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Deoxynivalenol (DON) contamination in food products significantly threatens human health, necessitating a reliable and sensitive detection method. This study aims to develop a simple, low-cost, and effective electrochemical immunoassay method for detecting DON based on the nickeliron bimetallic Prussian blue analog (NiFe PBA). The NiFe PBA nanozymes with high peroxidase-like activity were synthesized using an environmentally friendly chemical precipitation method. In the presence of hydrogen peroxide (H2O2), the current change of thionine oxidation initiated by NiFe PBA nanozymes can be exploited to diagnose DON. Under optimal conditions, the proposed method achieved quantitative detection of DON in the range of 10-107 pg mL-1 with a detection limit of 4.5 pg mL-1 (S/N = 3), demonstrating excellent selectivity, reproducibility, and stability. In addition, the DON immunosensor provides satisfactory results for the detection in real samples, demonstrating the feasibility of the proposed sensor in detecting of DON in such products.
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Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen-associated molecular patterns (PAMPs) and activating PAMP-triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad-spectrum diseases in agricultural production through the utilization of plant immune receptors.
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PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Desoxicitidina , Gencitabina , Compostos de Fenilureia , Quinolinas , Humanos , Masculino , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/mortalidade , Feminino , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Pessoa de Meia-Idade , Idoso , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/mortalidade , Estudos Retrospectivos , Infusões Intra-Arteriais , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Artéria Hepática , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Compostos OrganoplatínicosRESUMO
Aromatic monomers obtained by selective depolymerization of the lignin ß-O-4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one-pot catalytic lignin ß-O-4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side-chains. This cascade consists of selective acceptorless dehydrogenation of the γ-hydroxy group, subsequent retro-aldol reaction cleaving the Cα-Cß bond followed by in situ acceptorless decarbonylation of the formed aldehydes. This three-step cascade reaction, catalyzed by an iridium(I)-BINAP complex, resulted in 75% 1,2-dimethoxybenzene from G-type lignin dimers alongside syngas (CO:H2 ≈ 1.4:1). Applying this method to a synthetic G-type polymer, 11 wt% 1,2-dimethoxybenzene was obtained. This versatile compound can be easily transformed into 3,4-dimethoxyphenol, a valuable precursor for pharmaceutical synthesis, through enzymatic catalytic approach. Moreover, the hydrodeoxygenation potential of 1,2-dimethoxybenzene offers a pathway to produce valuable cyclohexane or benzene derivatives, presenting enticing opportunities for sustainable chemical transformations without the necessity for phenolic mixture upgrading via dealkylation.
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The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives. We show here that human naive pluripotent stem cell (PSC) to hypoblast differentiation proceeds via reversion to a transitional ICM-like state from which the hypoblast emerges in concordance with the trajectory in human blastocysts. We identified a window when fibroblast growth factor (FGF) signaling is critical for hypoblast specification. Revisiting FGF signaling in human embryos revealed that inhibition in the early blastocyst suppresses hypoblast formation. In vitro, the induction of hypoblast is synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports and establishes a conservation in lineage specification between mice and humans. Overall, this study demonstrates the utility of human naive PSC-based models in elucidating the mechanistic features of early human embryogenesis.
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Diferenciação Celular , Linhagem da Célula , Fatores de Crescimento de Fibroblastos , Células-Tronco Pluripotentes , Humanos , Fatores de Crescimento de Fibroblastos/metabolismo , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Blastocisto/metabolismo , Blastocisto/citologia , Animais , Transdução de Sinais , Camundongos , Modelos Biológicos , Camadas Germinativas/metabolismo , Camadas Germinativas/citologiaRESUMO
The leader-following consensus (LFC) issue is investigated in this paper for multi-agent systems (MASs) subject to actuator saturation with semi-Markov switching topologies (SMST). A new consensus protocol is proposed by using a semi-Markov process to model the switching of network topologies. Compared to the traditional Markov switching topologies, the SMST is more general and practical because the transition rates are time-varying. By using the local sector conditions and a suitable Lyapunov-Krasovskii functional, some sufficient conditions are proposed such that the leaderfollowing mean-square consensus is locally achieved. Based on the derived sufficient conditions, an optimization problem is analyzed to determine the consensus feedback gains and to find a maximal estimate of the domain of consensus attraction (DOCA) of a closed-loop model. At the end, a numerical case is presented to verify the performance of the design method.
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Introduction: Vascular calcification is a major cause of cardiovascular accidents in patients with type 2 diabetes mellitus. This study aimed to investigate the impact of carbohydrates on gut microbiota and aortic calcification in diabetic ApoE-/- mice. Methods: The diabetic ApoE-/- mice were randomly divided into 4 groups: ketogenic diet group, low carbohydrate diet group, medium carbohydrate diet group, and high carbohydrate diet group. The mice were fed continuously for 6 months, with blood glucose, blood ketone and body weight monitored monthly. Lipid metabolism indicators and inflammatory factors were detected using ELISA. The intestinal barrier, atherosclerotic lesion areas, and vascular calcifications were analyzed based on their morphology. Gut microbiota was analyzed using 16S rRNA genes. Results: We found that ketogenic diet played some roles improving glucose, lipid metabolism, and inflammation. Ketogenic diet could improve the intestinal barrier to some extent and increase intestinal bacteria. Compared to the other three groups, the relative abundance of genus Allobaculum, species Blautia producta and Clostridium Ramosum in the ketogenic diet group was significantly increased (P <0.05), which has protective effects in diabetic ApoE-/- mice. Conclusion: Ketogenic diet could delay the onset of aortic atherosclerosis, aortic calcification and improve intestinal barrier function in diabetic ApoE-/- mice.
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BACKGROUND AND OBJECTIVE: Cardiac computed tomography angiography (CTA) is the preferred modality for preoperative planning in aortic valve stenosis. However, it cannot provide essential functional hemodynamic data, specifically the mean transvalvular pressure gradient (MPG). This study aims to introduce a computational fluid dynamics (CFD) approach for MPG quantification using cardiac CTA, enhancing its diagnostic value. METHODS: Twenty patients underwent echocardiography, cardiac CTA, and invasive catheterization for pressure measurements. Cardiac CTA employed retrospective electrocardiographic gating to capture multi-phase data throughout the cardiac cycle. We segmented the region of interest based on mid-systolic phase cardiac CTA images. Then, we computed the average flow velocity into the aorta as the inlet boundary condition, using variations in end-diastolic and end-systolic left ventricular volume. Finally, we conducted CFD simulations using a steady-state model to obtain pressure distribution within the computational domain, allowing for the derivation of MPG. RESULTS: The mean value of MPG, measured via invasive catheterization (MPGInv), echocardiography (MPGEcho), and cardiac CTA (MPGCT), were 51.3 ± 28.4 mmHg, 44.8 ± 19.5 mmHg, and 55.8 ± 25.6 mmHg, respectively. In comparison to MPGInv, MPGCT exhibited a higher correlation of 0.91, surpassing that of MPGEcho, which was 0.82. Moreover, the limits of agreement for MPGCT ranged from -27.7 to 18.7, outperforming MPGEcho, which ranged from -40.1 to 18.0. CONCLUSIONS: The proposed method based on cardiac CTA enables the evaluation of MPG for aortic valve stenosis patients. In future clinical practice, a single cardiac CTA examination can comprehensively assess both the anatomical and functional hemodynamic aspects of aortic valve disease.
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Angiografia por Tomografia Computadorizada , Hemodinâmica , Humanos , Angiografia por Tomografia Computadorizada/métodos , Masculino , Feminino , Idoso , Hemodinâmica/fisiologia , Pessoa de Meia-Idade , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Valvopatia Aórtica/diagnóstico por imagem , Valvopatia Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Modelos Cardiovasculares , Ecocardiografia/métodosRESUMO
BACKGROUND AND PURPOSE: Recently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients. METHODS: This research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients' overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell's C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan-Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26. RESULTS: This study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell's C-index in the training and validation sets of the model was 0.85 (95% CI 0.76-0.93) and 0.88 (95% CI 0.76-0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy. CONCLUSION: This study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Masculino , Feminino , Estudos Retrospectivos , Prognóstico , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/imunologia , China/epidemiologia , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Nomogramas , Adulto , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.
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Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in human embryo research, makes investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin embryos. In this study, a microthermoformed-based microwell screening platform is used to identify conditions that efficiently induce monochorionic twins in human stem cell-based blastocyst models, termed "twin blastoids". These twin blastoids contain a cystic GATA3+ trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, ready for implantation. This is functionally tested in a microfluidic chip-based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential. In conclusion, the development of technology enabling large-scale formation of twin blastoids, coupled with high-sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.
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Gemelaridade Monozigótica , Humanos , Feminino , Gravidez , Blastocisto/citologia , Embrião de Mamíferos/citologia , Córion/citologia , Bioengenharia/métodos , Modelos Biológicos , Implantação do EmbriãoRESUMO
Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by xanthomatous infiltration of affected organs. We present a case of a 62-year-old man with ECD initially presenting with constrictive pericarditis. Comprehensive imaging revealed systemic involvement, including the skeleton, orbit, pituitary, lung, kidney, and retroperitoneum, despite the absence of related symptoms. The diagnosis of ECD was eventually confirmed through histopathological evidence from a CT-guided biopsy. The patient responded well to interferon-α2b treatment, with gradual symptom amelioration and improvement in imaging and laboratory findings over a 5-month follow-up period. This case highlights the importance of considering ECD in the differential diagnosis of constrictive pericarditis and the utility of multimodal imaging for accurate diagnosis and management of this rare disease. The patient's positive response to treatment also highlights the potential for effective management of ECD, particularly with early diagnosis and intervention.
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The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.
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ABSTRACT: Myocardial fibrosis, a common complication of myocardial infarction (MI), is characterized by excessive collagen deposition and can result in impaired cardiac function. The specific role of CD137 in the development of post-MI myocardial fibrosis remains unclear. Thus, this study aimed to elucidate the effects of CD137 signaling using CD137 knockout mice and in vitro experiments. CD137 expression levels progressively increased in the heart after MI, particularly in myofibroblast, which play a key role in fibrosis. Remarkably, CD137 knockout mice exhibited improved cardiac function and reduced fibrosis compared with wild-type mice at day 28 post-MI. The use of Masson's trichrome and picrosirius red staining demonstrated a reduction in the infarct area and collagen volume fraction in CD137 knockout mice. Furthermore, the expression of alpha-smooth muscle actin and collagen I, key markers of fibrosis, was decreased in heart tissues lacking CD137. In vitro experiments supported these findings because CD137 depletion attenuated cardiac fibroblast differentiation, and migration, and collagen I synthesis. In addition, the administration of CD137L recombinant protein further promoted alpha-smooth muscle actin expression and collagen I synthesis, suggesting a profibrotic effect. Notably, the application of an inhibitor targeting the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway attenuated the profibrotic effects of CD137L. To conclude, this study provides evidence that CD137 plays a significant role in promoting myocardial fibrosis after MI. Inhibition of CD137 signaling pathways may hold therapeutic potential for mitigating pathological cardiac remodeling and improving post-MI cardiac function.
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Modelos Animais de Doenças , Fibrose , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Remodelação Ventricular , Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular/efeitos dos fármacos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Masculino , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Miofibroblastos/enzimologia , Sistema de Sinalização das MAP Quinases , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/enzimologia , Ligante 4-1BB/metabolismo , Ligante 4-1BB/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Actinas/metabolismo , Células Cultivadas , Transdução de Sinais , Movimento Celular , Camundongos , Função Ventricular Esquerda , Diferenciação Celular , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/efeitos dos fármacosRESUMO
Carbon dot (C-dot) separation/purification is not only a fundamental chemical issue but also an essential precondition for revealing C-dots' true nature. To date, adequate separation of C-dots has remained an open question due to the lack of an appropriate fine separation system. Herein, we discover and reveal that polyamide chromatography can provide versatile and powerful performances for C-dot separation. By a joint study of experiments and all-atom molecular dynamics simulations, we demonstrate that multiple interaction forces, including electrostatic repulsion/attraction, hydrogen bond, and van der Waals effects, exist simultaneously among the stationary phase, mobile phase, and the separated C-dots. Furthermore, the magnitude of these forces is dependent on the surface chemistry of the separated C-dots and the nature of the used mobile phases, providing a theoretical basis and experimental operability for C-dot separation. So, the proposed system possesses the capacity for adequately separating hydrophilic, amphiphilic, and lipophilic C-dots. The polyamide chromatography, due to its versatile and powerful separation performances, not only provides more thorough separation effects but also helps to correct our false perceptions from inadequate purified C-dots.
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Herein, novel nanozyme mimics MoO3/MIL-125-NH2 were reported and conjugated with bacteriophages as a new electrochemical probe for high sensitivity and specific electrochemical detection of staphylococcus aureus. The excellent peroxidase-like activity of MoO3/MIL-125-NH2 composites was attributed to the integration of MIL-125-NH2 with MoO3, which can boost the generation of superoxide radicals (O⢠2-) and thus promote the oxidation of TMB in the presence of H2O2. In this work, two bacteriophages named SapYZU04 and SapYZU10 were isolated from sewage samples by using staphylococcus aureus YZUsa12 as the host. In comparison, MoO3/MIL-125-NH2@SapYZU04 was selected as a recognition agent. The DPV current declined linearly with staphylococcus aureus YZUsa12 concentration in the range of 101-108 CFU mL-1, with a low detection limit of 16 CFU mL-1 (S/N = 3). 20 strains including 13 host strains and 7 non-host strains were used to evaluate the selectivity of the proposed sensor. Regardless of the differences in the degrees of lytic performance for phage SapYZU04, all selected host strains can be screened with merely the same DPV current. Host spectrum-oriented bacteriophage sensing is of great importance for the practical application of bacteriophage-based biosensors in the future.
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Bacteriófagos , Técnicas Biossensoriais , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Peróxido de Hidrogênio , PeroxidasesRESUMO
This study investigates an asynchronous sampled-data control problem of vehicular platoons, with heterogeneous sampling, subjected to actuator delays. Without a synchronized clock, a completely asynchronous sampled-data controller is designed for each follower, where the state of the ith follower itself and its neighboring vehicles are sampled at their own sampling time instants. The caused closed-loop tracking error dynamics for the entire platoon considering the effect of the nonuniform sampling time intervals, heterogeneous vehicle dynamics, inter-vehicle topology and heterogeneous time delays. To simplify the stability analysis and controller design, the tracking-error dynamics of the entire platoon are decomposed into individual subsystems with reduced-order dynamics. Based on Lyapunov stability theory, the optimal conditions are explored to design an asynchronous sampled-data controller to guarantee the desired stability performance. Moreover, the exact values for the maximum allowable sampling interval and time delay are calculated for each follower using the designed feedback controller gain. The proposed asynchronous sampled-data control method is extended to a vehicular platoon using an event-based sampling scheme. Numerical examples are used to verify the effectiveness of the proposed sampled-data control method.
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INTRODUCTION: The waning antibody levels several months after prime vaccination and the persistent epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world have generated great interest in the evaluation of a booster dose. We aimed to assess the safety and immunogenicity of a homologous booster dose of the recombinant adenovirus type 5-vectored coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV). METHODS: In this trial, we recruited healthy adults aged 18-60 years who had received one dose of Ad5-nCoV vaccine (low, middle, or high dose) in the previous phase 1 trial approximately 6 months earlier, and then all participants received a booster dose of 5 × 1010 viral particles (low dose) intramuscularly. The primary outcome was the incidence of adverse reactions within 14 days after booster vaccination. The specific binding antibodies were measured by enzyme-linked immunosorbent assay and the neutralizing antibody responses were assessed with live SARS-CoV-2 and pseudovirus neutralization assay. The cellular immune responses were analyzed by enzyme-linked immunospot assay and intracellular cytokine staining. RESULTS: From September 26 to 28, 2020, 108 volunteers were recruited and 89 eligible participants (52% male) were enrolled and received a booster dose of Ad5-nCoV vaccine: 28 (31%) had received a low prime dose, 30 (34%) a middle prime dose, and 31 (35%) a high prime dose in the previous phase 1 trial. All participants were included in the safety analysis and immunogenicity was assessed in 88 (99%) participants. Twenty-three (82%) participants in the low prime dose group, 23 (77%) participants in the middle prime dose group, and 26 (84%) participants in the high prime dose group reported at least one adverse reaction within the first 14 days post booster. Pain at the injection site and fatigue were the most common adverse reactions. Most adverse reactions were mild or moderate in all groups and no vaccine-related severe adverse event was noted within 12 months after booster vaccination. Neutralizing antibodies increased moderately at day 14 and peaked at 28 days post booster. T cell responses were also boosted at 14 days after vaccination. CONCLUSIONS: A homologous booster of Ad5-nCoV vaccine is well tolerated and immunogenic in healthy adults aged 18-60 years who had received a priming dose of Ad5-nCoV 6 months previously. The neutralizing antibodies against SARS-CoV-2 peaked at day 28 and specific T cell responses were noted at day 14 after booster. Ad5-nCoV vaccine can be considered as a homologous booster 6 months after a priming dose. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04568811.
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Chaphamaparvovirus carnivoran2 (feline chaphamaparvovirus, FeChPV) is a novel feline parvovirus originally detected in Canadian cats in 2019, and it has also been identified in domestic cats in other nations. To evaluate the prevalence and genetic diversity of FeChPV in China, rectal swabs of pet cats from Henan, Guangdong, Anhui, Zhejiang, and Inner Mongolia provinces were collected. Of the 230 samples subjected to nested polymerase chain reaction, 6 (2.6%) tested positive for FeChPV. Although all positive samples were from cats with diarrhea, statistical analyses revealed no correlation between the presence of the virus and clinical symptoms (p > 0.05). Phylogenetic trees of nonstructural protein 1 (NS1) and capsid protein (VP1) demonstrated that these six new strains formed a major branch with other reference FeChPV strains and considerably differed from Chaphamaparvoviru carnivoran1. Moreover, recombination analysis revealed that the FeChPV strain CHN20201025, previously detected in a dog, was a recombinant and strains CHN200228 and CHN180917, identified in this study, were the closest relatives to the parental strains. The findings of this study and a previous study wherein FeChPV was detected in dogs suggest that FeChPV can propagate between species. Additionally, these findings indicate that the genetic diversity of FeChPV can provide an insight into the epidemiological status of FeChPV in China.
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Poria cocos peel residue (PCPR) still contains much soluble dietary fiber (SDF), steam explosion (SE) treatment was applied to PCPR to create a superior SDF. Steam pressure of 1.2 MPa, residence period of 120 s, and moisture content of 13% were the optimized parameters for SE treatment of PCPR. Under optimized circumstances, SE treatment of PCPR enhanced its SDF yield from 5.24% to 23.86%. Compared to the original SDF, the SE-treated SDF displayed improved enzyme inhibition, including the inhibition of α-amylase and pancreatic lipase, also enhanced water holding, oil holding, water swelling, nutrient adsorption including cholesterol, nitrite ions, and glucose and antioxidant abilities. Additionally, it had a decreased molecular weight, improved thermal stability, and a rough surface with many pores of different sizes. Given that SDF had been improved physiochemical and functional characteristics thanks to SE treatment, it might be the excellent functional ingredient for the food business.