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OBJECTIVE: The specific breast milk-derived metabolites that mediate host-microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. DESIGN: We enrolled 250 mother-infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings. RESULTS: The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, 'GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis'). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-γ. CONCLUSIONS: This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.
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Skin, characterized by its distinctive gradient structure and interwoven fibers, possesses remarkable mechanical properties and highly sensitive attributes, enabling it to detect an extensive range of stimuli. Inspired by these inherent qualities, a pioneering approach involving the crosslinking of macromolecules through in situ electron beam irradiation (EBI) is proposed to fabricate gradient ionogels. Such a design offers remarkable mechanical properties, including excellent tensile properties (>1000%), exceptional toughness (100 MJ m-3), fatigue resistance, a broad temperature range (-65-200°C), and a distinctive gradient modulus change. Moreover, the ionogel sensor exhibits an ultra-fast response time (60 ms) comparable to skin, an incredibly low detection limit (1 kPa), and an exceptionally wide detection range (1 kPa-1 MPa). The exceptional gradient ionogel material holds tremendous promise for applications in the field of smart sensors, presenting a distinct strategy for fabricating flexible gradient materials.
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BACKGROUND: The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients. METHODS: This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C). RESULTS: Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P < 0.05). Furthermore, AIP was independently associated with LVMIh2.7 according to multivariate linear regression model (ß = 0.125, P = 0.001). Notably, AIP remained independently associated with an elevated risk of LVH [odds ratio (OR) = 1.317 per 1 standard deviation (SD) increment, 95% confidence interval (CI): 1.058 - 1.639, P = 0.014) and concentric LVH (OR = 1.545 per 1 SD increment, 95% CI: 1.173 - 2.035, P = 0.002) after fully adjusting for all confounding risk factors by multivariate logistic regression analyses. CONCLUSIONS: AIP was independently associated with an increased risk of LVH and concentric LVH in OSA patients. Therefore, AIP, as a practical and cost-effective test, might be useful in monitoring hypertrophic remodeling of the heart and improving CVDs risk stratification in clinical management of OSA.
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Ecocardiografía , Hipertrofia Ventricular Izquierda , Apnea Obstructiva del Sueño , Humanos , Masculino , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones , Femenino , Persona de Mediana Edad , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Estudios Transversales , Estudios Retrospectivos , Anciano , Aterosclerosis/sangre , Triglicéridos/sangre , Adulto , HDL-Colesterol/sangre , Resistencia a la Insulina , Factores de RiesgoRESUMEN
Mother-child cohesion, reflecting the emotional connection between mothers and children, is a protective factor for individuals' mental health. The Modified Operations Triad Model suggests that children and mothers hold either congruent or incongruent views of their perceived cohesion, which reflects family functioning and is an indication of future mental health outcomes for family members. Despite increasing research on the impact of (in)congruence in perceived family functioning on children's mental health, few studies concurrently address the mental health of both mothers and children, overlooking their interdependence. This longitudinal study with multi-informant reports explored the long-term and developmental effects of (in)congruence in perceived mother-child cohesion on informants' depressive symptoms. A total of 577 families participated at the first time point, comprising 577 children (52.34% girls, Mage = 10.11 years) and 577 mothers (Mage = 37.32 years). The Dyadic Response Surface Analysis revealed that mother-child congruence at high levels of cohesion (versus low levels) predicted fewer depressive symptoms in mothers and children after three and nine months, as well as decreased depressive symptoms over nine months. Children who reported higher levels of cohesion than their mothers experienced fewer depressive symptoms after three months. Mothers with higher levels of cohesion than their children reported fewer depressive symptoms after three months. The current findings emphasize the importance of identifying and resolving discrepancies in perceived mother-child cohesion between mothers and children to promote a healthy family environment.
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Depresión , Madres , Femenino , Humanos , Niño , Adulto , Masculino , Depresión/psicología , Estudios Longitudinales , Madres/psicología , Salud Mental , Relaciones Madre-HijoRESUMEN
Accurate quantification and dynamic expression profiling of mitochondrial RNA (mtRNA for short) are critical for illustrating their cellular functions. However, there lack methods for precise detection of mtRNA in situ due to the delivery restrictions and complicated cellular interferences. Herein, a dual-color imaging system featured with signal amplification and normalization capability for quantitative analysis of specific mtRNA is established. As a proof-of-concept example, an enzyme-free hairpin DNA cascade amplifier fine-tailored to specifically recognize mtRNA encoding NADH dehydrogenase subunit 6 (ND6) is employed as the signal output module and integrated into the biodegradable mitochondria-targeting black phosphorus nanosheet (BP-PEI-TPP) to monitor spatial-temporal dynamics of ND6 mtRNA. An internal reference module targeting ß-actin mRNA is sent to the cytoplasm via BP-PEI for signal normalization, facilitating mtRNA quantification inside living cells with a degree of specificity and sensitivity as high as reverse transcription-quantitative polymerase chain reaction (RT-qPCR). With negligible cytotoxicity, this noninvasive "RT-qPCR mimic" can accurately indicate target mtRNA levels across different cells, providing a new strategy for precise analysis of subcellular RNAs in living systems.
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Mitocondrias , ARN , Humanos , ARN Mitocondrial/metabolismo , Mitocondrias/metabolismo , ARN Mensajero/metabolismo , Citoplasma/metabolismoRESUMEN
Developing a new universal strategy to design all organic ferromagnets or multiferroics with satisfactory properties always remains challenging. In this work, ternary charge transfer crystals are fabricated to realize organic multiferroic magnetoelectric coupling effect. Through incorporating the third component into binary crystals, a dimerization between neighbor donor and acceptor is induced to form a lattice symmetry breaking, where a nonpolar to polar phase transition is ensuing to lead to a dipolar polarization. Magnetic field can effectively tune the dipolar polarization to present a magnetoelectric coupling effect. Moreover, the introduction of the third component can result in a rearrangement in molecular configuration to modify the electron-phonon interaction. As a result, anisotropic magnetism is observed due to anisotropic electron-phonon coupling in ternary crystals. Overall, this study forecasts that incorporating an appropriate third component is a potential method for designing all organic multiferroics.
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BACKGROUND: This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). METHODS: The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. RESULTS: Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22-2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02-1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12-6.64], P < 0.001), and free androgen index (FAI) (OR, 1.37 [95% CI, 1.16-1.64], P < 0.001) were associated with a higher possibility of no response to 2.5 mg LET. CONCLUSIONS: PCOS patients with an increased LH/FSH ratio, AMH, FAI, and late menarche may need an increased dosage of LET for a treatment response, which could be helpful in designing a personalized treatment strategy.
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Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Letrozol/uso terapéutico , Síndrome del Ovario Poliquístico/complicaciones , Estudios Retrospectivos , Fármacos para la Fertilidad Femenina/uso terapéutico , Hormona Folículo Estimulante , Inducción de la Ovulación , Hormona LuteinizanteRESUMEN
BACKGROUND: Diabetic cardiomyopathy results in cardiac structural and functional abnormalities. Previous studies have demonstrated that inhibiting the RhoA/ROCK signalling pathway increases the injury resistance of cardiomyocytes. The early detection of cardiac structural and functional alterations may facilitate an improved understanding of the pathophysiologic progress and guide therapy. This study aimed to identify the optimal diagnostic measures for the subtle early alterations of cardiac dysfunction in type 2 diabetes mellitus (T2DM) rats. METHODS: Twenty-four rat models were divided into four groups and received treatments for 4 weeks: the CON group (control rats), the DM group (T2DM rats), the DMF group (T2DM rats receiving fasudil) and the CONF group (control rats receiving fasudil) group. Left ventricular (LV) structure was quantified by histological staining and transmission electron microscopy. LV function and myocardial deformation were assessed by high-frequency echocardiography. RESULTS: Treatment with fasudil, a ROCK inhibitor, significantly protected against diabetes-induced myocardial hypertrophy, fibrosis and mitochondrial dysfunction. Impaired LV performance was found in T2DM rats, as evidenced by significant reductions in the ejection fraction (EF), fractional shortening (FS) and the mitral valve (MV) E/A ratio (which decreased 26%, 34% and 20%, respectively). Fasudil failed to improve the conventional ultrasonic parameters in T2DM rats, but the myocardial deformation measured by speckle-tracking echocardiography (STE) were significantly improved (global circumferential strain, GCS: P = 0.003; GCS rate, GCSR: P = 0.021). When receiver operating characteristic (ROC) curves were used in combination with linear regression analysis, STE parameters were found to be characterized by both optimal prediction of cardiac damage [AUC (95% CI): fractional area change, FAC: 0.927 (0.744, 0.993); GCS: 0.819 (0.610, 0.945); GCSR: 0.899 (0.707, 0.984)] and stronger correlations with cardiac fibrosis (FAC: r = -0.825; GCS: r = 0.772; GCSR: r = 0.829) than conventional parameters. CONCLUSION: The results suggest that STE parameters are more sensitive and specific than conventional parameters in predicting the subtle cardiac functional changes that occur in the early stage, providing new insight into the management of diabetic cardiomyopathy.
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Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Disfunción Ventricular Izquierda , Ratas , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/complicaciones , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/etiología , Ecocardiografía/métodos , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: The 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents. METHODS: The data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale. RESULTS: A two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance. CONCLUSIONS: The factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.
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Depresión , Pueblos del Este de Asia , Adolescente , Femenino , Humanos , Masculino , Depresión/diagnóstico , Emociones , Análisis Factorial , Psicometría , Reproducibilidad de los Resultados , NiñoRESUMEN
The response of crystal structure to external stimuli provides potential applications in the areas of detection, diagnosis, and repair. In this work, we fabricate two allotropic organic cocrystals, with different space groups and lattice parameters, with identical donor and acceptor molecules inside them. Under external stimuli, lattice vibration and electron-phonon coupling present pronounced differences in these two types of crystals, where different strengths of spin polarizations are observed. Furthermore, due to pronounced differences in coupling between lattice and spin inside the allotropic charge transfer crystals, the magnetic field presents a discrepant tunability on both transmission and fluorescence lifetimes. Through decreasing temperature or applying external electric field, the electron-phonon coupling coefficient presents a decreasing tendency, which will affect the dipole and dielectric constant in the allotropic crystals differently.
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Electrones , Fonones , Electricidad , Campos Magnéticos , VibraciónRESUMEN
This work was developed to investigate the activation of silent information regulator 1 (SIRT1) to regulate hypoxia-induced oxidative stress in cardiomyocytes through the PI3K/MTOR signaling pathway. For this purpose, 30 SD healthy rats were selected, and 10 of them were randomly selected as the control group. The remaining 20 rats were established as acute myocardial infarction model rats, and randomly divided into model group and activated SIRT1 group. Interventions were performed on rats in each of the 3 groups. ROS staining, inflammatory factors [IL-6, IL-1ß levels], H9c2 cell viability, Caspase3 and Caspase8 activity, antioxidant enzyme indexes [SOD, CAT, MDA levels], SIRT1, PI3K, MTOR, HIF-1α, HO-1, GLUT1 mRNA expression were compared between groups. Results showed that IL-6 and IL-1ß levels were abnormally elevated in the model group compared with the control group (P<0.05). IL-6 and IL-1ß levels decreased in the activated SIRT1 group compared with the model group (P<0. 05). H9c2 cell viability decreased and Caspase3 and Caspase8 activities increased in the model group compared with the control group(P <0.05). H9c2 cell viability increased and Caspase3 and Caspase8 activities decreased in the activated SIRT1 group compared with the model group (P<0.05). SOD and CAT levels were abnormally decreased and MDA levels were abnormally increased in the model group compared with the control group (P<0.05). SOD and CAT levels were abnormally increased and MDA levels were decreased in the activated SIRT1 group compared with the model group (P<0.05). PI3K and SIRT1 expression decreased and MTOR expression increased in the model group compared with the control group (P < 0. 05). PI3K and SIRT1 expression increased and MTOR expression decreased in the activated SIRT1 group compared with the model group(P<0.05). The expression of HIF-1α, HO-1 and GLUT1 mRNA increased in the model group compared with the control group, and the difference was statistically significant (P <0.05). The expression of HIF-1α, HO-1, and GLUT1 mRNA decreased in the activated SIRT1 group compared with the model group, and the difference was statistically significant (P<0.05). It was concluded that the activation of SIRT1 can regulate PI3K/MTOR signaling pathway, thus reducing hypoxia-induced oxidative stress in cardiomyocytes, inflammatory conditions and enhancing cardiomyocyte viability, with better intervention effects.
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Miocitos Cardíacos , Fosfatidilinositol 3-Quinasas , Animales , Transportador de Glucosa de Tipo 1/metabolismo , Hipoxia , Interleucina-6/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Mensajero/metabolismo , Ratas , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismo , Superóxido Dismutasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Previous studies have demonstrated the correlations between cyberbullying victimization and disordered eating behaviors in adolescents, however, limited attention has been paid to the long-term effects and underlying mechanisms, and studies focused on young adults are scarce. This study explored the association between cyberbullying victimization and disordered eating behaviors and the underlying mechanisms in a sample of young adults using a longitudinal design. A total of 955 Chinese young adults completed the Cyber Victim Subscale of the Cyber Victim and Bullying Scale, the Self-surveillance Subscale of the Objectified Body Consciousness Scale, the Self-compassion Scale-Short Form, and the Dutch Eating Behaviors Questionnaire three times with a 3-months interval. The results indicated that cyberbullying victimization was positively correlated with emotional eating and external eating after six months, but not with restrained eating. Moreover, self-compassion and self-objectification mediated the associations between cyberbullying victimization and the three kinds of disordered eating behaviors, however, in different ways. In the associations of cyberbullying victimization with restrained eating and external eating, the independent mediating effect of self-objectification and the serial mediating effect were significant, while in the association between cyberbullying victimization and emotional eating, only the independent mediating effect of self-compassion was significant. The findings indicated that the relations between cyberbullying with different kinds of disordered eating behaviors might have different mediation mechanisms, which sheds light on the prevention and intervention for disordered eating behaviors associated with cyberbullying in the future.
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Acoso Escolar , Víctimas de Crimen , Ciberacoso , Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Víctimas de Crimen/psicología , Ciberacoso/psicología , Humanos , Autocompasión , Adulto JovenRESUMEN
Accumulating evidence has showed the possibility of using NK1R antagonists for the treatment of chronic pruritus. However, the benefit and risk profile of NK1R antagonists-serlopitant and aprepitant for the treatment of pruritus remains unclear. To assess the efficacy and safety of NK1R antagonists-serlopitant and aprepitant in patients with pruritus based on analysis of clinical trials. The current systematic review and meta-analysis was performed according to PRISMA guidelines. A total of 10 randomized clinical trials including 631 patients were enrolled. Four randomized controlled trials investigated the comparative treatment effect of serlopitant on pruritus. Our results showed that serlopitant had reasonable anti-pruritic effectiveness in patients, with mild toxicities. The overall proportion of 4-point improvement of NRS and VAS in serlopitant-treatment group were both significantly higher relative to placebo group (OR 2.345, 95%CI 1.557 to 3.531, P < .001; OR 3.308, 95% CI 1.949 to 5.616, P < .001). Serlopitant treatment was also found to be associated with a significant reduction in NRS score as compared with placebo (SMD -0.381, 95%CI -0.599 to -0.164, P = .001). Six clinical trials reported the treatment effect of aprepitant on pruritus. The meta-analysis result of fixed-effect model showed that there was no significant difference between aprepitant and controlled treatment in terms of improved pruritus VAS score (SMD -0.088, 95%CI -0.384 to 0.207, P = .558). There is promising high-quality evidence regarding the efficacy of serlopitant on pruritus. More large-sample randomized controlled trials with appropriate treatment regimen are urgently needed to further evaluate the effectiveness of aprepitant in pruritus.
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Antagonistas del Receptor de Neuroquinina-1 , Prurito , Humanos , Antagonistas del Receptor de Neuroquinina-1/efectos adversos , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
An ultrasensitive label-free electrochemical immunosensor was fabricated for quantitative detection of Lactobacillus rhamnosus GG (LGG). The N/O co-doped three-dimensional hierarchical porous graphitic (THPG) carbon was synthesized by a one-step synthesis of polyaniline hydrogel, and followed by simple carbonization and chemical activation procedures. Because of the unique structure design, the obtained THPG carbon networks possess an ultra-large specific surface area of 4859 m2 g-1 along with a class of highly graphitic carbons. The results offer an enormous surface area and excellent electrical conductivity for label-free electrochemical immunosensing of probiotic L. rhamnosus strain. Under optimal conditions, the immunosensor showed a good linear relationship between peak current and concentration of LGG (R2 = 0.9976), with a detection limit of 2 CFU mL-1. Furthermore, this label-free immunosensor also shows good specificity, long-term stability, and reliability, and could be applied to detect probiotic LGG in dairy products and drinks with satisfactory results. The present protocol was shown to be quite promising for practical screening and functional evaluation of probiotic products containing LGG. A ultrasensitive label-free electrochemical immunosensor based on THPG carbon was fabricated for detection of Lactobacillus rhamnosus GG.
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Carga Bacteriana/métodos , Grafito/química , Inmunoensayo/métodos , Lacticaseibacillus rhamnosus/aislamiento & purificación , Probióticos/análisis , Anticuerpos Inmovilizados/inmunología , Productos Lácteos/análisis , Productos Lácteos/microbiología , Técnicas Electroquímicas , Lacticaseibacillus rhamnosus/inmunología , Límite de Detección , Nitrógeno/química , Oxígeno/química , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known. METHODS: The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model. RESULTS: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway. CONCLUSIONS: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.
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Precise and rapid sensing of Fe(III) under concerned facile conditions is important in environmental monitoring. Herein, a facile and label-free ratiometric sensor is constructed for selective determination of Fe(III) ions by coupling second-order scattering (SOS) and fluorescence. We were synthesized fluorescent N, S-doped carbon dots (N/S-CDs) via facile one-step hydrothermal treatment with an intensive fluorescence and a weak SOS signal and high quantum yield (32%). The fluorescence of N/S-CDs was quenched whereas the intensity of SOS was relatively increased by Fe(III) ions due to aggregation-induced fluorescence quenching or enhancement. Based on this effect, a novel fluorescent ratiometric probe with the combined fluorescence and SOS is proposed for the sensing of Fe(III) ions, and with the detection limit of 83 nM and linear range of 0.1-10 µM and 10-40 µM, respectively.
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Carbono/química , Compuestos Férricos/análisis , Colorantes Fluorescentes/química , Luz , Puntos Cuánticos/química , Contaminantes Químicos del Agua/análisis , Iones/análisis , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
2,3-Disubstituted benzofurans were synthesized from acrolein dimer and 1,3-dicarbonyl compounds by using N-bromosuccinimide as an oxidizing agent. The method was used to synthesize two commercial drug molecules, benzbromarone and amiodarone. The proposed mechanism of the reaction involves a N-bromosuccinimide (NBS)-assisted autotandem catalysis with Lewis acid catalyst. To proof the proposed mechanism, an intermediate was isolated successfully, which can be converted to 4,5,6,7-tetrahydrobenzofurans.
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1,2,4-Trisubstituted pyrroles were synthesized from enolizable aliphatic aldehydes and primary aliphatic amines by using iodine as the dual Lewis acid/mild oxidant. In the presence of 3.0 equiv of TBHP, enolizable α,ß-unsaturated aldehyde, for example, cocal reacted with aromatic primary amines to form C2-iodized N-arylpyrroles. An acetal-containing pyrrole was successfully prepared from 4-aminobutyraldehyde diethyl acetal, which can be converted easily to 5,6,7,8-tetrahydroindolizine derivatives.
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A universal strategy is developed to construct metal-organic framework (MOF)-based superhydrophobic/superoleophilic materials by the reaction of activated MOFs and octadecylamine. In particular, S-MIL-101(Cr) composite can efficiently separate chloroform, toluene, petroleum ether, and n-hexane from water with excellent oil-water separation performance, with potential application in the environmental field.
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A unique 3D framework containing three different types of nanoscale polyhedron cages was constructed by incorporating dinuclear [M2(µ2-OH)(COO)4] (M = Co, Ni) secondary building units and pyridyl-carboxylic-acid-supported tetracarboxylates. The assembled complexes possess isolated bifunctional single-site Lewis acid and Brønsted acid and can be used as highly efficient heterogeneous catalysts for the solvent-free Biginelli reaction with a high turnover frequency value of 338.4 h-1. Interestingly, a variety of 3,4-dihydropyrimidin-2(1 H)-ones have been obtained in high yields and short times.