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Background: Retinoblastoma is considered a lethal but curable malignancy often presenting in childhood. We investigated its global, regional, and national burden among infants and young children from 1990 to 2021. Methods: We obtained data on retinoblastoma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Trends were analysed using joinpoint regression to calculate annual percentage changes. Spearman's rank correlation and locally estimated scatterplot smoothing regression were used to assess the relationship between retinoblastoma burden and sociodemographic index. Findings: In 2021, the global incidence, prevalence, mortality, and DALYs of retinoblastoma were 0.82 (95% uncertainty interval [UI], 0.48-1.10), 7.46 (95% UI, 4.42-10.08), 0.37 (95% UI, 0.22-0.51), and 32.81 (95% UI, 19.9-45.21), respectively. From 1990 to 2021, the global incidence and prevalence rates of retinoblastoma increased, with average annual percentage changes (AAPCs) of 0.67 (95% confidence interval [CI], 0.49-0.85] and 0.68 (95% CI, 0.50-0.86), respectively. Conversely, those of related mortality and DALYs decreased, with AAPCs of -0.64 (95% CI, -0.79 to -0.49) and -0.63 (95% CI, -0.78 to -0.48), respectively. Children aged 2-4 years and those in low-income regions exhibited the highest burden. Negative correlations were found between sociodemographic index and retinoblastoma burden. Interpretation: Advancements in retinoblastoma detection and treatment have increased its reported incidence and prevalence while reducing its mortality and DALYs. Nonetheless, substantial socioeconomic and geographic disparities persist. In low-income countries, the incidence has decreased, possibly reflecting challenges such as limited healthcare access and underreporting, necessitating targeted interventions and improved healthcare access. Funding: National Key R&D Project of China (2020YFA0112701), Natural Science Foundation of Guangdong Province (2024A1515013058), and Science and Technology Program of Guangzhou, China (202206080005).
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BACKGROUND: The role of Myocyte Enhancer Factor 2 C (MEF2C) in lung adenocarcinoma (LUAD) is unclear. OBJECTIVE: To address this gap in knowledge, we employed bioinformatics analysis and experimental validation in this study. METHODS: This study investigated MEF2C expression across a spectrum of cancers, with a specific focus on lung adenocarcinoma (LUAD), utilizing Cancer Genome Atlas (TCGA) data to assess its potential as a diagnostic marker. The study also investigated correlations between MEF2C expression and clinical traits and prognostic indicators of LUAD. Additionally, this study also delved into the regulatory mechanisms of MEF2C, examining its connections to immune system interactions, immune checkpoint genes, tumor mutational burden (TMB), and the sensitivity of LUAD to various drugs. Through single-cell sequencing of LUAD cells and genetic variation of MEF2C in LUAD, we explored the expression of MEF2C in cell lines and verified it by quantitative real-time PCR (qRT-PCR). RESULTS: MEF2C exhibited aberrant expression in both pan-cancer and LUAD. In individuals with LUAD, diminished levels of MEF2C expression were notably linked to the effectiveness of primary therapy outcome (p = 0.025), gender (p < 0.001), and the subdivision of anatomic neoplasms 2 (p = 0.011). A decline in MEF2C levels was also found to be significantly related to reduced overall survival (OS) in LUAD patients (p = 0.026). The presence of MEF2C was recognized as a standalone factor predictive of prognosis in LUAD (p = 0.029). MEF2C was found to be involved in multiple biological pathways, such as those involving cell adhesion molecules. Additionally, its expression was correlated with the extent of immune cell presence, the activity of immune checkpoint genes, and TMB in LUAD. Notably, an inverse relationship was observed between MEF2C expression and the sensitivity to several agents, including Topotecan, Irinotecan, Panobinostat, Nilotinib, and Tp38-279, within the context of LUAD. Furthermore, MEF2C was found to be significantly negatively regulated in LUAD cell lines. CONCLUSION: The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.
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Rapid and sensitive detection of the concentration of sialic acid (SA) in serum is crucial for early tumor screening and prognostic assessment; however, it still remains challenging. Here, we propose a novel kind of hydrogel grating sensor with boron affinity and molecular imprinting effects (B-MIP) for the rapid and sensitive detection of SA concentration in serum. The hydrogel gratings feature uniform surface relief microstructures and incorporate highly specific recognition binding sites into SA molecules provided by boron affinity and molecular imprinting. The periodic nanoridges of hydrogel gratings increase the specific surface area contacting the environmental solution; therefore, fast detection can be achieved within 2 min. Upon recognition of SA molecules, the height of hydrogel gratings changes at the nanoscale, causing a change in the diffraction efficiency of the hydrogel gratings. The B-MIP hydrogel grating sensors have highly specific binding sites to SA molecules distributed throughout the whole hydrogel and can preferentially and selectively recognize and respond to the SA molecules even in the presence of interference substances glucose and fructose with high concentrations. The B-MIP hydrogel grating sensors are effectively applicable for the rapid and sensitive detection of SA concentrations in real serum samples with satisfactory accuracy and precision. Our approach provides an excellent strategy to address the current challenges in SA detection and provides new insights into the detection of tumor markers in serum, thereby opening up new ways to accurately detect complex biological samples in analytical science.
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Biomarcadores Tumorais , Boro , Hidrogéis , Impressão Molecular , Ácido N-Acetilneuramínico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Humanos , Boro/química , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/análise , Hidrogéis/química , Técnicas BiossensoriaisRESUMO
The copolymerization of CO2 and epoxides presents a transformative approach to converting greenhouse gases into aliphatic polycarbonates (CO2-PCs), thereby reducing the polymer industry's dependence on fossil resources. Over the past 50 years, a wide array of metallic catalysts, both heterogeneous and homogeneous, have been developed to achieve precise control over polymer selectivity, sequence, regio-, and stereoselectivity. This review details the evolution of metal-based catalysts, with a particular focus on the emergence of organoborane catalysts, and explores how these catalysts effectively address kinetic and thermodynamic challenges in CO2/epoxides copoly2merization. Advances in the synthesis of CO2-PCs with varied sequence and chain architectures through diverse polymerization protocols are examined, alongside the applications of functional CO2-PCs produced by incorporating different epoxides. The review also underscores the contributions of computational techniques to our understanding of copolymerization mechanisms and highlights recent advances in the closed-loop chemical recycling of CO2-sourced polycarbonates. Finally, the industrialization efforts of CO2-PCs are discussed, offering readers a comprehensive understanding of the evolution and future potential of epoxide copolymerization with CO2.
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OBJECTIVE: To examine associations among experiences of racial discrimination, perceived stress, and birth satisfaction and to test if perceived stress mediates the relationship between racial discrimination and birth satisfaction among Black women in the postpartum period. DESIGN: Secondary analysis of data from the Biosocial Impact on Black Births study. SETTING: A postpartum unit of a large hospital in Central Florida. PARTICIPANTS: Black women (N = 154) in the postpartum period. METHODS: Participants completed the lifetime Experiences of Discrimination scale, Perceived Stress Scale and Birth Satisfaction Scale-Revised between 24 hours and 23 days after birth. We calculated descriptive statistics and Spearman's ρ correlation coefficients to evaluate associations among variables. We used multiple linear regression to evaluate perceived stress as a mediator between racial discrimination and birth satisfaction. RESULTS: Racial discrimination had a positive association with perceived stress (ß = 2.445, p = .03), and perceived stress had a negative association with birth satisfaction (ß = -0.221, p = .02). Racial discrimination had no significant direct effect on birth satisfaction (ß = -0.091, p = .94); therefore, perceived stress did not mediate the relationship. CONCLUSION: More experiences of discrimination over the life span were associated with higher levels of perceived stress. Participants who reported higher levels of perceived stress reported lower levels of birth satisfaction. Our study adds to the body of knowledge regarding associations between racial discrimination and perceived stress and perceived stress and birth satisfaction.
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Purpose: We aimed to examine the normative profile of crystalline lens power (LP) and its associations with ocular biometric parameters including age, axial length (AL), spherical equivalent refraction (SE), corneal radius (CR), lens thickness, anterior chamber depth, and AL/CR ratio among a cynomolgus monkey colony. Methods: This population-based cross-sectional Non-human Primate Eye Study recruited middle-aged subjects in South China. All included macaques underwent a detailed ophthalmic examination. LP was calculated using the modified Bennett's formula, with biometry data from an autorefractometer and A-scan. SPSS version 25.0 was used for statistical analysis. Results: A total of 301 macaques with an average age of 18.75 ± 2.95 years were collected in this study. The mean LP was 25.40 ± 2.96 D. Greater LP was independently associated with younger age, longer AL, and lower SE (P = 0.028, P = 0.025, and P = 0.034, respectively). LP showed a positive correlation with age, SE, CR, AL, lens thickness, and anterior chamber depth, whereas no correlation was observed between LP and AL/CR ratio. Conclusions: Our results suggested the LP distribution in the nonhuman primate colony and indicated that AL and SE strongly influenced the rate of LP. Therefore, this study contributed to a deeper understanding of the relative significance of the LP on the optics of the crystalline lens study.
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Comprimento Axial do Olho , Biometria , Cristalino , Macaca fascicularis , Refração Ocular , Animais , Cristalino/anatomia & histologia , Estudos Transversais , Refração Ocular/fisiologia , Masculino , Feminino , Biometria/métodos , Câmara Anterior/anatomia & histologia , Córnea/anatomia & histologiaRESUMO
In the glycerolysis process for diacylglycerol (DAG) preparation, free lipases suffer from poor stability and the inability to be reused. To address this, a cost-effective immobilized lipase preparation was developed by cross-linking macroporous resin with poly (ethylene glycol) diglycidyl ether (PEGDGE) followed by lipase adsorption. The selected immobilization conditions were identified as pH 7.0, 35 °C, cross-linking agent concentration 2.0%, cross-linking time 4 h, lipase amount 5 mg/g of support, and adsorption time 4 h. Enzymatic properties of the immobilized lipase were analyzed, revealing enhanced pH stability, thermal stability, storage stability, and operational stability post-immobilization. The conditions for immobilized enzyme-catalyzed glycerolysis to produce DAG were selected, demonstrating the broad applicability of the immobilized lipase. The immobilized lipase catalyzed glycerolysis reactions using various oils as substrates, with DAG content in the products ranging between 35 and 45%, demonstrating broad applicability. Additionally, the changes during the repeated use of the immobilized lipase were characterized, showing that mechanical damage, lipase leakage, and alterations in the secondary structure of the lipase protein contributed to the decline in catalytic activity over time. These findings provide valuable insights for the industrial application of lipase.
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Diglicerídeos , Estabilidade Enzimática , Enzimas Imobilizadas , Lipase , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Lipase/química , Lipase/metabolismo , Diglicerídeos/química , Concentração de Íons de Hidrogênio , Glicerol/química , Temperatura , Eurotiales/enzimologia , Biocatálise , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismoRESUMO
Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.
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Macaca fascicularis , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Animais , Células Ganglionares da Retina/citologia , Masculino , Estudos Transversais , Tomografia de Coerência Óptica/métodos , Feminino , Disco Óptico/anatomia & histologia , Disco Óptico/diagnóstico por imagem , Comprimento Axial do Olho/anatomia & histologia , Valores de Referência , Biometria , Erros de Refração/fisiopatologiaRESUMO
Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance.
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BACKGROUNDS: Glycerolysis, with its advantages of readily available raw materials, simple operation, and mild reaction conditions, is a primary method for producing diacylglycerol (DAG). However, enzymatic glycerolysis faces challenges such as high enzyme costs, low reuse efficiency, and poor stability. The study aims to develop a cost-effective immobilized enzyme by covalently binding lipase to pre-activated carriers through the selection of suitable lipases, carriers, and activating agents. The optimization is intended to improve the glycerolysis reaction for efficient DAG production. RESULTS: Lipase CN-TL (from Thermomyces lanuginosus) was selected through glycerolysis reaction and molecular docking to catalyze the glycerolysis reaction. Optimizing the immobilization method by covalently binding CN-TL to poly(ethylene glycol) diglycidyl ether (PEGDGE)-preactivated resin LX-201A resulted in the preparation of the immobilized enzyme TL-PEGDGE-LX. The immobilized enzyme retained over 90% of its initial activity after five consecutive reactions, demonstrating excellent reusability. The DAG content in the product remained at 84.8% of its initial level, further highlighting the enzyme's potential for reusability and its promising applications in the food and oil industries. CONCLUSIONS: The immobilized lipase TL-PEGDGE-LX, created by covalently immobilizing lipase CN-TL on PEGDGE-preactivated carriers, demonstrated broad applicability and excellent reusability. This approach offers an economical and convenient immobilization strategy for the enzymatic glycerolysis production of DAG. © 2024 Society of Chemical Industry.
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BACKGROUND: Black pregnant women who experience racial discrimination are at an increased risk of psychological distress. Studies have not adequately addressed if social support may moderate the association between experiences of racial discrimination and psychological distress among Black pregnant women. OBJECTIVE: We sought to examine the moderating effect of social support on the association between experiences of racial discrimination and psychological distress among Black pregnant women. METHODS: We report findings based on cross-sectional data collected from 599 Black pregnant women enrolled in a prospective cohort study prior to the COVID-19 pandemic. Women completed questionnaires about experiences of racial discrimination (Experiences of Discrimination), social support (MOS Social Support Survey), and psychological distress (Psychological General Wellbeing Index). RESULTS: Women had an average age of 26 ± 5 years and gestational age at data collection of 17 ± 6 weeks. Approximately 53% of women reported ever experiencing racial discrimination in at least one situation, and 54% reported psychological distress. After adjustment for covariates, racial discrimination was associated with a 2.2-fold increase in psychological distress (odds ratio [OR] = 2.24; 95% confidence interval [CI] 1.35-3.70; P = .002). Low social support (scores below the median) was associated with a 3.8-fold higher likelihood of psychological distress (OR = 3.84, 95% CI 2.27-6.48, P < .001). Social support did not moderate the association of lifetime experiences of racial discrimination with psychological distress. CONCLUSIONS: Findings of the study contribute to evidence that lifetime experiences of racial discrimination and low levels of social support relate to psychological distress among Black pregnant women.
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Negro ou Afro-Americano , Gestantes , Angústia Psicológica , Racismo , Apoio Social , Adulto , Feminino , Humanos , Gravidez , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Estudos Transversais , Gestantes/psicologia , Gestantes/etnologia , Estudos Prospectivos , Racismo/psicologia , Estresse Psicológico/psicologia , Estresse Psicológico/etnologia , Inquéritos e QuestionáriosRESUMO
KEY MESSAGE: Exogenous application of 24-epibrassinolide can alleviate oxidative damage, improve photosynthetic capacity, and regulate carbon and nitrogen assimilation, thus improving the tolerance of grapevine (Vitis vinifera L.) to drought stress. Brassinosteroids (BRs) are a group of plant steroid hormones in plants and are involved in regulating plant tolerance to drought stress. This study aimed to investigate the regulation effects of BRs on the carbon and nitrogen metabolism in grapevine under drought stress. The results indicated that drought stress led to the accumulation of superoxide radicals and hydrogen peroxide and an increase in lipid peroxidation. A reduction in oxidative damage was observed in EBR-pretreated plants, which was probably due to the improved antioxidant concentration. Moreover, exogenous EBR improved the photosynthetic capacity and sucrose phosphate synthase activity, and decreased the sucrose synthase, acid invertase, and neutral invertase, resulting in improved sucrose (190%) and starch (17%) concentrations. Furthermore, EBR pretreatment strengthened nitrate reduction and ammonium assimilation. A 57% increase in nitrate reductase activity and a 13% increase in glutamine synthetase activity were observed in EBR pretreated grapevines. Meanwhile, EBR pretreated plants accumulated a greater amount of proline, which contributed to osmotic adjustment and ROS scavenging. In summary, exogenous EBR enhanced drought tolerance in grapevines by alleviating oxidative damage and regulating carbon and nitrogen metabolism.
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Brassinosteroides , Resistência à Seca , Fotossíntese , Esteroides Heterocíclicos , Vitis , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Carbono/metabolismo , Glucosiltransferases/metabolismo , Glutamato-Amônia Ligase/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Nitrato Redutase/metabolismo , Nitrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Esteroides Heterocíclicos/metabolismo , Esteroides Heterocíclicos/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Vitis/efeitos dos fármacos , Vitis/metabolismo , Vitis/fisiologiaRESUMO
Polygoni Multiflori Caulis (PMC) is commonly used in clinical practice. While the adverse reactions of Polygoni Multiflori Radix (RPM) are well-known, the potential adverse reactions of PMC are often neglected. This article aims to clarify the relationship between hepatotoxic components in PMC and its various producing areas. This study provides a qualitative and quantitative analysis of PMC from various regions, which can serve as a basis for safe usage.
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In this study, the impact of ammonia nitrogen stress on juvenile four-finger threadfin in pond culture was examined. The 96-hour median lethal concentration (LC50-96h) and safe concentration of ammonia nitrogen were assessed in juveniles with a body weight of 7.4 ± 0.6 g using ecotoxicological methods. The study design included a stress group exposed to LC50-96h levels of ammonia nitrogen and a control group without ammonia nitrogen exposure. To examine the physiological, biochemical, and metabolic effects of ammonia nitrogen on gill tissue, gill tissue samples were collected after 12, 24, 48, and 96 h of stress, with a resumption of treatment after 48 h. Compared to the control group, ammonia nitrogen adversely affected juvenile four-finger threadfin, with LC50-96h and safe concentration values of 20.70 mg/L and 2.07 mg/L, respectively. Exposure to ammonia nitrogen resulted in substantial gill damage, including fusion of lamellae, epithelial cell loss, and proliferation of chlorine-secreting cells. This tissue damage persisted even after a 48-h recovery period. Ammonia nitrogen stress triggered an increase in antioxidant enzyme activity (superoxide dismutase, catalase, and glutathione peroxidase) and malondialdehyde levels in gills, indicating oxidative stress from 12 h onwards. Although enzyme activity decreased over time, oxidative stress persisted even after recovery, suggesting an ongoing need for antioxidant defense. Metabolomics analysis showed significant alterations in 423 metabolites under ammonia nitrogen stress. Key metabolites such as L-arginine, taurine, 20-hydroxyarachidonic acid, 11,12-dihydroxy-5Z, 8Z, and 14Z eicosotrienic acid followed an increasing trend; uridine, adenosine, L-glutathione, and thymidine 5'-triphosphate followed a decreasing trend. These changes reflect metabolic adaptations to stress. In enriched metabolic pathways, the main differential pathways are membrane transport, lipid metabolism, and amino acid metabolism. After 48 h, significant differences were observed in 396 metabolites compared to the control group. Notably, L-arginine, choline, and L-histidine increased, while linoleic acid, adenosine, and glutathione decreased. Amino acid and lipid metabolism pathways were key affected pathways. Under ammonia nitrogen stress, juvenile four-finger threadfin increased the synthesis of unsaturated and saturated fatty acids to cope with low temperatures and bolster immune function by consuming spermidine. This adaptation helps to clear peroxides generated during fatty acid synthesis, thereby protecting cells from oxidative damage. This study provides insights for pond aquaculture and breeding of ammonia nitrogen-tolerant fish strains.
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Amônia , Brânquias , Poluentes Químicos da Água , Animais , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Amônia/toxicidade , Poluentes Químicos da Água/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Peixes/fisiologia , Peixes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Nitrogênio/metabolismo , Catalase/metabolismo , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Skeletal muscle injury is one of the most common sports injuries; if not properly treated or not effective rehabilitation treatment after injury, it can be transformed into chronic cumulative injury. Curcumin, an herbal ingredient, has been found to promote skeletal muscle injury repair and regeneration. The Wnt5a pathway is related to the expression of myogenic regulatory factors, and Ca2+ promotes the differentiation and fusion process of myoblasts. This study explored the effect and mechanism of curcumin on myoblast differentiation during the repair and regeneration of injured skeletal muscle and its relationship with the Wnt5a pathway and Ca2+ channel. METHODS: Myogenic differentiation of C2C12 cells was induced with 2% horse serum, and a mouse (male, 10 weeks old) model of acute skeletal muscle injury was established using cardiotoxin (20 µL). In addition, we constructed a Wnt5a knockdown C2C12 cell model and a Wnt5a knockout mouse model. Besides, curcumin was added to the cell culture solution (80 mg/L) and fed to the mice (50 mg/kg). Fluorescence microscopy was used to determine the concentration of Ca2+. Western blot and RT-qPCR were used to detect the protein and mRNA levels of Wnt5a, CaN, NFAT2, MyoD, Myf5, Pax7, and Myogenin. The expression levels of MyoD, Myf5, Myogenin, MHC, Desmin, and NFAT2 were detected using immunofluorescence techniques. In addition, MyoD expression was observed using immunohistochemistry, and morphological changes in mouse muscle tissue were observed using HE staining. RESULTS: During myoblast differentiation and muscle regeneration, Wnt5a expression was upregulated (P < 0.001) and the Wnt5a signalling pathway was activated. Wnt5a overexpression promoted the expression of MyoD, Myf5, Myogenin, MHC, and Desmin (P < 0.05), and conversely, knockdown of Wnt5a inhibited their expression (P < 0.001). The Wnt5a pathway mediated the opening of Ca2+ channels, regulated the expression levels of CaN, NFAT2, MyoD, Myf5, Myogenin, MHC, and Desmin (P < 0.01) and promoted the differentiation of C2C12 myoblasts and the repair and regeneration of injured skeletal muscle. The expression of Wnt5a, CaN, NFAT2, MyoD, Myogenin, Myf5, and MHC in C2C12 myoblast was significantly increased after curcumin intervention (P < 0.05); however, their expression decreased significantly after knocking down Wnt5a on the basis of curcumin intervention (P < 0.05). Similarly, in Wnt5a knockout mice, the promotion of muscle regeneration by curcumin was significantly attenuated. CONCLUSIONS: Curcumin can activate the Wnt5a signalling pathway and mediate the opening of Ca2+ channels to accelerate the myogenic differentiation of C2C12 cells and the repair and regeneration of injured skeletal muscle.
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Diferenciação Celular , Curcumina , Músculo Esquelético , Mioblastos , Regeneração , Proteína Wnt-5a , Animais , Proteína Wnt-5a/metabolismo , Camundongos , Diferenciação Celular/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Mioblastos/metabolismo , Mioblastos/efeitos dos fármacos , Curcumina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Canais de Cálcio/metabolismo , Masculino , Desenvolvimento Muscular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem CelularAssuntos
Fundo Gástrico , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Fundo Gástrico/cirurgia , Ligadura/métodos , Gastroscopia/métodos , Feminino , Masculino , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Pessoa de Meia-Idade , Suturas , Técnicas de SuturaRESUMO
Surface nanobubbles forming on hydrophobic surfaces in water present an exciting opportunity as potential agents of top-down and bottom-up nanopatterning. The formation and characteristics of surface nanobubbles are strongly influenced by the physical and chemical properties of the substrate. In this study, focused ion beam (FIB) milling is used for the first time to spatially control the nucleation of surface nanobubbles with 75 nm precision. The spontaneous formation of nanobubbles on alternating lines of a self-assembled monolayer (octadecyltrichlorosilane) patterned by FIB is detected by atomic force microscopy. The effect of chemical vs topographical surface heterogeneity on the formation of nanobubbles is investigated by comparing samples with OTS coating applied pre- vs post-FIB patterning. The results confirm that nanoscale FIB-based patterning can effectively control surface nanobubble position by means of chemical heterogeneity. The effect of FIB milling on nanobubble morphology and properties, including contact angle and gas oversaturation, is also reported. Molecular dynamics simulations provide further insight into the effects of FIB amorphization on surface nanobubble formation. Combined experimental and simulation investigations offer insights to guide future nanobubble-based patterning using FIB milling.
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OBJECTIVE: The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. METHODS: This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut-off value. The Kaplan-Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). RESULTS: The best cut-off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional-hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. CONCLUSION: We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.
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Inflamação , Nomogramas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Inflamação/imunologia , Idoso , Prognóstico , Neutrófilos/imunologia , Curva ROC , Estimativa de Kaplan-Meier , Linfócitos/imunologia , Monócitos/imunologia , Metástase Neoplásica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Modelos de Riscos ProporcionaisRESUMO
A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.