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Sub-nanoclusters with ultra-small particle sizes are particularly significant to create advanced energy storage materials. Herein, Sn sub-nanoclusters encapsulated in nitrogen-doped multichannel carbon matrix (denoted as Sn-SCs@MCNF) are designed by a facile and controllable route as flexible anode for high-performance potassium ion batteries (PIBs). The uniformly dispersed Sn sub-nanoclusters in multichannel carbon matrix can be precisely identified, which ensure us to clarify the size influence on the electrochemical performance. The sub-nanoscale effect of Sn-SCs@MCNF restrains electrode pulverization and enhances the K+ diffusion kinetics, leading to the superior cycling stability and rate performance. As freestanding anode in PIBs, Sn-SCs@MCNF manifests superior K+ storage properties, such as exceptional cycling stability (331 mAh g-1 after 150 cycles at 100 mA g-1) and rate capability. Especially, the Sn-SCs@MCNF||KFe[Fe(CN)6] full cell demonstrates impressive reversible capacity of 167 mAh g-1 at 0.4 A g-1 even after 200 cycles. Theoretical calculations clarify that the ultrafine Sn sub-nanoclusters are beneficial for electron transfer and contribute to the lower energy barriers of the intermediates, thereby resulting in promising electrochemical performance. Comprehensive investigation for the intrinsic K+ storage process of Sn-SCs@MCNF is revealed by in situ analysis. This work provides vital guidance to design sub-nanoscale functional materials for high-performance energy-storage devices.
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Preferential oxidation of CO (CO-PROX) has tremendous significance in purifying hydrogen for fuel cells to avoid catalyst poisoning by CO molecules. Traditional powder catalysts face numerous challenges, including high pressure drop, aggregation tendency, hotspot formation, poor mass and heat transfer efficiency, and inadequate thermal stability. Accordingly, ceramic monolithic catalysts, known as their excellent thermal stability, high surface area, and superior mass and heat transfer characteristics, are gaining increasing research attention. This review examines recent studies on ceramic monolithic catalysts in CO-PROX, placing emphasis on the regulation of active sites (e.g., precious metals like Pt and Au, and non-precious metals like CuO and CeO2), monolith structures, and coating strategies. In addition, the structure-catalytic performance relationships, as well as the potential and limitations of different ceramic monolithic catalysts in practical application, are discussed. Finally, the challenges of monolithic catalysts and future research prospects in CO-PROX reactions are highlighted.
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The fatal gouty disease caused by goose astrovirus genotype 2 (GAstV-2) still seriously endangers the goose industry in China, causing great economic losses. However, research on its infection mechanism has progressed relatively slowly. VP70 is the structural protein of GAstV-2 and is closely related to virus invasion and replication. To better understand the role of VP70 during GAstV-2 infection, we used immunoprecipitation and mass spectrometry to identify host proteins that interact with VP70. Here, we report that cellular vimentin (VIM) is a host binding partner of VP70. Site-directed mutagenesis showed that amino acid residues 399 to 413 of VP70 interacted with VIM. Using reverse genetics, we found that VP70 mutation disrupts the interaction of VP70 with VIM, which is essential for viral replication. Overexpression of VIM significantly promoted GAstV-2 replication, while knockdown of VIM significantly inhibited GAstV-2 replication. Laser confocal microscopy showed that VP70 protein expression induced the rearrangement of VIM, gradually aggregating from the original uniform grid to the side of the nucleus, and aggregated the originally dispersed GAstV-2 RNA in VIM. This rearrangement was associated with increased VIM phosphorylation caused by GAstV-2. Meanwhile, blocking VIM rearrangement with acrylamide substantially inhibited viral replication. These results indicate that VIM interacts with VP70 and positively regulates GAstV-2 replication, and VIM-VP70 interaction and an intact VIM network are needed for GAstV-2 replication. This study provides a theoretical basis and novel perspective for the further characterization of the pathogenic mechanism of GAstV-2-induced gouty disease in goslings.
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Goose astrovirus (GAstV) has been widespread in China since 2016, causing significant growth inhibition and gout symptoms in goslings and leading to substantial economic losses in the goose industry. To better understand the epidemiological characteristics of GAstV in Guangdong Province, 682 samples were collected from geese with suspected GAstV infection across different regions of Guangdong Province from January 2022 to January 2024. Virus isolation, identification, and genetic evolution analysis were performed. The results showed that all samples were GAstV positive, with 52.64% co-infected with GAstV-1 and GAstV-2, and 42.38% positive for GAstV-2 alone, indicating that GAstV-2 remains the most prevalent subtype. Additionally, three GAstV isolates were identified using molecular detection, immunofluorescence, and transmission electron microscopy on LMH cells or goose embryos. Compared with GDYJ2304 and other reported GAstV-2 strains, the ORF2 region of the GDYJ2210 isolates lacked 3 bases, and the replication ability of GDYJ2210 was significantly higher than that of GDYJ2304. Whole genome sequence alignment and genetic evolution analysis revealed that the GDFS2209 isolate was located in the GAstV-1 branch, with a sequence similarity of 89.70 to 99.00% to GAstV-1 reference strains. The GDYJ2210 and GDYJ2304 isolates were located in the GAstV-2 branch, showing a sequence similarity of 96.80 to 98.90% to GAstV-2 reference strains. These results demonstrated that the GAstV isolates were highly similar to each other despite being prevalent in 5 different regions of Guangdong Province. These findings enhance the understanding of the genetic diversity and evolution of GAstV and may facilitate the development of effective preventive strategies.
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OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.
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BACKGROUND: There is ongoing uncertainty about the effectiveness of various adjuvant treatments for low-grade gliomas (LGGs). Machine learning (ML) models that predict individual treatment effects (ITE) and provide treatment recommendations could help tailor treatments to each patient's needs. OBJECTIVE: We sought to discern the individual suitability of radiotherapy (RT) or chemoradiotherapy (CRT) in LGG patients using ML models. METHODS: Ten ML models, trained to infer ITE in 4,042 LGG patients, were assessed. We compared patients who followed treatment recommendations provided by the models with those who did not. To mitigate the risk of treatment selection bias, we employed inverse probability treatment weighting (IPTW). RESULTS: The Balanced Survival Lasso-Network (BSL) model showed the most significant protective effect among all the models we tested (hazard ratio (HR): 0.52, 95% CI, 0.41-0.64; IPTW-adjusted HR: 0.58, 95% CI, 0.45-0.74; the difference in restricted mean survival time (DRMST): 9.11, 95% CI, 6.19-12.03; IPTW-adjusted DRMST: 9.17, 95% CI, 6.30-11.83). CRT presented a protective effect in the 'recommend for CRT' group (IPTW-adjusted HR: 0.60, 95% CI, 0.39-0.93) yet presented an adverse effect in the 'recommend for RT' group (IPTW-adjusted HR: 1.64, 95% CI, 1.19-2.25). Moreover, the models predict that younger patients and patients with overlapping lesions or tumors crossing the midline are better suited for CRT (HR: 0.62, 95% CI, 0.42-0.91; IPTW-adjusted HR: 0.59, 95% CI, 0.36-0.97). CONCLUSION: Our findings underscore the potential of the BSL model in guiding the choice of adjuvant treatment for LGGs patients, potentially improving survival time. This study emphasizes the importance of ML in customizing patient care, understanding the nuances of treatment selection, and advancing personalized medicine.
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Neoplasias Encefálicas , Quimiorradioterapia , Glioma , Aprendizado de Máquina , Humanos , Glioma/terapia , Glioma/radioterapia , Glioma/patologia , Glioma/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Quimiorradioterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Gradação de Tumores , Idoso , Resultado do TratamentoRESUMO
The rational design of carbon-supported transition metal single-atom catalysts necessitates precise atomic positioning within the precursor. However, structural collapse during pyrolysis can occlude single atoms, posing significant challenges in controlling both their utilization and coordination environment. Herein, we present a surface atom adsorption-flash heating (FH) strategy, which ensures that the pre-designed carbon nanofiber structure remains intact during heating, preventing unforeseen collapse effects and enabling the formation of metal atoms in nano-environments with either tetra-nitrogen or penta-nitrogen coordination at different flash heating temperatures. Theoretical calculations and in situ Raman spectroscopy reveal that penta-nitrogen coordinated cobalt atoms (Co-N5) promote a lower energy pathway for oxygen reduction and oxygen evolution reactions compared to the commonly formed Co-N4 sites. This strategy ensures that Co-N5 sites are fully exposed on the surface, achieving exceptionally high atomic utilization. The turnover frequency (65.33 s-1) is 47.4 times higher than that of 20% Pt/C under alkaline conditions. The porous, flexible carbon nanofibers significantly enhance zinc-air battery performance, with a high peak power density (273.8 mW cm-2), large specific capacity (784.2 mA h g-1), and long-term cycling stability over 600 h. Additionally, the flexible fiber-shaped zinc-air battery can power wearable devices, demonstrating significant potential in flexible electronics applications.
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The poor durability of Ru-based catalysts limits the practical application in proton exchange membrane water electrolysis (PEMWE). Here, we report that the asymmetric active units in Ru1-xMxO2 (M = Sb, In, and Sn) binary solid solution oxides are constructed by introducing acid-resistant p-block metal sites, breaking the activity and stability limitations of RuO2 in acidic oxygen evolution reaction (OER). Constructing highly asymmetric Ru-O-Sb units with a strong electron delocalization effect significantly shortens the spatial distance between Ru and Sb sites, improving the bonding strength of the overall structure. The unique two-electron redox couples at Sb sites in asymmetric active units trigger additional chemical steps at different OER stages, facilitating continuous proton transfer. The optimized Ru0.8Sb0.2O2 solid solution requires a superlow overpotential of 160 mV at 10 mA cm-2 and a record-breaking stability of 1100 h in an acidic electrolyte. Notably, the scale-prepared Ru0.8Sb0.2O2 achieves efficient PEMWE performance under industrial conditions. General mechanism analysis shows that the enhanced proton transport in the asymmetric Ru-O-M unit provides a new working pathway for acidic OER, breaking the scaling relationship without sacrificing stability.
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There is no evidence on the associations between persistent organic pollutants (POPs) and the incidence of chronic kidney disease (CKD) in the Chinese rural population. We aimed to investigate the individual and mixed effects of 22 POPs on the prevalence and incidence of CKD, and the joint effects of POPs and abnormal glucose metabolism as well as the modification effects of healthy lifestyle on these associations. A total of 2775 subjects, including 925 subjects with normal plasma glucose (NPG) and 925 subjects with prediabetes (PDM) and type 2 diabetes mellitus (T2DM), were enrolled from the Henan Rural Cohort Study. Logistic regression and quantile g-computation were performed to assess the individual and mixed effects of POPs on the risk of CKD. Joint effects of POPs and abnormal glucose metabolism status, as well as the modification effects of lifestyle on CKD were assessed. After 3-year follow-up, an increment of ln-o,p'-DDT was related to an elevated risk of CKD prevalence. Positive associations of p,p'-DDE and ß-BHC with CKD incidence were observed (P < 0.05). In addition, participants with high levels of ∑POPs were associated elevated incidence risk of CKD (OR: 1.217, 95%CI: 1.008-1.469). One quartile increase in POPs mixture was associated with the increased incidence of CKD among T2DM patients (P < 0.05). Further, a higher risk of CKD was observed among PDM and T2DM patients with high levels of o,p'-DDT, p,p'-DDE, ß-BHC, and ∑POPs than NPG subjects with low levels of pollutants. In addition, interactive effects of ∑POPs and lifestyle score on CKD incidence were found. Individual and mixed exposure to POPs increased the prevalence and incidence of CKD, and glucose metabolic status exacerbated the risk of CKD resulting from such exposures. Further, the modifying effects of lifestyle were observed, highlighting the importance of precision prevention for high-risk CKD population and healthy lifestyle intervention measures.
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Objective: The objective of this study is to examine the risk factors associated with apnea in hospitalized patients diagnosed with bronchiolitis and to develop a nomogram prediction model for the early identification of patients who are at risk of developing apnea. Methods: The clinical data of patients diagnosed with acute bronchiolitis and hospitalized at the Children's Hospital of Nanjing Medical University between February 2018 and May 2021 were retrospectively analyzed. LASSO regression and logistic regression analysis were used to determine the risk factors for apnea in these patients. A nomogram was constructed based on variables selected through multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve and calibration curve were used to assess the accuracy and discriminative ability of the nomogram model, and decision curve analysis (DCA) was performed to evaluate the model's performance and clinical effectiveness. Results: A retrospective analysis was conducted on 613 children hospitalized with bronchiolitis, among whom 53 (8.6%) experienced apnea. The results of Lasso regression and Logistic regression analyses showed that underlying diseases, feeding difficulties, tachypnea, WBC count, and lung consolidation were independent risk factors for apnea. A nomogram prediction model was constructed based on the five predictors mentioned above. After internal validation, the nomogram model demonstrated an AUC of 0.969 (95% CI 0.951-0.987), indicating strong predictive performance for apnea in bronchiolitis. Calibration curve analysis confirmed that the nomogram prediction model had good calibration, and the clinical decision curve analysis (DCA) indicated that the nomogram was clinically useful in estimating the net benefit to patients. Conclusion: In this study, a nomogram model was developed to predict the risk of apnea in hospitalized children with bronchiolitis. The model showed good predictive performance and clinical applicability, allowing for timely identification and intensified monitoring and treatment of high-risk patients to improve overall clinical prognosis.
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Biological control is a promising approach to enhance pathogen and pest control to ensure high productivity in cash crop production. Therefore, PGPR biofertilizers are very suitable for application in the cultivation of tea plants (Camellia sinensis) and tobacco, but it is rarely reported so far. In this study, production of a consortium of three strains of PGPR were applied to tobacco and tea plants. The results demonstrated that plants treated with PGPR exhibited enhanced resistance against the bacterial pathogen Pseudomonas syringae (PstDC3000). The significant effect in improving the plant's ability to resist pathogen invasion was verified through measurements of oxygen activity, bacterial colony counts, and expression levels of resistance-related genes (NPR1, PR1, JAZ1, POD etc.). Moreover, the application of PGPR in the tea plantation showed significantly reduced population occurrences of tea green leafhoppers (Empoasca onukii Matsuda), tea thrips (Thysanoptera:Thripidae), Aleurocanthus spiniferus (Quaintanca) and alleviated anthracnose disease in tea seedlings. Therefore, PGPR biofertilizers may serve as a viable biological control method to improve tobacco and tea plant yield and quality. Our findings revealed part of the mechanism by which PGPR helped improve plant biostresses resistance, enabling better application in agricultural production.
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Nicotiana , Controle Biológico de Vetores , Doenças das Plantas , Pseudomonas syringae , Animais , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Nicotiana/microbiologia , Pseudomonas syringae/fisiologia , Controle Biológico de Vetores/métodos , Camellia sinensis/microbiologia , Camellia sinensis/crescimento & desenvolvimento , Insetos/microbiologia , Tisanópteros/microbiologia , Resistência à Doença , Desenvolvimento Vegetal , Agentes de Controle Biológico , Hemípteros/microbiologiaAssuntos
Erros Inatos do Metabolismo dos Carboidratos , Duplicação Gênica , Transportador de Glucose Tipo 1 , Humanos , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/deficiência , Erros Inatos do Metabolismo dos Carboidratos/genética , Masculino , Mutação , Feminino , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/deficiênciaRESUMO
BACKGROUND: Hemophilia A (HA) is an X-linked recessive genetic disorder caused by pathogenic variations of the factor VIII -encoding gene, F8 gene. Due to the large size and diverse types of variations in the F8 gene, causative mutations in F8 cannot be simultaneously detected in one step by traditional molecular analysis, and genetic molecular diagnosis and prenatal screening of HA still face significant difficulties and challenges in clinical practice. Therefore, we aimed to develop and validate an efficient, accurate, and time-saving method for the genetic detection of HA. METHODS: A comprehensive analysis of hemophilia A (CAHEA) method based on long-range PCR and long-read sequencing (LRS) was used to detect F8 gene mutations in 14 clinical HA samples. The LRS results were compared with those of the conventional methods to evaluate the accuracy and sensitivity of the proposed approach. RESULTS: The CAHEA method successfully identified 14 F8 variants in all probands, including 3 small insertion deletions, 4 single nucleotide variants, and 7 intron 22 inversions in a "one-step" manner, of which 2 small deletions have not been reported previously. Moreover, this method provided an opportunity to analyze the mechanism of rearrangement and the pathogenicity of F8 variants. The LRS results were validated and found to be in 100% agreement with those obtained using the conventional method. CONCLUSION: Our proposed LRS-based F8 gene detection method is an accurate and reproducible genetic screening and diagnostic method with significant clinical value. It provides efficient, comprehensive, and accurate genetic screening and diagnostic services for individuals at high risk of HA as well as for premarital and prenatal populations.
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Fator VIII , Hemofilia A , Hemofilia A/genética , Hemofilia A/diagnóstico , Humanos , Fator VIII/genética , Variação Genética , Mutação , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
Although starch has been intensively studied as a raw material for 3D printing, the relationship between several important process parameters in the preparation of starch gels and the printing results is unclear. In this study, the relationship between different processing conditions and the gel printing performance of corn starch was evaluated by printing tests, rheological tests and low-field nuclear magnetic resonance (LF-NMR) tests, and a back-propagation artificial neural network (BP-ANN) model for predicting gel printing performance was developed. The results revealed that starch gels exhibited favorable printing performance when the gelatinization temperature ranged from 75 °C to 85 °C, and the starch content was maintained between 15 % and 20 %. The R2adj of the BP-ANN models were all reached 0.894, which indicated good predictive ability. The results of the study not only provide theoretical support for the application of corn starch gels in 3D food printing, but also present a novel approach for predicting the printing performance of related materials. This method contributes to the optimization of printing parameters, thereby enhancing printing efficiency and quality.
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Redes Neurais de Computação , Impressão Tridimensional , Amido , Zea mays , Amido/química , Zea mays/química , Tinta , Reologia , Géis/química , TemperaturaRESUMO
Jinhu groupers, the hybrid offspring of tiger groupers (Epinephelus fuscoguttatus) and potato groupers (Epinephelus tukula), have excellent heterosis in fast growth and strong stress resistance. However, compared with the maternal tiger grouper, Jinhu groupers show delayed gonadal development. To explore the interspecific difference in gonadal development, we compared the transcriptomes of brain, pituitary, and gonadal tissues between Jinhu groupers and tiger groupers at 24-months old. In total, 3034 differentially expressed genes (DEGs) were obtained. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that the osteoclast differentiation, oocyte meiosis, and ovarian steroidogenesis may be involved in the difference in gonadal development. Trend analysis showed that the DEGs were mainly related to signal transduction and cell growth and death. Additionally, differences in expression levels of nr4a1, pgr, dmrta2, tbx19, and cyp19a1 may be related to gonadal retardation in Jinhu groupers. A weighted gene co-expression network analysis revealed three modules (i.e., saddlebrown, paleturquoise, and greenyellow) that were significantly related to gonadal development in the brain, pituitary, and gonadal tissues, respectively, of Jinhu groupers and tiger groupers. Network diagrams of the target modules were constructed and the respective hub genes were determined (i.e., cdh6, col18a1, and hat1). This study provides additional insight into the molecular mechanism underlying ovarian stunting in grouper hybrids.
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Bass , Transcriptoma , Animais , Feminino , Transcriptoma/genética , Bass/genética , Bass/crescimento & desenvolvimento , Bass/metabolismo , Masculino , Perfilação da Expressão Gênica/métodos , Sistema Hipotálamo-Hipofisário/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Gônadas/metabolismo , Gônadas/crescimento & desenvolvimento , Hipófise/metabolismo , Ovário/metabolismo , Ovário/crescimento & desenvolvimento , Eixo Hipotalâmico-Hipofisário-GonadalRESUMO
BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.
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Neoplasias Ósseas , Condrossarcoma , Imageamento por Ressonância Magnética , Gradação de Tumores , Nomogramas , Humanos , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Adulto , Idoso , Curva ROC , Adulto Jovem , RadiômicaRESUMO
Myocardial injury and cardiovascular dysfunction are the most common complications of sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide-induced sepsis and its related signalling pathways. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK-MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis-related proteins including: Nod-like receptor protein 3 (NLRP3), Caspase 1, Apoptosis-associated speck-like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase-1 (HO-1) because Nrf2-knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3-mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS-induced myocardial injury by suppressing NLRP3-mediated pyroptosis via the Nrf2/HO-1 signalling pathway in vivo and in vitro.
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Heme Oxigenase-1 , Inflamação , Lipopolissacarídeos , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Oxicodona , Piroptose , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Piroptose/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Camundongos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Heme Oxigenase-1/metabolismo , Oxicodona/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Masculino , Linhagem Celular , Ratos , Oxirredução/efeitos dos fármacos , Camundongos Knockout , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.
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Fluorescence molecular tomography (FMT) serves as a noninvasive modality for visualizing volumetric fluorescence distribution within biological tissues, thereby proving to be an invaluable imaging tool for preclinical animal studies. The conventional FMT relies upon a point-by-point raster scan strategy, enhancing the dataset for subsequent reconstruction but concurrently elongating the data acquisition process. The resultant diminished temporal resolution has persistently posed a bottleneck, constraining its utility in dynamic imaging studies. We introduce a novel system capable of simultaneous FMT and surface extraction, which is attributed to the implementation of a rapid line scanning approach and dual-camera detection. The system performance was characterized through phantom experiments, while the influence of scanning line density on reconstruction outcomes has been systematically investigated via both simulation and experiments. In a proof-of-concept study, our approach successfully captures a moving fluorescence bolus in three dimensions with an elevated frame rate of approximately 2.5 seconds per frame, employing an optimized scan interval of 5 mm. The notable enhancement in the spatio-temporal resolution of FMT holds the potential to broaden its applications in dynamic imaging tasks, such as surgical navigation.
Assuntos
Imageamento Tridimensional , Imagens de Fantasmas , Imageamento Tridimensional/métodos , Fluorescência , Animais , Imagem Óptica/métodos , LuzRESUMO
Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer cells can serve as a target for imaging and radioligand therapy (RLT). Previously, [68Ga]Ga-P16-093, containing a Ga(III) chelator, N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), displayed excellent PSMA-targeting properties and showed a high tumor uptake and retention useful for diagnosis in prostate cancer patients. Recently, [177Lu]Lu-PSMA-617 has been approved by the U.S. food and drug administration (FDA) for the treatment of prostate cancer patients. Derivatives of PSMA-093 using AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), as the chelator, were designed as alternative agents forming complexes with both diagnostic and therapeutic radiometals, such as gallium-68 (log K = 22.18) or lutetium-177 (log K = 21.85). The aim of this study is to evaluate AAZTA-Gly-O-(methylcarboxy)-Tyr-Phe-Lys-NH-CO-NH-Glu (designated as AZ-093, 1) leading to a gallium-68/lutetium-177 theranostic pair as potential PSMA targeting agents. Synthesis of the desired precursor, AZ-093, 1, was effectively accomplished. Labeling with either [68Ga]GaCl3 or [177Lu]LuCl3 in a sodium acetate buffer solution (pH 4-5) at 50 °C in 5 to 15 min produced either [68Ga]Ga-1 or [177Lu]Lu-1 with high yields and excellent radiochemical purities. Results of in vitro binding studies, cell uptake, and retention (using PSMA-positive prostate carcinoma cells line, 22Rv1-FOLH1-oe) were comparable to that of [68Ga]Ga-P16-093 and [177Lu]Lu-PSMA-617, respectively. Specific cellular uptake was determined with or without the competitive blocking agent (2 µM of "cold" PSMA-11). Cellular binding and internalization showed a time-dependent increase over 2 h at 37 °C in the PSMA-positive cells. The cell uptakes were completely blocked by the "cold" PSMA-11 suggesting that they are competing for the same PSMA binding sites. In the mouse model with implanted PSMA-positive tumor cells, both [68Ga]Ga-1 and [177Lu]Lu-1 displayed excellent uptake and retention in the tumor. Results indicate that [68Ga]Ga/[177Lu]Lu-1 (68Ga]Ga/[177Lu]Lu-AZ-093) is potentially useful as PSMA-targeting agent for both diagnosis and radiotherapy of prostate cancer.