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Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.
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The shrinkage and collapse of wood cell walls during carbonization make it challenging to control the size and shape of carbonized wood (CW) through pre- or postprocessing (e.g., sawing, cutting, and milling). Herein, a shape-adaptive MXene shell (MS) is created on the surface of the wood cell walls. The MS limits the deformation of wood cell walls by spatial confinement and traction effects, which is supported by the inherent dimensional stability of the MS and the formation of new C-O-Ti covalent bonds between the wood cell wall and MS. Consequently, the volumetric shrinkage ratio of CW encapsulated by the MS (CW-MS) is significantly reduced from 54.8% for CW to 2.6% for CW-MS even at 800 °C. The harnessing of this collapse enables the production of CW-MS with prolonged stability and high electric conductivity (384 S m-1). These properties make CW-MS suitable for energy storage devices with various designed shapes, matching the increasingly compact and complex structures of electronic devices.
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Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.
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Camptotecina/análogos & derivados , Neoplasias Colorretais , Inibidores da Topoisomerase I , Humanos , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Neoplasias Colorretais/terapia , Citosol , Microambiente TumoralRESUMO
pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.
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Peptídeos , Concentração de Íons de Hidrogênio , Peptídeos/química , Conformação Proteica em Folha beta , Ensaios de Triagem em Larga Escala/métodos , Nanofibras/química , Interações Hidrofóbicas e Hidrofílicas , Benzotiazóis/químicaRESUMO
Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.
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Background: Side branch (SB) occlusion after main vessel stenting is the main complication in treating coronary bifurcation lesions by provisional stenting. The Jailed Wire Technique (JWT), recommended by the European Bifurcation Club, is a standard technique to deal with this issue. The Jailed Balloon Technique (JBT) has been found to be more effective than the JWT in clinical practice by some interventionists, but it has not been widely accepted. In this meta-analysis, we compared the efficacy and safety of JBT and JWT. Methods: The literature comparing JBT and JWT was systematically reviewed. Stata/MP 17.0 was used to perform a meta-analysis. The primary endpoints were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). The secondary endpoints were SB occlusion and SB dissection. Aggregated odds ratios and 95% confidence intervals were calculated. A sensitivity analysis was conducted if I 2 was > 50% or p < 0.01. Results: Thirteen studies involving 1789 patients were enrolled. JBT was found to have a significantly lower incidence of MACE, SB occlusion and dissection. The incidence of cardiac death, MI and TLR were also lower in the JBT group, though the differences were not significant. Conclusions: JBT prevents SB occlusion more effectively and does not increase immediate or long-term complications. JBT, or its modified versions, can be used to treat SBs with a high risk of occlusion.
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PURPOSE: This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy. RESULTS: In this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD. CONCLUSION: Integrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.
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Neoplasias da Mama , Radiodermite , Radioterapia de Intensidade Modulada , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Radiodermite/etiologia , Radiodermite/diagnóstico por imagem , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Idoso , Adulto , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Dosagem Radioterapêutica , Inteligência Artificial , RadiômicaRESUMO
Accelerating the repair of a bone defect is crucial clinically due to the increased prevalence of trauma, tumor, and infections in bone. Studies have found that excess acute and chronic inflammation attenuate osteogenic differentiation of BMSCs (bone marrow mesenchymal stem cells). Moreover, TNF-α and NF-κB could inhibit osteoblasts differentiation of BMSCs and promote osteoclastogenesis via multiple mechanisms, such as increasing osteoclast precursor cells and acting synergistically with cell cytokines. However, melatonin could inhibit the expression of TNFα/NF-κB and promote bone formation by activating the Wnt/ß-catenin signaling pathway. However, there has been no evidence regarding the effect of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. This study aimed to investigate the role of melatonin on TNFα/NF-κB-inhibited osteoblastogenesis and bone formation. Micro-CT, high-throughput screening, overexpression, and other methods were used, and we found that the number of osteoblasts was elevated with melatonin treatment. Additionally, TNFα/NF-κB signaling was inhibited, while miR-335-5p expression increased markedly following treatment with melatonin. Furthermore, miR-335-5p negatively regulated TNFα/NF-κB signaling, while miR-335-5p inhibitor ameliorated the effects of melatonin on TNFα/NF-κB. In conclusion, melatonin facilitates osteogenesis in bone defect healing by enhancing miR-335-5p expression and inhibiting the TNFα/NF-κB pathway.
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Melatonina , MicroRNAs , NF-kappa B/metabolismo , Osteogênese , Fator de Necrose Tumoral alfa/metabolismo , Melatonina/farmacologia , MicroRNAs/metabolismo , Diferenciação Celular , Via de Sinalização Wnt , Células CultivadasRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.
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Metabolismo dos Lipídeos , Fármacos Neuroprotetores , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Homeostase/efeitos dos fármacos , Poríferos/química , Camundongos , Camundongos Endogâmicos C57BL , Autofagia/efeitos dos fármacos , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Policetídeos/farmacologia , HumanosRESUMO
A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730T, was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 â), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730T showed the highest similarity to Solibacillus isronensis JCM 13838T (96.2 %), followed by Solibacillus silvestris DSM 12223T (96.0 %) and Solibacillus kalamii ISSFR-015T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730T was menaquinone 7 (MK-7). The major fatty acids were iso-C15:0 and C16:1ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730T and the reference strain S. isronensis JCM 13838T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730T (= NBRC 116268T = CGMCC 1.60169T).
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Bactérias , Fosfolipídeos , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , China , Bactérias/genética , SoloRESUMO
Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.
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Berberina , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Berberina/análogos & derivados , Estudos de Casos e Controles , Coptis chinensis , Neurônios Dopaminérgicos/metabolismo , Mutação , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , RizomaRESUMO
PURPOSE: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout. METHODS: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening. RESULTS: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG. CONCLUSION: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.
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Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Glândulas Tarsais/diagnóstico por imagem , Disfunção da Glândula Tarsal/diagnóstico , Disfunção da Glândula Tarsal/terapia , Estudos Retrospectivos , Lágrimas , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologiaRESUMO
BACKGROUND: The newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. METHODS: We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. RESULTS: In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. CONCLUSIONS: This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.
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Inflamação , Inquéritos Nutricionais , Osteoartrite , Humanos , Masculino , Feminino , Osteoartrite/mortalidade , Pessoa de Meia-Idade , Idoso , Inflamação/mortalidade , Adulto , Causas de Morte , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: While the impact of telephone follow-up (TFU) for older emergency department (ED) patients is controversial, its effects on the Asian population remain uncertain. In this study, we evaluated the effectiveness of a novel computer assisted TFU model specifically for this demographic. METHODS: At a Taiwanese tertiary medical center, we developed a TFU protocol that included a referral and case management system within the ED hospital information system. We provided TFU to older discharged patients between April 1, 2021, and May 31, 2021. We compared this cohort with a non-TFU cohort of older ED patients and analyzed demographic characteristics and post-ED discharge outcomes. RESULTS: The TFU model was successfully implemented, with 395 patients receiving TFU and 191 without TFU. TFU patients (median age: 76 years, male proportion: 48.9%) differed from non-TFU patients (median age: 74 years, male proportion: 43.5%). Compared with the non-TFU cohort, the multivariate logistic regression analysis revealed that the TFU cohort had a lower total medical expenditure < 1 month (adjusted odds ratio [AOR]: 0.32; 95% CI: 0.21 - 0.47 for amounts exceeding 5,000 New Taiwan Dollars), and higher satisfaction (AOR: 2.80; 95% CI: 1.46 - 5.36 for scores > 3 on a five-point Likert Scale). However, the TFU cohort also had a higher risk of hospitalization < 1 month (AOR: 2.50; 95% CI: 1.31 - 4.77) compared to the non-TFU cohort. CONCLUSION: Computer-assisted TFU appears promising. Further research involving a larger number of patients and validation in other hospitals is necessary to bolster the evidence and extend the findings to a broader context.
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Serviço Hospitalar de Emergência , Alta do Paciente , Telefone , Humanos , Masculino , Feminino , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Taiwan , Idoso de 80 Anos ou mais , Povo Asiático , SeguimentosRESUMO
INTRODUCTION: Using the Five Cs model of positive youth development (PYD), this study aimed to provide a socio-structural and cultural understanding of PYD in Indigenous Tayal youth by examining the specificity in the development of Five Cs (Competence, Confidence, Character, Caring, and Connection) between Tayal and Han youth in Taiwan. METHODS: A sample of 847 Tayal and Han adolescents (43.8% Tayal, 47.9% girls, Mage = 14.83, SD = 0.50) were drawn from a larger study (September 2014 to August 2017). Adolescent participants completed questionnaires asking about their Five Cs, contribution behavior, and depressive symptomatology. RESULTS: Measurement invariance was conducted to explore specificity between Tayal and Han youth's Five Cs performance. A bi-factor Five Cs model was identified and partial metric and partial scalar measurement invariance was established between the two samples. Across both groups an overarching PYD factor, which was associated with increased contribution and lower depressive symptomatology, was identified. Specificity was observed in the Tayal sample, particularly relating to indicators of Competence, Character, Caring, and Connection. CONCLUSION: The findings of this study provide a sociocultural-informed lens regarding the specificity of development in Tayal youth. Character, Caring, and Connection appear to contribute significantly more to the overall PYD for Tayal adolescents than their Han peers. Findings relating to Competence suggest that the educational environment may not be aligned with the learning style of Tayal youth. This study has policy and practical implications for Tayal youth, and can further help inform program development in Taiwan and internationally.
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The interaction between diverse nanoarchitectured fullerenes and cells is crucial for biomedical applications. Here, we detailed the preparation of hydrophilic self-assembled fullerenes by the liquid-liquid interfacial precipitation (LLIP) method and hydrophilic coating of the materials as a possible vascularization strategy. The interactions of vascular endothelial cells (ECs) with hydrophilic fullerene nanotubes (FNT-P) and hydrophilic fullerene nanowhiskers (FNW-P) were investigated. The average length and diameter of FNT-P were 16 ± 2 µm and 3.4 ± 0.4 µm (i.e. aspect ratios of 4.6), respectively. The average length and diameter of FNW-P were 65 ± 8 µm and 1.2 ± 0.2 µm (i.e. aspect ratios of 53.9), respectively. For two-dimensional (2D) culture after 7 days, the ECs remained viable and proliferated up to ~ 420% and ~ 400% with FNT-P and FNW-P of 50 µg/mL, respectively. Furthermore, an optimized chitosan-based self-healing hydrogel with a modulus of ~400 Pa was developed and used to incorporate self-assembled fullerenes as in vitro three-dimensional (3D) platforms to investigate the impact of FNT-P and FNW-P on ECs within a 3D environment. The addition of FNW-P or FNT-P (50 µg/mL) in the hydrogel system led to proliferation rates of ECs up to ~323% and ~280%, respectively, after 7 days of culture. The ECs in FNW-P hydrogel displayed an elongated shape with aligned morphology, while those in FNT-P hydrogel exhibited a rounded and clustered distribution. Vascular-related gene expressions of ECs were significantly upregulated through interactions with these fullerenes. Thus, the combined use of different nanoarchitectured self-assembled fullerenes and self-healing hydrogels may offer environmental cues influencing EC development in a 3D biomimetic microenvironment, holding promise for advancing vascularization strategy in tissue engineering.
Self-assembled fullerenes with large aspect ratios modulate the morphology and gene expression of endothelial cells within a soft biomimetic 3D microenvironment, representing a promising new vascularization strategy in tissue engineering.
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Hepatocellular carcinoma is one of the most common malignant tumors in the world and shows strong metastatic potential. Current medicine for hepatocellular carcinoma therapy is invalid, while Scutellaria baicalensis Georgi exhibits the pharmaceutical potential to treat liver diseases and liver cancer. Herein, we verified the inhibitory properties and the pivotal molecules regimented by Scutellaria baicalensis on advanced hepatocellular carcinoma. At first, the viability of SK-Hep-1 cells was significantly reduced under treatment of Scutellaria baicalensis extract in a dose-dependent manner without affecting the growth of normal hepatocyte. Scutellaria baicalensis extract application could remarkably cause apoptosis of SK-Hep-1 cells through p53/cytochrome C/poly-ADP ribose polymerase cascades and arrest the cell cycle at the G1/S phase by downregulating cyclin-dependent kinases. Meanwhile, administration of Scutellaria baicalensis extract remarkably attenuated the migration capability as well as suppressed matrix metalloproteinase activity of advanced hepatocellular carcinoma cells. The proteome profiles and network analysis particularly implied that exposure to Scutellaria baicalensis extract downregulated the expression of HSP90ß, and the clinical stage of hepatocellular carcinoma is also positively correlated with the HSP90ß level. Combined treatment of Scutellaria baicalensis extract and HSP90ß siRNAs could markedly enhance the ubiquitination activity and the degradation of vimentin to subsequently inhibit the metastatic property of SK-Hep-1 cells. Moreover, application of Scutellaria baicalensis extract and HSP90ß siRNAs depleted phosphorylation of AKT, which stimulated the expression of p53 and consecutively triggered cell apoptosis. These findings suggest that HSP90ß may be a prospective target for the effective therapy of advanced hepatocellular carcinoma via accelerating apoptosis of hepatocellular carcinoma cells and eliciting mesenchymal-epithelial transition with the administration of Scutellaria baicalensis extract.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Extratos Vegetais , Scutellaria baicalensis , Humanos , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53RESUMO
To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aß_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.
Assuntos
Cápsulas , Disfunção Cognitiva , Medicamentos de Ervas Chinesas , Epimedium , Flavonas , Ratos Sprague-Dawley , Acidente Vascular Cerebral , Animais , Ratos , Epimedium/química , Masculino , Flavonas/administração & dosagem , Flavonas/farmacologia , Flavonas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Humanos , Peptídeos beta-Amiloides/metabolismo , NF-kappa B/metabolismo , NF-kappa B/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Cognição/efeitos dos fármacosRESUMO
Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the ß-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease.
Assuntos
Sistema Nervoso Autônomo , Coração , Humanos , Sistema Nervoso Autônomo/fisiologia , Arritmias Cardíacas , Sistema Nervoso Parassimpático , Sistema Nervoso Simpático , Frequência Cardíaca/fisiologia , Nó SinoatrialRESUMO
BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.