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As an output effector of the Hippo signaling pathway, the TEAD transcription factor and co-activator YAP play crucial functions in promoting cell proliferation and organ size. The tumor suppressor NF2 has been shown to activate LATS1/2 kinases and interplay with the Hippo pathway to suppress the YAP-TEAD complex. However, whether and how NF2 could directly regulate TEAD remains unknown. We identified a direct link and physical interaction between NF2 and TEAD4. NF2 interacted with TEAD4 through its FERM domain and C-terminal tail and decreased the protein stability of TEAD4 independently of LATS1/2 and YAP. Furthermore, NF2 inhibited TEAD4 palmitoylation and induced the cytoplasmic translocation of TEAD4, resulting in ubiquitination and dysfunction of TEAD4. Moreover, the interaction with TEAD4 is required for NF2 function to suppress cell proliferation. These findings reveal an unanticipated role of NF2 as a binding partner and inhibitor of the transcription factor TEAD, shedding light on an alternative mechanism of how NF2 functions as a tumor suppressor through the Hippo signaling cascade.
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Vía de Señalización Hippo , Neurofibromina 2 , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Factores de Transcripción de Dominio TEA , Humanos , Proliferación Celular , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Células HEK293 , Lipoilación , Neurofibromina 2/metabolismo , Neurofibromina 2/genética , Unión Proteica , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Estabilidad Proteica , Factores de Transcripción de Dominio TEA/metabolismo , Proteínas Supresoras de Tumor , UbiquitinaciónRESUMEN
Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.
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Nostoc , Rayos Ultravioleta , Humanos , Biomasa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Nostoc/metabolismo , Fotosíntesis/fisiologíaRESUMEN
Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root-soil interactions across soils with different nutrient statuses remain elusive. We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long-term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones. The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient-deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input. In conclusion, our results show that maize selects microbes at the root-soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.
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Alphaproteobacteria , Microbiota , Zea mays/microbiología , Microbiología del Suelo , Suelo/química , Rizosfera , FertilizaciónRESUMEN
Urease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency than the clinically used urease inhibitor acetohydroxamic acid. The most active inhibitor with IC50 value of 1.2 µM was over 20-fold higher potent than the positive control. Enzymatic kinetic assays showed that these novel inhibitors reversibly inhibited urease with a mixed competitive mechanism. Molecular dockings provided evidence for the observations in enzyme assays. Furthermore, these novel inhibitors were proved as drug-like compounds with very low cytotoxicity to mammalian cells and favorable water solubility. These results suggested that triazolone and oxadiazolone were promising scaffolds for the design and discovery of novel urease inhibitors, and were expected as good candidates for further drug development.
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Helicobacter pylori , Úlcera Gástrica , Animales , Ureasa , Simulación del Acoplamiento Molecular , Urea , Inhibidores Enzimáticos/farmacología , Mamíferos/metabolismoRESUMEN
Cryopreservation is a common way for long-term storage of therapeutical proteins, erythrocytes, and mammalian cells. For cryoprotection of these biosamples to keep their structural integrity and biological activities, it is essential to incorporate highly efficient cryoprotectants. Currently, permeable small molecular cryoprotectants such as glycerol and dimethyl sulfoxide dominate in cryostorage applications, but they are harmful to cells and human health. As acting in the extracellular space, membrane-impermeable macromolecular cryoprotectants, which exert remarkable membrane stabilization against cryo-injury and are easily removed post-thaw, are promising candidates with biocompatibility and feasibility. Water-soluble hydroxyl-containing polymers such as poly(vinyl alcohol) and polyol-based polymers are potent ice recrystallization inhibitors, while polyampholytes, polyzwitterions, and bio-inspired (glyco)polypeptides can significantly increase post-thaw recovery with reduced membrane damages. In this review, the synthetic macromolecular cryoprotectants are systematically summarized based on their synthesis routes, practical utilities, and cryoprotective mechanisms. It provides a valuable insight in development of highly efficient macromolecular cryoprotectants with valid ice recrystallization inhibition activity for highly efficient and safe cryopreservation of cells.
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BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.
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Parálisis de Bell , Trastorno Depresivo , Adulto , Humanos , Femenino , Masculino , Parálisis de Bell/epidemiología , Parálisis de Bell/etiología , Parálisis de Bell/psicología , Puntaje de Propensión , Estudios de Cohortes , Modelos de Riesgos ProporcionalesRESUMEN
It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.
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Enfermedad de la Arteria Coronaria , Fallo Renal Crónico , Humanos , Inhibidores de Agregación Plaquetaria , Clopidogrel , Ticagrelor , Enfermedad de la Arteria Coronaria/terapia , Ticlopidina , Aspirina , Fallo Renal Crónico/complicaciones , Diálisis Renal , Adenosina DifosfatoRESUMEN
BACKGROUND: Psoriasis, an autoimmune skin condition, affects 2%-4% of the global population, with significant prevalence among women of childbearing age. Pregnancy presents challenges in managing psoriasis due to hormonal changes and treatment safety concerns. Understanding treatment patterns in pregnant women is crucial, given limited real-world evidence. OBJECTIVES: Explore the utilization patterns of medications among pregnant women diagnosed with psoriasis within a real-world data, utilizing data sourced from a nationwide database in Taiwan. METHODS: This nationwide study utilized Taiwan's National Health Insurance (NHI) database and Birth Certificate Application. It included registered pregnant women diagnosed with psoriasis from 2005 to 2014. Medication usage was tracked three years before conception to three years after delivery. Medications were categorized based on Anatomical Therapeutic Chemical (ATC) codes, and statistical analyses were conducted using SAS software. RESULTS: A total of 30,267 pregnant women with psoriasis were studied. 11,651 (38.49%) mothers had received at least one prescription during follow-up (exposed group), and >60% had never received medication (unexposed group). Demographics and comorbidities were similar between these two groups. Topical corticosteroids were the most prescribed treatment, followed by phototherapy, with systemic drugs and biologics less common. During the study period, 11,096 women with psoriasis had used topical corticosteroids, 3,376 had used non-steroidal topical agents, 218 had used systemic agents or biologics, and 519 had received treatment with phototherapy. Medication usage declined during pregnancy, reaching its lowest in the third trimester but rebounded postpartum. CONCLUSIONS: Psoriasis medications, systemic, biological, or topical, were largely discontinued during pregnancy, sometimes up to 2 years before and extending postpartum. Research is needed to understand its impact on maternal and child health.
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BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.
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Amiodarona , Antiarrítmicos , Catarata , Humanos , Amiodarona/efectos adversos , Masculino , Femenino , Catarata/inducido químicamente , Catarata/epidemiología , Taiwán/epidemiología , Antiarrítmicos/efectos adversos , Persona de Mediana Edad , Anciano , Incidencia , Adulto , Factores de Riesgo , Modelos de Riesgos Proporcionales , Estudios de Cohortes , Propafenona/efectos adversosRESUMEN
BACKGROUND: Young men who have sex with men (YMSM) may experience high levels of sexual minority stigma (SMS) and depressive symptoms (DS) over the world and in China. However, there is a lack of studies investigating the longitudinal effects of SMS on DS of YMSM, especially focusing on YMSM and separating the between-person and within-person effects. This study aimed to fill the said gaps. METHODS: Study data were derived from a prospective cohort of 349 YMSM from central China (Wuhan, Changsha, Nanchang), the baseline survey was started in 2017 with one follow-up visit every year. SMS and DS were measured three times using valid and reliable instruments. The cross-lagged panel model (CLPM) and the random intercept CLPM (RI-CLPM) were used to examine the between-person and within-person concurrent and lagged effects, respectively. RESULTS: Findings of CLPM revealed bidirectional associations between SMS and DS over time. RI-CLPM suggested that at the between-person level, SMS was significantly associated with DS, echoing the results of CLPM. However, this reciprocal relationship has not been found at the within-person level. CONCLUSION: The associations between SMS and DS among YMSM at the population level is more significant than that at the individual level. We suggest that interventions should be against the adverse effects of cultural marginalization and systemic change the social concepts to reduce the amount of SMS in society.
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Depresión , Homosexualidad Masculina , Minorías Sexuales y de Género , Estigma Social , Humanos , Masculino , Depresión/psicología , Depresión/diagnóstico , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Minorías Sexuales y de Género/psicología , Minorías Sexuales y de Género/estadística & datos numéricos , Adulto Joven , Estudios Longitudinales , China , Estudios Prospectivos , Adolescente , AdultoRESUMEN
Atopic dermatitis (AD) is a common chronic skin inflammation. It was to screen differentially expressed genes (DEGs) and related biological functional pathways in atopic dermatitis (AD) by bioinformatics methods, and to understand the pathogenesis of AD. gene chip datasets GSE120721 and GSE32924 in the public database NCBI Gene Expression Omnibus (GEO) were adopted. Differential expression analysis between the patient group and controls was performed by applying the zero-code differential expression analysis tool GEO2R, and a few DEGs were screened. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. In addition, the STRING online database was employed to predict the potential relationship among DEGs, the protein-protein interaction network (PPI) was drawn, and the module analysis of PPI was performed using the Cytoscape plugin MCODE. 233 DEGs were screened out, including 134 up-regulated genes and 99 down-regulated genes. GO analysis suggested that these DEGs were mainly involved in biological processes (BP), cellular components (CC), and molecular function (MF). KEGG analysis displayed that these DEGs were mainly involved in NF-kappa B signaling, cell cycle, T cell receptor signaling, and other pathways. PPI analysis indicated that there were complex interactions among DEGs, and module analysis further revealed the important roles of DEGs in regulating immune response, inflammatory response, and skin barrier function. The above findings provide a valuable reference for the development of new treatment options.
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Dermatitis Atópica , Perfilación de la Expresión Génica , Humanos , Perfilación de la Expresión Génica/métodos , Dermatitis Atópica/genética , Mapas de Interacción de Proteínas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Biología Computacional/métodosRESUMEN
Gear mechanism transmits the motion and power of parallel axes, intersecting axes and staggered axes, which has been widely employed in production and life. Gear-type mobile mechanism is a type of robot that can achieve motion through gear transmission. Due to its unique motion mode, it can handle various tasks in certain unconventional environments, such as particularly steep surfaces. Cylindrical gear, bevel gear and non-cylindrical gear are taken as the main parts of the mechanism to form a novel research series, respectively. The models of gear-type mobile mechanism are established in this paper, and the degrees of freedom of the mechanism are briefly calculated based on the screw theory. Simultaneously, the influence of centroid trajectory on motion stability is discussed to solve the possible problem that opposite rotation occur during the movement. Furthermore, the trajectory model of zero moment point is calculated considering the motion of the gear-type mobile mechanism. After that, the simulation and experimental analysis of its motion capability show that the gear-type mobile mechanism has excellent characteristics in stability, flexibility and continuity.
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Objective: The increasing identification of pulmonary nodules has led to a growing emphasis on segmentectomy. Nevertheless, the surgical process for segmentectomy is complex and optimizing segmentectomy is a critical clinical concern. This study aimed to evaluate the safety and short- and long-term efficacy of V6-preserving superior segmentectomy. Methods: We performed a retrospective analysis of patients who underwent thoracoscopic superior segmentectomy at our hospital between January 2019 and June 2020. Eligible patients were categorized into an V6 vein-preserving segmentectomy (VVPS) group and a Non V6 vein-preserving segmentectomy (NVVPS) group depending on the preservation of V6. Primary outcome measures encompassed the evaluation of surgical safety (surgical margins, 3-year overall survival, and disease-free survival), whereas secondary measures included postoperative complication rates, operative time, estimated intraoperative blood loss, length of hospital stay, and associated costs. Results: The analysis included a final cohort of 78 patients. In the NVVPS group (n = 43), 95.3 % of patients exceeded the tumor diameter, and no positive surgical margins were observed. The 3-year overall survival (OS) and disease-free survival (DFS) rates for the NVVPS group were 95.3 %, with no significant differences in OS (p = 0.572) and DFS (P = 0.800) compared with the VVPS group. Additionally, the median total hospitalization cost for the NVVPS group was 41,400 RMB (IQR, 38,800-43,400), which was significantly lower than that of the VVPS group, showing statistical significance (P < 0.05). No statistically significant differences were observed in the incidence of postoperative complications and length of stay between the two groups (P > 0.05). Conclusion: V6-preserving superior segmentectomy is a secure and optimized surgical alternative. Its streamlined procedure facilitates easier adoption in primary healthcare facilities, rendering it a superior choice for superior segmentectomy.
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BACKGROUND: Hip dysplasia is one of the most prevalent disorders in children and one of the three primary congenital orthopedic deformities. Although there are numerous existing methods (e.g., CT, MRI and arthrography) for early identification of hip dysplasia, their diagnostic criteria differ widely. It is critical to establish a safe, accurate, and reliable way for early diagnosis and treatment of hip dysplasia. OBJECTIVE: This study aimed to analyze the diagnostic efficacy of high-frequency ultrasound (HFU) for congenital developmental hip dysplasia and hip dislocation and to provide a reference for the early diagnosis of congenital hip dysplasia in the future. METHODS: A total of 104 infants and children suspected of having congenital hip dislocation or developmental hip dysplasia admitted to our hospital from April 2019 to August 2022 were enrolled as study subjects. All the infants and children were subjected to HFU and X-ray examination in our hospital. The diagnostic efficacy of HFU for congenital hip dysplasia was observed using X-ray as the gold standard. RESULTS: HFU confirmed 79 cases of congenital hip dysplasia, while X-ray confirmed 71 cases. The sensitivity and specificity of HFU were 77.42% and 83.33%, respectively, in the diagnosis of congenital developmental hip dysplasia, 76.47% and 96.55% in the diagnosis of congenital hip dislocation, and 77.22% and 60% in the diagnosis of congenital hip abnormality, which is very close to the gold standard. According to statistics on infants and children, the majority of patients were girls, and the left joint was more likely to be affected. CONCLUSION: HFU has excellent diagnostic efficiency for congenital developmental hip dysplasia and hip dislocation, which can be considered an early assessment method for congenital hip dysplasia in the future.
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Sustainable strategies to improve the water resistance of cellulose paper are actively sought. In this work, polymeric microspheres (PMs), prepared through emulsion polymerization of cellulose nanofibers stabilized rubber seed oil-derived monomer, were investigated as coatings on corrugated medium paper (CMP). After infiltrating porous paper with PMs, the water-resistant corrugated papers (WRCPn) with enhanced mechanical properties were obtained. When 30 wt% PMs were introduced, WRCP30 turned out to be highly compacted with an increased water contact angle of 106.3° and a low water vapor transmission rate of 81 g/(m2 d) at 23 °C. Meanwhile, the tensile strength of WRCP30 increased to 22.2 MPa, a 4-fold increase from CMP. When tested in a well-hydrated state, 71% of its mechanical strength in the dry state was maintained. Even with a low content of 10 wt% PMs, WRCP10 also exhibited stable tensile strength and water wettability during the cyclic soaking-drying process. Thus, the plant oil based sustainable emulsion polymers provide a convenient route for enhancing the overall performance of cellulose paper.
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Celulosa , Microesferas , Aceites de Plantas , Resistencia a la Tracción , Agua , Celulosa/química , Agua/química , Aceites de Plantas/química , Papel , Humectabilidad , Polímeros/química , Emulsiones/química , Porosidad , Nanofibras/químicaRESUMEN
The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.
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Técnicas Biosensibles , Melanoma , Humanos , Técnicas Electroquímicas , Reproducibilidad de los Resultados , Melanoma/diagnóstico , Péptidos/química , Límite de DetecciónRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. PURPOSE: This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. METHODS: Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. RESULTS: Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tertbutylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. CONCLUSIONS: Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.
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Bufanólidos , Neoplasias Colorrectales , Neoplasias Pulmonares , Animales , Ratones , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Colorrectales/patología , Línea Celular Tumoral , Bufanólidos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Transición Epitelial-Mesenquimal , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Metástasis de la NeoplasiaRESUMEN
Developing large-scale hydrogels with high tensile strength and robust mechanical properties is an intricate challenge of great industrial significance. In this study, we demonstrate an efficient method for producing nanocomposite hydrogels with extraordinary mechanical properties. Our approach involves a two-step process: an initial stage of pre-cross-linking boron nitride (BN)-enriched pre-gel sodium alginate, followed by cross-linking with metal ions. In stark contrast to conventional sodium alginate hydrogels (SA), our newly formulated 'BS hydrogel' exhibited an impressive tensile strength exceeding 41 MPa and improved thermal resistance. Moreover, the reconstituted BS hydrogel exhibited tensile strengths ranging from 47 to 96 MPa and elastic moduli ranging from 199 to 1184 MPa, depending on the cross-linking metal ions. These findings indicate the multifaceted potential of the BS hydrogel, which is poised to revolutionize many applications and represents a significant step forward in hydrogel technology for industrial applications.
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Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.