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BACKGROUND: Interventional endoscopic ultrasound is clinically used for the treatment of isolated gastric varices (IGVs) owing to its precise visualization. CASE SUMMARY: A 39-year-old man was diagnosed with a large IGV during a routine physical examination. Endoscopic ultrasonography showed gastric varices entwined with an artery, which greatly increased the difficulty of treatment. We successfully treated the patient with endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection. CONCLUSION: Endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection was safe and effective for the treatment of an IGV entwined with an artery.
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Despite global efforts to manage water eutrophication, the continual release of ammonia nitrogen from sediments maintains the eutrophic state of water bodies, presenting serious challenges to the management. In order to find an efficient method for sediment remediation, the experiment of using signal molecules to enhance the adhesion of microorganisms on zeolite was carried out. Five different zeolitic ammonium adsorptions were examined using two different signal molecules, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) and N-(ß-ketocaproyl)-DL-homoserine lactone (C6), to enhance microbial attachment on two types of zeolites. The results showed that the modified microbial attached Z1 zeolite reinforced with signal molecule C6 had the best effect. The effect was better in the case of high ammonium adsorption, and the TN removal could reach 7.99 mg·L-1 with an inhibition rate of 90.08%. The ammonia nitrogen removal reached 4.75 mg·L-1 with an inhibition rate of 87.64%, and the ammonia nitrogen and total nitrogen of the overlying water reached the surface III water quality standard. In addition, the addition of the signal molecule increased the zeta potential on the surface of the bacterial colloid. In addition, the amount of protein I in the dissolved organic matter (DOM) fraction increased, improving microbial adhesion ability and facilitating their attachment to the zeolite surface. The signal molecule C6 could increase the zeta potential of microbial surface and promote the production of protein I, thus strengthening the attachment of zeolite biofilm and improving the water quality.
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Sulfonated biochar (SBC), as a functional carbon-based material, has attracted widespread attention due to its excellent adsorption properties. The composition of biochar-derived organic matter (B-DOM) is a key factor influencing the migration and transformation of soil elements and pollutants. However, molecular characteristics of sulfonated biochar-derived organic matter (SBC-DOM) are still unclear. In this study, the molecular composition of derived organic matter (DOM) from SBC prepared via one-step carbonization-sulfonation techniques was investigated by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and then compared with those of DOMs from rice husk (RH), pyrochar (PYC), and hydrochar (HYC). The results show that the CHOS- and CHONS-containing formulae are predominant in SBC-DOM, accounting for 85% of the total molecular formula number, while DOMs from RH, PYC, and HYC are dominated by CHO-containing formulae. Compared to PYC-DOM and HYC-DOM, SBC-DOM has more unsaturated aliphatic compounds, which make it more labile and easily biodegraded. Additionally, SBC-DOM has higher O/C, (N + O)/C ratios and sulfur-containing compounds. These findings provide a theoretical basis for further research on the application of sulfonated biochar in soil improvement and remediation.
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RATIONALE: High-resolution mass spectrometry (HRMS) combined with electrospray ionization (ESI) has been the most useful technique for molecular characterization of dissolved organic matter (DOM) derived from diverse sources. However, the comprehensive detection of DOM composition was hindered by ionization suppression observed in ESI sources. HRMS coupled with liquid chromatography (LC) is a potential tool for comprehensive molecular characterization of DOM. METHODS: The Suwannee River fulvic acids (SRFAs) and two DOM samples from seawater and refinery wastewater extracted by solid phase extraction (SPE) were analyzed by LC-Orbitrap MS coupled with ESI. The mobile phases, solvent composition, and gradient in the LC-Orbitrap MS analysis were optimized. RESULTS: The number of detected molecular formulae of SRFAs by online LC-Orbitrap MS was significantly increased by approximately 40% compared to direct injection. These additional detected compounds are mainly protein and lignin-like compounds, with a low O/C ratio and high H/C ratio. For the SRFAs, the relative standard deviations (%) of reproducibility are 5.51, 2.33, 7.97, and 1.80 for average O/C, H/C, double bond equivalent, and modified aromaticity index, respectively. CONCLUSIONS: This study proposed a simple and rapid method based on LC-Orbitrap MS for an in-depth analysis of the molecular composition of DOM, achieving a remarkable analysis time of only 5 min per sample. The rapid method provides a dependable and efficient approach for the molecular characterization of DOM, thereby advancing our comprehension and investigation of DOM across diverse ecosystems.
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Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.
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Dissolved organic matter (DOM), the most reactive fraction of forest soil organic matter, is increasingly impacted by wildfires worldwide. However, few studies have quantified the temporal changes in soil DOM quantity and quality after fire. Here, soil samples were collected after the Qipan Mountain Fire (3-36 months) from pairs of burned and unburned sites. DOM contents and characteristics were analyzed using carbon quantification and various spectroscopic and spectrometric techniques. Compared with the unburned sites, burned sites showed higher contents of bulk DOM and most DOM components 3 months after the fire but lower contents of them 6-36 months after the fire. During the sharp drop of DOM from 3 to 6 months after the fire, carboxyl-rich alicyclic molecule-like and highly unsaturated compounds had greater losses than condensed aromatics. Notably, the burned sites had consistently higher abundances of oxygen-poor dissolved black nitrogen and fluorescent DOM 3-36 months after the fire, particularly the abundance of pyrogenic C2 (excitation/emission maxima of <250/â¼400 nm) that increased by 150% before gradually declining. This study advances the understanding of temporal variations in the effects of fire on different soil DOM components, which is crucial for future postfire environmental management.
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Incendios , Suelo , Suelo/química , China , Incendios Forestales , BosquesRESUMEN
Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.
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BACKGROUND: Talent transfer (TT) program is an appropriate approach to address the talent gap evident in specific sports activities, while little is known about the injury characteristics of snowboarding athletes involved in the TT program. OBJECTIVE: To determine the epidemiology of injuries among snowboarders involved in the TT program. METHODS: A total of 244 athletes who were not previously engaged in winter sports were selected for training in snowboarding that lasted for 109 days. The injuries and at-risk exposures (A-Es) data were recorded by physicians. Injury rates (IRs), incidence rate ratios (IRRs), and injury proportion ratios (IPRs) were calculated and compared by sex and age groups. RESULTS: The overall and time loss (TL) IR were 32.4/1000 A-Es and 12.2/1000 A-Es respectively. The overall and non-time loss (NTL) IRR were higher for female athletes than for male athletes. Additionally, the overall IRR and TL-IRR for female athletes were higher in those athletes who aged ≤15 years old. Over 93% of TL injuries resulted in participation restriction time of ≤7 days (male athletes, 93.94%; female athletes, 94.10%). Trunk (28.43%), knee joints (21.33%), and hand/wrist (16.53%) were found as the common sites of injury in both female and male athletes. The most frequent type of injury was contusion (male athletes: 53.00%, female athletes: 59.10%) resulted from ground/apparatus contact (male athletes: 75.10%, female athletes: 75.20%). CONCLUSION: The risk injury among snowboarding athletes involved in the TT program during the first snow season training was found noticeable, especially for younger female athletes. The high incidence of ground/apparatus contact-related injuries suggested the necessity of specifically designed training programs and braces for snowboarding athletes involved in the TT program.
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Atletas , Traumatismos en Atletas , Esquí , Humanos , Femenino , Masculino , Estudios Prospectivos , Traumatismos en Atletas/epidemiología , Adolescente , Adulto , Esquí/lesiones , Adulto Joven , Incidencia , Factores de RiesgoRESUMEN
BACKGROUND: The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. METHODS: Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. RESULTS: A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36-62.65 months). In the training cohort of 1425 patients, through Lasso regression cross-validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5-, and 10-year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723-8.397; log-rank p < 0.001; validation cohort: HR, 8.429; 95% CI, 6.180-11.497; log-rank p < 0.001). CONCLUSION: The prognostic model based on the nutritional indexes of pan-cancer can divide patients into different survival risk groups and performed well in the validation cohort.
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Neoplasias , Nomogramas , Evaluación Nutricional , Estado Nutricional , Humanos , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Neoplasias/mortalidad , Anciano , Modelos de Riesgos Proporcionales , Estudios de Cohortes , Estudios Retrospectivos , Adulto , Tasa de SupervivenciaRESUMEN
Shanxi Province holds an important strategic position in the overall ecological pattern of the Yellow River Basin. To investigate the changes of the ecological environment in the Shanxi section of the Yellow River Basin from 2000 to 2020, we selected MODIS remote sensing image data to determine the remote sensing ecological index (RSEI) based on the principal component analysis of greenness, humidity, dryness, and heat. Then, we analyzed the spatial and temporal variations of ecological quality in this region to explore the influencing factors. We further used the CA-Markov model to simulate and predict the ecological environment under different development scenarios in the Shanxi section of the Yellow River Basin in 2030. The results showed that RSEI had good applicability in the Shanxi section of the Yellow River Basin which could be used to monitor and evaluate the spatiotemporal variations in its ecological environment. From 2000 to 2020, the Shanxi section of the Yellow River Basin was dominated by low quality habitat areas, in which the ecological environment quality continued to improve from 2000 to 2010 and decreased from 2010 to 2020. The high quality habitat areas mainly located on the mountainous areas with superior natural conditions and rich biodiversity, while the low ecological quality areas were mainly in the Taiyuan Basin and the northern part of the study area, where the mining industry developed well. Climate factors were negatively correlated with ecological environment quality in the northern and central parts of the study area, and positively correlated with that in the mountainous area. Under all three development scenarios, the area of cultivated land, forest, water and construction land increased in 2030 compared to that in 2020. Compared to the natural development scenario and the cultivated land protection scenario, the ecological constraint scenario with RSEI as the limiting factor had the highest area of new forest and the lowest expansion rate of cultivated land and construction land. The results would provide a reference for land space planning and ecological environment protection in the Shanxi section of the Yellow River Basin.
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Conservación de los Recursos Naturales , Ecosistema , Monitoreo del Ambiente , Tecnología de Sensores Remotos , Ríos , China , Monitoreo del Ambiente/métodos , Imágenes Satelitales , EcologíaRESUMEN
BACKGROUND: Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. METHODS: Forty patients with melancholic major depressive disorder (MDD), forty patients with non-melancholic MDD, and fifty healthy controls participated in the social incentive delay (SID) tasks with event-related potential (ERP) recording. We measured one anticipatory ERP(cue-N2) and two consummatory ERPs (FRN, fb-P3). Furthermore, we examined correlation between FRN and consummatory anhedonia. RESULTS: Melancholic MDD patients showed less anticipation of social rewards (cue-N2). Concurrently, melancholic individuals demonstrated diminished reception of social rewards, as evidenced by reduced amplitudes of FRN. Notably, the group x condition interaction effect on FRN was significant (F (2, 127) = 4.15, p = 0.018, η2ρ = 0.061). Melancholic MDD patients had similar neural responses to both gain and neutral feedback (blunted reward positivity), whereas non-melancholic MDD patients (t (39) = 3.09, p = 0.004) and healthy participants (t (49) = 5.25, p < 0.001) had smaller FRN amplitudes when receiving gain feedback relative to neutral feedback. In addition, there was a significant correlation between FRN and consummatory anhedonia in MDD patients. CONCLUSIONS: Our findings indicated that individuals with melancholic MDD exhibit attenuated neural responses to both anticipated and consumed social rewards. This suggests that aberrant processing of social rewards could serve as a potential biomarker for melancholic MDD.
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Anhedonia , Trastorno Depresivo Mayor , Electroencefalografía , Potenciales Evocados , Recompensa , Humanos , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Masculino , Femenino , Adulto , Potenciales Evocados/fisiología , Anhedonia/fisiología , Persona de Mediana Edad , Motivación/fisiología , Anticipación Psicológica/fisiología , Conducta Social , Señales (Psicología) , Adulto Joven , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. METHODS: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. RESULTS: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. CONCLUSIONS: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.
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Neoplasias Encefálicas , Glioma , Proteínas Proto-Oncogénicas c-met , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Humanos , Glioma/patología , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/terapia , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Ratones , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Benzamidas/farmacología , Benzamidas/uso terapéutico , Línea Celular Tumoral , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Femenino , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Crizotinib/farmacología , Crizotinib/uso terapéutico , Modelos Animales de Enfermedad , Niño , Clasificación del Tumor , Anilidas/farmacología , Imidazoles , TriazinasRESUMEN
BACKGROUND: -Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient. METHODS AND RESULTS: -A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84-1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60-1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083). CONCLUSIONS: -Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings.
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Disfunción Eréctil , Encuestas Nutricionales , Ácido Úrico , Humanos , Masculino , Disfunción Eréctil/epidemiología , Disfunción Eréctil/sangre , Ácido Úrico/sangre , Estados Unidos/epidemiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Prevalencia , AncianoRESUMEN
The bioavailable diverse dissolved organic matter (DOM) present in glacial meltwater significantly contributes to downstream carbon cycling in mountainous regions. However, the comprehension of molecular-level characteristics of riverine DOM, from tributary to downstream and their fate in glacier-fed desert rivers remains limited. Herein, we employed spectroscopic and high-resolution mass spectrometry techniques to study both optical and molecular-level characteristics of DOM in the Tarim River catchment, northwest China. The results revealed that the DOC values in the downstream were higher than those in the tributaries, yet they remained comparable to those found in other glacier-fed streams worldwide. Five distinct components were identified using EEM-PARAFAC analysis in both tributary and downstream samples. The dominance of three protein-like components in tributary samples, contrasting with a higher presence of humic-like components in downstream samples, which implied that the dilution and alterations of the glacier DOM signature and overprinting with terrestrial-derived DOM. Molecular composition revealed that thousands of compounds with higher molecular weight and increased aromaticity were transformed, generated and introduced from terrestrial inputs during downstream transportation. The twofold rise in polycyclic aromatic and polyphenolic compounds observed downstream compared to tributaries indicated a greater influx of terrestrial organic matter introduced into the downstream during water transportation. The study suggests that the glacier-sourced DOM experienced minimal photodegradations, with limited influence from human activities, while also being shaped by terrestrial inputs during its transit in the alpine-arid region. This unique scenario offers valuable insights into comprehending the fate of DOM originating from glacial meltwater in arid mountainous regions.
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Cubierta de Hielo , Ríos , China , Ríos/química , Cubierta de Hielo/química , Monitoreo del Ambiente/métodos , Compuestos Orgánicos/análisis , Contaminantes Químicos del Agua/análisis , Sustancias Húmicas/análisis , Espectrometría de Masas , Clima DesérticoRESUMEN
Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.
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Ferroptosis , Trasplante de Corazón , Animales , Ratas , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Masculino , Donantes de Tejidos , Hipotermia Inducida , Envejecimiento/metabolismo , Envejecimiento/genéticaRESUMEN
Targeting NLRP3 inflammasome with inhibitors is a novel strategy for NLRP3-driven diseases. Herein, hit compound 5 possessing an attractive skeleton was identified from our in-house database of oridonin, and then a potential lead compound 32 was obtained by optimization of 5, displaying two-digit nanomolar inhibition on NLRP3. Moreover, compound 32 showed enhanced safety index (SI) relative to oridonin (IC50 = 77.2 vs 780.4 nM, SI = 40.5 vs 8.5) and functioned through blocking ASC oligomerization and interaction of NLRP3-ASC/NEK7, thereby suppressing NLRP3 inflammasome assembly and activation. Furthermore, diverse agonists-induced activations of NLRP3 could be impeded by compound 32 without altering NLRC4 or AIM2 inflammasome. Crucially, compound 32 possessed tolerable pharmaceutical properties and significant anti-inflammatory activity in MSU-induced gouty arthritis model. Therefore, this work enriched the SAR of NLRP3 inflammasome inhibitors and provided a potential candidate for the treatment of NLRP3-associated diseases.
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Antiinflamatorios , Diterpenos de Tipo Kaurano , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/uso terapéutico , Diterpenos de Tipo Kaurano/síntesis química , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Animales , Humanos , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/síntesis química , Relación Estructura-Actividad , Masculino , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/síntesis química , Ratones Endogámicos C57BL , Quinasas Relacionadas con NIMA/antagonistas & inhibidores , Quinasas Relacionadas con NIMA/metabolismoRESUMEN
BACKGROUND: The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations. AIM: To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature. RESULTS: Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14). CONCLUSION: KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations.
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Heavy metals can impact the structure and function of coastal sediment. The dissolved organic matter (DOM) pool plays an important role in determining both the heavy metal toxicity and microbial community composition in coastal sediments. However, how heavy metals affect the interactions between microbial communities and DOM remains unclear. Here, we investigated the influence of heavy metals on the microbial community structure (including bacteria and archaea) and DOM composition in surface sediments of Beibu Gulf, China. Our results revealed firstly that chromium, zinc, cadmium, and lead were the heavy metals contributing to pollution in our studied area. Furthermore, the DOM chemical composition was distinctly different in the contaminated area from the uncontaminated area, characterized by a higher average O/C ratio and increased prevalence of carboxyl-rich alicyclic molecules (CRAM) and highly unsaturated compounds (HUC). This indicates that DOM in the contaminated area was more recalcitrant compared to the uncontaminated area. Except for differences in archaeal diversity between the two areas, there were no significant variations observed in the structure of archaea and bacteria, as well as the diversity of bacteria, across the two areas. Nevertheless, our co-occurrence network analysis revealed that the B2M28 and Euryarchaeota, dominating bacterial and archaeal groups in the contaminated area were strongly related to CRAM. The network analysis also unveiled correlations between active bacteria and elevated proportions of nitrogen-containing DOM molecules. In contrast, the archaea-DOM network exhibited strong associations with nitrogen- and sulfur-containing molecules. Collectively, these findings suggest that heavy metals indeed influence the interaction between microbial communities and DOM, potentially affecting the accumulation of recalcitrant compounds in coastal sediments.
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Archaea , Bacterias , Sedimentos Geológicos , Metales Pesados , Microbiota , Contaminantes Químicos del Agua , Metales Pesados/análisis , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiología , Microbiota/efectos de los fármacos , China , Archaea/efectos de los fármacos , Bacterias/efectos de los fármacos , Bacterias/clasificación , Contaminantes Químicos del Agua/análisis , Monitoreo del AmbienteRESUMEN
Electrochemical C-H mono/multi-bromination regulation of N-sulfonylanilines on the cost-effective CF electrode is described. This reaction proceeds smoothly under mild conditions with a broad substrate scope, affording diverse mono/multi-brominated anilines in moderate to good yields. Mechanism study reveals that this transformation involves anodic oxidation, aromatic electrophilic substitution, and deprotonation. Preliminary electroactive molecule screening results in its prospective application in electroactive MBs for electrochemical biosensors.