RÉSUMÉ
BACKGROUND: Post-burn anxiety and depression affect considerably the quality of life and recovery of patients; however, limited research has demonstrated risk factors associated with the development of these conditions. AIM: To predict the risk of developing post-burn anxiety and depression in patients with non-mild burns using a nomogram model. METHODS: We enrolled 675 patients with burns who were admitted to The Second Affiliated Hospital, Hengyang Medical School, University of South China between January 2019 and January 2023 and met the inclusion criteria. These patients were randomly divided into development (n = 450) and validation (n = 225) sets in a 2:1 ratio. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with post-burn anxiety and depression diagnoses, and a nomogram model was constructed. RESULTS: Female sex, age < 33 years, unmarried status, burn area ≥ 30%, and burns on the head, face, and neck were independent risk factors for developing post-burn anxiety and depression in patients with non-mild burns. The nomogram model demonstrated predictive accuracies of 0.937 and 0.984 for anxiety and 0.884 and 0.923 for depression in the development and validation sets, respectively, and good predictive performance. Calibration and decision curve analyses confirmed the clinical utility of the nomogram. CONCLUSION: The nomogram model predicted the risk of post-burn anxiety and depression in patients with non-mild burns, facilitating the early identification of high-risk patients for intervention and treatment.
RÉSUMÉ
Introduction: Both rheumatoid arthritis (RA) and rosacea represent common chronic systemic autoimmune conditions. Recent research indicates a heightened RA risk among individuals with rosacea. However, the molecular mechanisms linking these diseases remain largely unknown. This study aims to uncover shared molecular regulatory networks and immune cell infiltration patterns in both rosacea and RA. Methods: The gene expression profiles of RA (GSE12021, GSE55457), and the rosacea gene expression profile (GSE6591), were downloaded from Gene Expression Omnibus (GEO) databases, and obtained to screen differentially expressed genes (DEGs) by using "limma" package in R software. Various analyses including GO, KEGG, protein-protein interaction (PPI) network, and weighted gene co-expression network analyses (WGCNA) were conducted to explore potential biological functions and signaling pathways. CIBERSORT was used to assess the abundance of immune cells. Pearson coefficients were used to calculate the correlations between overlapped genes and the leukocyte gene signature matrix. Flow cytometry (FCM) analysis confirmed the most abundant immune cells detected in rheumatoid arthritis and rosacea. Receiver operator characteristic (ROC) analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to confirm biomarkers and functions. Results: Two hundred seventy-seven co-expressed DEGs were identified from these datasets. Functional enrichment analysis indicated that these DEGs were associated with immune processes and chemokine-mediated signaling pathways. Fourteen and 17 hub genes overlapped between cytoHubba and WGCNA were identified in RA and rosacea, respectively. Macrophages and dendritic cells were RA and rosacea's most abundant immune cells, respectively. The ROC curves demonstrated potential diagnostic values of CXCL10 and CCL27, showing higher levels in the serum of patients with RA or rosacea, and suggesting possible regulation in the densities and functions of macrophages and dendritic cells from RA and rosacea, which were validated by FCM and qRT-PCR. Conclusion: Importantly, our findings may contribute to the scientific basis for biomarkers and therapeutic targets for patients with RA and rosacea in the future.
RÉSUMÉ
BACKGROUNDS: Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. METHODS: Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. RESULTS: The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. CONCLUSIONS: In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.
Sujet(s)
Amyotrophie , Protéines plasmatiques de liaison au rétinol , Transduction du signal , Animaux , Protéines plasmatiques de liaison au rétinol/métabolisme , Souris , Amyotrophie/métabolisme , Amyotrophie/étiologie , Protéines membranaires/métabolisme , Souris knockout , Modèles animaux de maladie humaine , Facteur de transcription STAT-3/métabolisme , Muscles squelettiques/anatomopathologie , Muscles squelettiques/métabolisme , Mâle , Kinase Janus-2/métabolismeRÉSUMÉ
Sulfonamide antibiotics (SAs) widely used have potentially negative effects on human beings and ecosystems. Adsorption and advanced oxidation methods have been extensively applied in SAs wastewater treatment. In this study, compared with Al3+@BC500 and Fe3+@BC500, La3+@BC500 for activating persulfate (S2O82-) had the best effect removal performance of sulfadiazine (SDZ) and sulfamethoxazole (SMX). Morphology, acidity, oxygen-containing functional groups, and loading of La3+@BC500 were analyzed by techniques, including EA, BET, XRD, XPS, FT-IR. XRD results show that with the increase of La3+ loading, the surface characteristics of biochar gradually changed from CaCO3 to LaCO3OH. Through EPR technology, it is proved that LaCO3OH on the surface of La3+@BC500 can not only activate S2O82- to generate SO4-â¢, but also to produce â¢OH. In the optimization experiment, the optimal dosage of La3+ is between 0.05 and 0.2 (mol/L)/g. SDZ had a good removal effect at pH (5-9), but SMX had a good removal effect only at pH=3. Zeta potential also proves that the material is more stable under acidic conditions. The removal process of SDZ is more in accord with pseudo-first-order kinetics (R2=0.9869), while SMX is more in line with pseudo-second order kinetics (R2=0.9926).
Sujet(s)
Antibactériens , Lanthane , Sulfonamides , Polluants chimiques de l'eau , Polluants chimiques de l'eau/composition chimique , Antibactériens/composition chimique , Sulfonamides/composition chimique , Lanthane/composition chimique , Charbon de bois/composition chimique , Adsorption , Élimination des déchets liquides/méthodes , Purification de l'eau/méthodes , Eaux usées/composition chimiqueRÉSUMÉ
Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere cell culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.
Sujet(s)
Différenciation cellulaire , Hématopoïèse , Cellules souches hématopoïétiques , Danio zébré , Animaux , Cellules souches hématopoïétiques/effets des médicaments et des substances chimiques , Cellules souches hématopoïétiques/cytologie , Cellules souches hématopoïétiques/métabolisme , Souris , Différenciation cellulaire/effets des médicaments et des substances chimiques , Hématopoïèse/effets des médicaments et des substances chimiques , Récepteurs Notch/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Corps embryoïdes/cytologie , Corps embryoïdes/effets des médicaments et des substances chimiques , Corps embryoïdes/métabolisme , Cils vibratiles/métabolisme , Cils vibratiles/effets des médicaments et des substances chimiques , Blastomères/cytologie , Blastomères/métabolisme , Blastomères/effets des médicaments et des substances chimiques , Cellules cultivéesRÉSUMÉ
Electrochemical carbon dioxide/carbon monoxide reduction reaction offers a promising route to synthesize fuels and value-added chemicals, unfortunately their activities and selectivities remain unsatisfactory. Here, we present a general surface molecular tuning strategy by modifying Cu2O with a molecular pyridine-derivative. The surface modified Cu2O nanocubes by 4-mercaptopyridine display a high Faradaic efficiency of greater than 60% in electrochemical carbon monoxide reduction reaction to acetate with a current density as large as 380 mA/cm2 in a liquid electrolyte flow cell. In-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy reveals stronger *CO signal with bridge configuration and stronger *OCCHO signal over modified Cu2O nanocubes by 4-mercaptopyridine than unmodified Cu2O nanocubes during electrochemical CO reduction. Density function theory calculations disclose that local molecular tuning can effectively regulate the electronic structure of copper catalyst, enhancing *CO and *CHO intermediates adsorption by the stabilization effect through hydrogen bonding, which can greatly promote asymmetric *CO-*CHO coupling in electrochemical carbon monoxide reduction reaction.
RÉSUMÉ
The aging process of microplastics (MPs) could significantly change their physical and chemical characteristics and impact their migration behavior in soil. However, the complex effects of different cations and humic acids (HA) on the migration of aged MPs through saturated media are not clear. In this research, the migration and retention of pristine/aged PSMPs (polystyrene microplastics) under combined effects of cations (Na+, Ca2+) (ionic strength = 10 mM) and HA (0, 5, 15 mg/L) were investigated and analyzed in conjunction with the two-site kinetic retention model and DLVO theory. The findings showed that the aging process accelerated PSMPs migration under all tested conditions. Aged PSMPs were less susceptible to Ca2+ than pristine PSMPs. Under Ca2+ conditions, pristine/aged PSMPs showed higher retention than under Na+ conditions in the absence of HA. Furthermore, under Na+ conditions, the migration of aged PSMPs significantly increased at higher concentrations of HA. However, under Ca2+ conditions, the migration of aged PSMPs decreased significantly at higher concentrations of HA. In higher HA conditions, HA, Ca2+, and PSMPs interact to cause larger aggregations, resulting in the sedimentation of aged PSMPs. The DLVO calculations and two-site kinetic retention models' results showed the detention of PSMPs was irreversible under higher HA conditions (15 mg/L) with Ca2+, and aged PSMPs were more susceptible to clogging. These findings may help to understand the potential risk of migration behavior of PSMPs in the soil-groundwater environment.
Sujet(s)
Cations , Substances humiques , Microplastiques , Polystyrènes , Polystyrènes/composition chimique , Microplastiques/toxicité , Cations/composition chimique , Porosité , Cinétique , Sol/composition chimiqueRÉSUMÉ
The interaction effects between the main components (proteins (P), carbohydrates (C), and lipids (L)) of protein-rich biomass during microwave-assisted pyrolysis were investigated in depth with an exploration of individual pyrolysis and copyrolysis (PC, PL, and CL) of model compounds. The average heating rate of P was higher than those of C and L, and the interactions in all copyrolysis groups reduced the max instant heating rate. The synergistic extent (S) of PC and PL for bio-oil yield was 16.78 and 18.24%, respectively, indicating that the interactions promoted the production of bio-oil. Besides, all of the copyrolysis groups exhibited a synergistic effect on biochar production (S = 19.43-28.24%), while inhibiting the gas generation, with S ranging from -20.17 to -6.09%. Regarding the gaseous products, apart from H2, P, C, and L primarily generated CO2, CO, and CH4, respectively. Regarding bio-oil composition, the interactions occurring within PC, PL, and CL exhibited a significantly synergistic effect (S = 47.81-412.96%) on the formation of N-heterocyclics/amides, amides/nitriles, and acids/esters, respectively. Finally, the favorable applicability of the proposed interaction effects was verified with microalgae. This study offers valuable insights for understanding the microwave-assisted pyrolysis of protein-rich biomass, laying the groundwork for further research and process optimization.
Sujet(s)
Biomasse , Micro-ondes , Pyrolyse , Protéines/composition chimique , Lipides/composition chimique , Charbon de bois/composition chimique , Glucides/composition chimique , BiocarburantsRÉSUMÉ
Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy.
Sujet(s)
Mucopolysaccharidoses , Spectrométrie de masse en tandem , Humains , Mucopolysaccharidoses/diagnostic , Mucopolysaccharidoses/métabolisme , Spectrométrie de masse en tandem/méthodes , Marqueurs biologiques/métabolisme , Glycosaminoglycanes/métabolismeRÉSUMÉ
BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.
Sujet(s)
Marqueurs biologiques , Méthylation de l'ADN , Facteur de croissance fibroblastique de type 2 , Muscles squelettiques , Courbe ROC , Sarcopénie , Sujet âgé , Femelle , Humains , Mâle , Marqueurs biologiques/sang , Ilots CpG , Facteur de croissance fibroblastique de type 2/sang , Facteur de croissance fibroblastique de type 2/génétique , Muscles squelettiques/métabolisme , Sarcopénie/diagnostic , Sarcopénie/génétiqueRÉSUMÉ
A modified biodegradable plastic (PLA/PBAT) was developed by through covalent bonding with proteinase K, porcine pancreatic lipase, or amylase, and was then investigated in anaerobic co-digestion mixed with food waste. Fluorescence microscope validated that enzymes could remain stable in modified the plastic, even after co-digestion. The results of thermophilic anaerobic co-digestion showed that, degradation of the plastic modified with Proteinase K increased from 5.21 ± 0.63 % to 29.70 ± 1.86 % within 30 days compare to blank. Additionally, it was observed that the cumulative methane production increased from 240.9 ± 0.5 to 265.4 ± 1.8 mL/gVS, and the methane production cycle was shortened from 24 to 20 days. Interestingly, the kinetic model suggested that the modified the plastic promoted the overall hydrolysis progression of anaerobic co-digestion, possibly as a result of the enhanced activities of Bacteroidota and Thermotogota. In conclusion, under anaerobic co-digestion, the modified the plastic not only achieved effective degradation but also facilitated the co-digestion process.
Sujet(s)
Matières plastiques biodégradables , Méthane , Anaérobiose , Méthane/métabolisme , Matières plastiques biodégradables/composition chimique , Dépollution biologique de l'environnement , Triacylglycerol lipase/métabolisme , Suidae , Animaux , Aliments , Déchets , Amylases/métabolisme , Cinétique , Hydrolyse , Élimination des déchets/méthodes ,RÉSUMÉ
The highly stable biomass structure formed by cellulose, hemicellulose, and lignin results in incomplete conversion and carbonization under hydrothermal conditions. In this study, pretreated corn straw hydrochar (PCS-HC) was prepared using a low-temperature alkali/urea combination pretreatment method. The Mass loss rate of cellulose, hemicellulose, and lignin from pretreated biomass, as well as the effects of the pretreatment method on the physicochemical properties of PCS-HC and the adsorption performance of PCS-HC for alkaline dyes (rhodamine B and methylene blue), were investigated. The results showed that the low-temperature NaOH/urea pretreatment effectively disrupted the stable structure formed by cellulose, hemicellulose, and lignin. NaOH played a dominant role in solubilizing cellulose and the combination of low temperature and urea enhanced the ability of NaOH to remove cellulose, hemicellulose, and lignin. Compared to the untreated hydrochar, PCS-HC exhibited a rougher surface, a more abundant pore structure, and a larger specific surface area. The unpretreated hydrochar exhibited an adsorption capacity of 64.8% for rhodamine B and 66.32% for methylene blue. However, the removal of rhodamine B and methylene blue by PCS-BC increased to 89.12% and 90.71%, respectively, under the optimal pretreatment conditions. The PCS-HC exhibited a favorable adsorption capacity within the pH range of 6-9. However, the presence of co-existing anions such as Cl-, SO42-, CO32-, and NO3- hindered the adsorption capacity of PCS-HC. Among these anions, CO32- exhibited the highest level of inhibition. Chemisorption, including complexation, electrostatic attraction, and hydrogen bonding, were the primary mechanism for dye adsorption by PCS-HC. This study provides an efficient method for utilizing agricultural waste and treating dye wastewater.
Sujet(s)
Hydroxyde de sodium , Urée , Eaux usées , Polluants chimiques de l'eau , Adsorption , Hydroxyde de sodium/composition chimique , Urée/composition chimique , Eaux usées/composition chimique , Polluants chimiques de l'eau/composition chimique , Agents colorants/composition chimique , Lignine/composition chimique , Cellulose/composition chimique , Rhodamines/composition chimique , TempératureRÉSUMÉ
BACKGROUND: Robot-assisted radical prostatectomy (RARP) has emerged as a pivotal surgical intervention for the treatment of prostate cancer (PCa). However, the complexity of clinical cases, heterogeneity of PCa, and limitations in physician expertise pose challenges to rational decision-making in RARP. To address these challenges, the authors aimed to organize the knowledge of previously complex cohorts and establish an online platform named the RARP knowledge base (RARPKB) to provide reference evidence for personalized treatment plans. MATERIALS AND METHODS: PubMed searches over the past two decades were conducted to identify publications describing RARP. The authors collected, classified, and structured surgical details, patient information, surgical data, and various statistical results from the literature. A knowledge-guided decision-support tool was established using MySQL, DataTable, ECharts, and JavaScript. ChatGPT-4 and two assessment scales were used to validate and compare the platform. RESULTS: The platform comprised 583 studies, 1589 cohorts, 1 911 968 patients, and 11 986 records, resulting in 54 834 data entries. The knowledge-guided decision support tool provide personalized surgical plan recommendations and potential complications on the basis of patients' baseline and surgical information. Compared with ChatGPT-4, RARPKB outperformed in authenticity (100% vs. 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), matching of patients (100% vs. 0%), and personalized recommendations for complications (100% vs. 20%). Postuse, the average System Usability Scale score was 88.88±15.03, and the Net Promoter Score of RARPKB was 85. The knowledge base is available at: http://rarpkb.bioinf.org.cn . CONCLUSIONS: The authors introduced the pioneering RARPKB, the first knowledge base for robot-assisted surgery, with an emphasis on PCa. RARPKB can assist in personalized and complex surgical planning for PCa to improve its efficacy. RARPKB provides a reference for the future applications of artificial intelligence in clinical practice.
Sujet(s)
Prostatectomie , Tumeurs de la prostate , Interventions chirurgicales robotisées , Humains , Mâle , Interventions chirurgicales robotisées/méthodes , Tumeurs de la prostate/chirurgie , Prostatectomie/méthodes , Bases de connaissances , Médecine de précision/méthodes , Techniques d'aide à la décision , Systèmes d'aide à la décision cliniqueRÉSUMÉ
Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the major regions regulating cognitive and emotional behaviors, and found that the neuronal deletion of GHSR reduced DIO-induced neuroinflammation by suppressing proinflammatory chemokines/cytokines and decreasing microglial activation. Furthermore, our data showed that neuronal GHSR deletion suppresses neuroinflammation by downregulating AMPK-autophagy signaling in neurons. In conclusion, our data reveal that neuronal GHSR inhibition protects against DIO-induced depressive-like behavior and spatial cognitive dysfunction, at least in part, through AMPK-autophagy signaling-mediated neuroinflammation.
Sujet(s)
AMP-Activated Protein Kinases , Récepteurs à la ghréline , Animaux , Souris , Dépression/génétique , Alimentation riche en graisse/effets indésirables , Inflammation/complications , Maladies neuro-inflammatoires , Neurones , Obésité/complications , Récepteurs à la ghréline/génétiqueRÉSUMÉ
In2O3 has been found a promising application in CO2 hydrogenation to methanol, which is beneficial to the utilization of CO2. The oxygen vacancy (Ov) site is identified as the catalytic active center of this reaction. However, there remains a great challenge to understand the relations between the state of oxygen species in In2O3 and the catalytic performance for CO2 hydrogenation to methanol. In the present work, we compare the properties of multiple In2O3 and Ir-promoted In2O3 (Ir-In2O3) catalysts with different Ir loadings and after being pretreated under different reduction temperatures. The CO2 conversion rate of Ir-In2O3 is more promoted than that of pure In2O3. With only a small amount of Ir loading, the highly dispersed Ir species on In2O3 increase the concentration of Ov sites and enhance the activity. By finely tuning the catalyst structure, Ir-In2O3 with an Ir loading of 0.16 wt.% and pre-reduction treatment under 300°C exhibits the highest methanol yield of 146 mgCH3OH/(gcat·hr). Characterizations of Raman, electron paramagnetic resonance, X-ray photoelectron spectroscopy, CO2-temperature programmed desorption and CO2-pulse adsorption for the catalysts confirm that more Ov sites can be generated under higher reduction temperature, which will induce a facile CO2 adsorption and desorption cycle. Higher performance for methanol production requires an adequate dynamic balance among the surface oxygen atoms and vacancies, which guides us to find more suitable conditions for catalyst pretreatment and reaction.
Sujet(s)
Dioxyde de carbone , Méthanol , Hydrogénation , Catalyse , OxygèneRÉSUMÉ
BACKGROUND AND AIMS: Coronary heart disease (CHD) is a condition that carries a high risk of mortality and is associated with aging. CHD is characterized by the chronic inflammatory response of the coronary intima. Recent studies have shown that the methylation level of blood mononuclear cell DNA is closely associated with adverse events in CHD, but the roles and mechanisms of DNA methylation in CHD remain elusive. METHODS AND RESULTS: In this study, the DNA methylation status within the epigenome of human coronary tissue in the sudden coronary death (SCD) group and control (CON) group of coronary heart disease was analyzed using the Illumina® Infinium Methylation EPIC BeadChip (850 K chip), resulting in the identification of a total of 2553 differentially methylated genes (DMGs). The differentially methylated genes were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and significant differential DNA methylation was found. Among the differentially hypomethylated genes were GAL-8, LTF, and RFPL3, while the highly methylated genes were TMEM9B, ANK3, and C6orF48. These genes were mainly enriched in 10 significantly enriched pathways, such as cell adhesion junctions, among which the differentially methylated gene GAL-8 was involved in inflammatory pathway signaling. For functional analysis of GAL-8, we first examined the differences in GAL-8 promoter methylation levels among different subgroups of human coronary tissue in the CON, CHD, and SCD groups using pyrophosphate sequencing. The results revealed reduced GAL-8 promoter methylation levels in the SCD group, while the difference between the CHD and CON groups was not statistically significant (P > 0.05). The reduced GAL-8 promoter methylation level was associated with upregulated GAL-8 expression, which led to increased expression of the inflammatory markers TNF-α, IL-1ß, MCP-1, MIP-2, MMP-2, and MMP-9. This enhanced inflammatory response contributed to the accumulation of foam cells, thickening of the intima of human coronary arteries, and increased luminal stenosis, which promoted the occurrence of sudden coronary death. Next, we found that GAL-8 promoter methylation levels in PBMC were consistent with human coronary tissue. The unstable angina group (UAP) had significantly lower GAL-8 promoter methylation levels than stable angina (SAP) and healthy controls (CON) (P < 0.05), and there was a significant correlation between reduced GAL-8 promoter methylation levels and risk factors for coronary heart disease. These findings highlight the association between decreased GAL-8 promoter methylation and the presence of coronary heart disease risk factors. ROC curve analysis suggests that methylation of the GAL 8 promoter region is an independent risk factor for CHD. In conclusion, our study confirmed differential expression of GAL-8, LTF, MUC4D, TMEM9B, MYOM2, and ANK3 genes due to DNA methylation in the SCD group. We also established the consistency of GAL-8 promoter methylation alterations between human coronary tissue and patient peripheral blood monocytes. The decreased methylation level of the GAL-8 promoter may be related to the increased expression of GAL-8 and the coronary risk factors. CONCLUSIONS: Accordingly, we hypothesized that reduced levels of GAL-8 promoter methylation may be an independent risk factor for adverse events in coronary heart disease.
Sujet(s)
Maladie coronarienne , Agranulocytes , Humains , Méthylation de l'ADN/génétique , Maladie coronarienne/diagnostic , Maladie coronarienne/génétique , Maladie coronarienne/épidémiologie , Régions promotrices (génétique)/génétique , Inflammation/génétique , Protéines de transport/génétiqueRÉSUMÉ
In recent years, the incidence of thyroid cancer has been on a significant rise worldwide, and a number of environmental factors have been suspected to be risk factors for thyroid cancer, especially the relationship between iodine intake and thyroid cancer has attracted attention. In this study, we want to assess the relationship between different water iodine exposures and thyroid cancer incidence before and after water alteration in areas with high water iodine in China. Thyroid cancer patients (2009-2020) were enrolled at two hospitals, both in Heze City, Shandong Province, an area with high water iodine levels. According to the criteria of the study, 5826 cases out of 8785 cases were selected for inclusion in the study. Before and after water alteration, the incidence of thyroid cancer was highest in areas with water iodine concentrations of 200-300 µg/L in high iodine areas. In areas where water iodine decreased to adequate iodine levels, there was a strong negative correlation between the decreased level of water iodine and the incidence of thyroid cancer. In addition, in cases with pathology reports, we found that the greater the decrease in water iodine values, the markedly smaller the maximum diameter of the thyroid cancer lesions. Taken together, these findings suggest that we should continue to monitor the incidence of thyroid cancer in areas with high water iodine and continue to optimize population iodine intake to reduce the incidence of thyroid cancer.
Sujet(s)
Iode , Tumeurs de la thyroïde , Humains , Iode/analyse , Eau , Études rétrospectives , Tumeurs de la thyroïde/induit chimiquement , Tumeurs de la thyroïde/épidémiologie , Chine/épidémiologieRÉSUMÉ
To screen strains with antibacterial and antitumor activity, pregnenolone was used as the sole carbon source for screening bacteria from soil. Based on bacteriostatic activity assay, Pseudomonas aeruginosa HBD-12 was found to be effectively inhibiting the growth of Escherichia coli, Bacillus thuringiensis, Penicillium digitatum and Penicillium italicum, and its fermentation broth was separated and purified using column chromatography. Then, structure of the obtained monomeric compounds was analyzed by spectrum analysis, and their antitumor activity was measured using HTRF kinase detection kit. The isolated monomeric compounds 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline had significant antitumor activity. At 20 μg/mL, 1-hydroxy-9,10-phenanthroline and 3-hydroxy-9,10-dihydrophenanthroline inhibited 78.39±2.29% and 60.34±8.35% Aurora kinase A, respectively. Therefore, the secondary metabolites of Pseudomonas aeruginosa HBD-12 have the potential to develop antibacterial and antitumor drugs.
Sujet(s)
Antibactériens/pharmacologie , Tests de sensibilité microbienne , Penicillium , Pseudomonas aeruginosaRÉSUMÉ
<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) on the circadian rhythm and suprachiasmatic nucleus (SCN) epigenetic modification in mice with hepatocellular carcinoma (HCC), and to explore the epigenetics mechanism of EA on circadian rhythm in patients with HCC.</p><p><b>METHODS</b>According to six zeitbeger time (ZT) of ZT0 (7:00), ZT4 (11:00), ZT8 (15:00), ZT12 (19:00), ZT16 (23:00) and ZT20 (3:00), a total of 108 eligible male C57BL/6J mice were divided into a blank group, a model group and an EA group at each ZT, 6 mice each group. Injection of H22 cancer cell suspension was used to establish the HCC model. After 11 days, EA (2 Hz/15 Hz, 0.2 mA) for 10 days was applied at "Ganshu" (BL 18) and "Zhiyang" (GV 9) in the EA group at each ZT, once a day, 15 min a time; the rats in the blank group and model group were treated with immobilization at the same time and under the same conditions. ClockLab (ACT-500) software was used to record the activity rhythm of mice. After 10 days intervention, MATLAB (R2007b) was used to export the circadian rhythm of mice, and the amplitude and peak phase of the mice were analyzed. The high-throughput epigenetics PCRarray array was applied to detect epigenetics-related gene expression in SCN.</p><p><b>RESULTS</b>(1) After modeling, compared with the blank group, the amplitude of activity was decreased and peak phase was delayed in the model group and EA group at each ZT (all <0.05), but the difference of rhythm parameters between the model group and EA group was not significant (all > 0.05). (2) After intervention, compared with the model group, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (both <0.05); the difference of the activity amplitude and peak phase between the EA group and model group at ZT0, ZT4, ZT12, ZT16 and ZT20 was not significant (all >0.05); compared with the ZT0, ZT4, ZT12, ZT16 and ZT20, the amplitude of activity in the EA group at ZT 8 was increased and peak phase was advanced (all <0.05). (3) The results of epigenetic PCRarray array showed that after intervention at ZT 8, compared with the blank group, the expression of 48 epigenetic-related genes in SCN of HCC mice was up-regulated; compared with the model group, the relative expression of 49 epigenetic-related genes in the SCN was down-regulated in the EA group; there were 23 epigenetic-related genes differentially expressed among the three groups.</p><p><b>CONCLUSION</b>EA has benign regulation on circadian rhythm of HCC mice, and achieves the best efficacy at ZT 8. EA at ZT 8 could down-regulate the overexpression of epigenetic-related genes.</p>
RÉSUMÉ
<p><b>OBJECTIVE</b>To explore the possible mechanism of lipid deposition induced by interferon-gamma (IFN-gamma).</p><p><b>METHODS</b>The mouse mesangial cells (MMC) were randomly divided into control group, stimulation group, stimulation + control vector group (sh-HMGB1) and stimulation+ specific sh-vector group (sh-SREBP-1). RT-PCR was used to detect the expression of HMGB1, SREBP-1 and fatty acid synthetase (FAS) mRNA; the protein expression was determined by Western blot.</p><p><b>RESULTS</b>The Oil Red O staining revealed that the mouse mesangial cells showed significant lipid droplet in IFN-gamma group. IFN-gamma up-regulated the expression of HMGB1, SREBP-1, FAS mRNA and protein time-dependently; Transfection of MMC with HMGB1 siRNA resulted in the suppression of SREBP-1, FAS protein levels induced by IFN-gamma, following with decrease of lipid deposition. Stimulation with HMGB1 markedly induced expression of SREBP-1, FAS expression and peaked at 8 h, decreased at 12 h compared with that at 8 h. Sh-SREBP-1 decreased the lipid deposition induced by HMGB1 in MMC.</p><p><b>CONCLUSION</b>IFN-gamma might induce lipid deposition in mouse mesangial cells partly by up-regulating the expression of HMGB1/SREBP-1/FAS.</p>