants using Ozurdex (dexamethasone intravitreal implant) as the model system. Four 50:50, acid-terminated PLGAs of similar molecular weights were used to prepare four dexamethasone intravitreal implants structurally equivalent to Ozurdex. The PLGAs were extensively characterized by using a variety of analytical techniques prior to implant manufacture using a continuous, hot-melt extrusion process. In vitro release testing of the four structurally equivalent implants was performed in both normal saline and phosphate-buffered saline (PBS), yielding drastically different results between the two methods. In normal saline, no differences in the release profiles were observed. In PBS, the drug release profiles were sensitive to small changes in the residual monomer content, carboxylic acid end group content, and blockiness of the polymers. This finding further underscores the need for a physiologically relevant in vitro release testing method as part of a robust quality control strategy for PLGA-based solid implant formulations.
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Ácido Láctico , Ácido Poliglicólico , Humanos , Liberación de Fármacos , Ácido Poliglicólico/química , Ácido Láctico/química , Solución Salina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Dexametasona/químicaRESUMEN
Autophagy contributes to bone homeostasis and development under physiological conditions. Although previous studies have demonstrated the induction of the autophagy machinery by endogenous glucocorticoids (GCs), the precise mechanisms involved have not yet been clarified. The current study aimed to explore the effect of a low dose of GC (10-8 M dexamethasone, Dex) on autophagy in mouse embryonic osteoblastic precursor cells (MC3T3-E1 cells) and the potential mechanisms. The results showed that 10-8 M Dex induced significant time-dependent increases in the expression and activation of serum- and glucocorticoid-induced kinase-1 (SGK1) in MC3T3-E1 cells and that these effects were accompanied by increased cell viability and decreased apoptosis. The autophagy inhibitor 3-MA significantly inhibited Dex-mediated promotion of viability. Moreover, Dex increased LC3II and Beclin-1 levels and decreased SQSTM/p62 levels in a time-dependent manner, and these effects were attenuated by pretreatment with 3-MA. Transfection of Dex-treated MC3T3-E1 cells with shRNA-SGK1 resulted in a significant reduction in cell viability and an increase in apoptosis. 3-MA further exacerbated these effects of SGK1 inhibition. Knocking down SGK1 before Dex exposure significantly reduced the phosphorylated forkhead box O3a (p-FOXO3a)/FOXO3 ratio, suppressed LC3II and Beclin-1 levels, and increased SQSTM/p62 levels in MC3T3-E1 cells, and these effects were amplified by 3-MA. In conclusion, the results revealed that low-dose GC treatment increased osteoblast viability by activating autophagy via the SGK1/FOXO3a pathway.
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Dexametasona , Glucocorticoides , Animales , Ratones , Glucocorticoides/farmacología , Glucocorticoides/metabolismo , Dexametasona/farmacología , Beclina-1/metabolismo , Línea Celular , Transducción de Señal , Autofagia , Osteoblastos/metabolismo , ApoptosisRESUMEN
Intestinal fibrosis is one of the most severe complications of inflammatory bowel disease (IBD) and frequently requires surgery due to intestinal obstruction. Integrin αvß6, which is mainly regulated by the integrin ß6 subunit gene (ITGB6), is a special integrin subtype expressed only in epithelial cells. In our previous study, we found integrin αvß6 can promote the development of IBD, but the role of integrin αvß6 in intestinal fibrosis remains unclear. In this study, we observed a gradual increase of ITGB6 mRNA expression from normal region to stenotic region of IBD patients' intestinal specimens. Next, we established a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and a heterotopic intestinal transplant model, and found intestinal fibrosis was decreased in ITGB6-deficient mice compared to wild-type (WT) mice. Furthermore, we performed RNA-sequencing and KEGG pathway analysis on intestinal tissues from ITGB6-overexpressing transgenic mice and WT mice, and found multiple pathways containing ITGB6, are related to the activation of focal adhesion kinase (FAK); finding was confirmed by Western blot. At last, we generated a heterotopic intestinal transplant model found the FAK/AKT pathway was inhibited in ITGB6-deficient mice. In conclusion, our data demonstrate that integrin αvß6 promotes the pathogenesis of intestinal fibrosis by FAK/AKT pathway, making integrin αvß6 a potential therapeutic target to prevent this condition.
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Antígenos de Neoplasias/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Integrinas/metabolismo , Animales , Enfermedad de Crohn/etiología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Modelos Animales de Enfermedad , Femenino , Fibrosis , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/patología , Cadenas beta de Integrinas/genética , Cadenas beta de Integrinas/metabolismo , Integrinas/deficiencia , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Against the backdrop of global warming, rapid urbanization has caused the aggregation of urban building spaces and the heat island effect is becoming increasingly serious, hindering sustainable urban development. In order to investigate the potential and methods of green roofs in different types of neighborhoods to mitigate the urban heat island effect, this study used multivariate data for surface temperature inversion and local climate zone (LCZ), and the potential of green roofs to reduce the heat island effect was evaluated by combining LCZ zoning and ENVI-met prediction model. Finally, a multi-scenario analysis with economic factors was conducted to derive the optimal implementation path for green roofs. The results show that in LCZs 1-9, the green roof can reduce the daytime average air temperature by a maximum of 0.41 °C for 0.5 m of the LCZ8 roof and 0.37 °C for 1.2 m of the LCZ6 pedestrian. Based on the surface cooling efficiency of LCZ green roofs get the best green roof construction order: LCZ3, LCZ6, LCZ8 > LCZ2, LCZ5, LCZ7 > LCZ1, LCZ4, LCZ9. The construction of green roofs for the heat island areas within the fifth ring road of Beijing can reduce the area of high-temperature and sub-high-temperature zones by 52.55% and 29.17%, respectively, compared with the area without green roof construction. The study clarifies the technical methodology system of cooling efficiency of green roofs in different types of neighborhoods and the reduction of the urban-scale heat island effect, which provides a reference for the planning of green roofs for urban buildings.