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In central nervous system vascular endothelial cells, signaling via the partially redundant ligands WNT7A and WNT7B requires two co-activator proteins, GPR124 and RECK. WNT7A and RECK have been shown previously to play a role in limb development, but the mechanism of RECK action in this context is unknown. The roles of WNT7B and GPR124 in limb development have not been investigated. Using combinations of conventional and/or conditional loss-of-function alleles for mouse Wnt7a, Wnt7b, Gpr124 and Reck, including a Reck allele that codes for a protein that is specifically defective in WNT7A/WNT7B signaling, we show that reductions in ligand and/or co-activator function synergize to cause reduced and dysmorphic limb bone growth. Two additional limb phenotypes - loss of distal Lmx1b expression and ectopic growth of nail-like structures - occur with reduced Wnt7a/Wnt7b gene copy number and, respectively, with Reck mutations and with combined Reck and Gpr124 mutations. A third limb phenotype - bleeding into a digit - occurs with the most severe combinations of Wnt7a/Wnt7b, Reck and Gpr124 mutations. These data imply that the WNT7A/WNT7B-FRIZZLED-LRP5/LRP6-GPR124-RECK signaling system functions as an integral unit in limb development.
Assuntos
Embrião de Mamíferos/metabolismo , Extremidades/embriologia , Proteínas Ligadas por GPI/metabolismo , Receptores Acoplados a Proteínas G , Proteínas Wnt , Animais , Sistema Nervoso Central/metabolismo , Células Endoteliais/metabolismo , Ligantes , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
Acoustic microfluidic devices have advantages for diagnostic applications, therapeutic solutions, and fundamental research due to their contactless operation, simple design, and biocompatibility. However, most acoustofluidic approaches are limited to forming simple and fixed acoustic patterns, or have limited resolution. In this study,a detachable microfluidic device is demonstrated employing miniature acoustic holograms to create reconfigurable, flexible, and high-resolution acoustic fields in microfluidic channels, where the introduction of a solid coupling layer makes these holograms easy to fabricate and integrate. The application of this method to generate flexible acoustic fields, including shapes, characters, and arbitrarily rotated patterns, within microfluidic channels, is demonstrated.
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Numerous intrinsic factors regulate mesenchymal progenitor commitment to a specific cell fate, such as osteogenic or adipogenic lineages. Identification and modulation of novel intrinsic regulatory factors represent an opportunity to harness the regenerative potential of mesenchymal progenitors. In the present study, the transcription factor (TF) ZIC1 was identified to be differentially expressed among adipose compared with skeletal-derived mesenchymal progenitor cells. We observed that ZIC1 overexpression in human mesenchymal progenitors promotes osteogenesis and prevents adipogenesis. ZIC1 knockdown demonstrated the converse effects on cell differentiation. ZIC1 misexpression was associated with altered Hedgehog signaling, and the Hedgehog antagonist cyclopamine reversed the osteo/adipogenic differentiation alterations associated with ZIC1 overexpression. Finally, human mesenchymal progenitor cells with or without ZIC1 overexpression were implanted in an ossicle assay in NOD-SCID gamma mice. ZIC1 overexpression led to significantly increased ossicle formation in comparison to the control, as assessed by radiographic and histologic measures. Together, these data suggest that ZIC1 represents a TF at the center of osteo/adipogenic cell fate determinations-findings that have relevance in the fields of stem cell biology and therapeutic regenerative medicine.
Assuntos
Adipogenia , Células-Tronco Mesenquimais , Animais , Camundongos , Humanos , Adipogenia/genética , Proteínas Hedgehog , Osteogênese/fisiologia , Camundongos Endogâmicos NOD , Camundongos SCID , Diferenciação Celular , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Resistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown. METHODS: PEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interference in vitro and in vivo. Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches. RESULTS: The lung cancer brain metastatic subpopulation cells (PC9-BrM3) exhibited significant resistance to PEM and silencing AKR1B10 in PC9-BrM3 increased the PEM sensitivity in vitro and in vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle. CONCLUSIONS: Our finding demonstrates that AKR1B10/glycolysis/H4K12la/CCNB1 promotes acquired PEM chemoresistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Pemetrexede , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Aldo-Ceto Redutases , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/farmacologia , Pemetrexede/uso terapêuticoRESUMO
BACKGROUND: The lack of non-invasive methods for detection of early micro-metastasis is a major cause of the poor prognosis of non-small cell lung cancer (NSCLC) brain metastasis (BM) patients. Herein, we aimed to identify circulating biomarkers based on proteomics for the early diagnosis and monitoring of patients with NSCLC BM. METHODS: Upregulated proteins were detected by secretory proteomics in the animal-derived high brain metastatic lung cancer cell line. A well-designed study composed of three independent cohorts was then performed to verify these blood-based protein biomarkers: the serum discovery and verification cohorts (n = 80; n = 459), and the tissue verification cohort (n = 76). Logistic regression was used to develop a diagnostic biomarker panel. Model validation cohort (n = 160) was used to verify the stability of the constructed predictive model. Changes in serum Cathepsin F (CTSF) levels of patients were tracked to monitor the treatment response. Progression-free survival (PFS) and overall survival (OS) were analysed to assess their prognostic relevance. RESULTS: CTSF and Fibulin-1 (FBLN1) levels were specifically upregulated in sera and tissues of patients with NSCLC BM compared with NSCLC without BM and primary brain tumour. The combined diagnostic performance of CTSF and FBLN1 was superior to their individual ones. CTSF serum changes were found to reflect the therapeutic response of patients with NSCLC BM and the trends of progression were detected earlier than the magnetic resonance imaging changes. Elevated expression of CTSF in NSCLC BM tissues was associated with poor PFS, and was found to be an independent prognostic factor. CONCLUSIONS: We report a novel blood-based biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with NSCLC BM.
Assuntos
Neoplasias Encefálicas , Proteínas de Ligação ao Cálcio , Carcinoma Pulmonar de Células não Pequenas , Catepsina F , Neoplasias Pulmonares , Animais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Catepsina F/sangue , Catepsina F/metabolismo , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Prognóstico , Regulação para CimaRESUMO
Coal fly ash (CFA) is an ideal source for the preparation of heterogeneous catalysts due to its abundant silicon and aluminum oxides, but its activity needs to be improved. In this study, a green and moderate approach for CFA activation was proposed, and a series of CFA-based catalysts were prepared for NO selective catalytic reduction (SCR). The results indicated that CFA could be well activated via mechanochemical activation with 3 h of milling duration in 1 mol/L of acetic acid, and 90% of NO removal was achieved over the CFA-based catalyst in 250 to 375 °C. Two activating mechanisms, i.e., the enhanced CFA fragmentation and the motivated Al dissolution, were revealed during the mechanochemical activation. The former facilitated the formation of mesopores and the exposure of Fe components in CFA fragments, which enhanced the capacity of oxygen storage over the as-activated catalyst. The latter motivated the formation of Si-OH groups, which promoted the migration of electrons and the dispersion of V species, thereby increasing the capacity of NH3 adsorption over the as-obtained catalyst. Therefore, the performance of NO reduction was improved. The proposed activating approach could be a promising integration for CFA disposal and NO removal from inside coal-fired power plants.
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Cinza de Carvão , Carvão Mineral , Adsorção , Catálise , Centrais ElétricasRESUMO
OBJECTIVE: The network pharmacology approach combined the technologies of molecular docking and in vitro bacteriostatic validation to explore the active compounds, core targets, and mechanism of Mung Bean against bacterial infection. METHODS: A Mung Bean target and anti-bacterial infection-related gene set was established using TCMSP and GeneCards databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network were performed using DAVID and STRING database. The combination of core targets and active compounds was predicted by molecular docking. The bacteriostatic experiment in vitro was performed to verify the antibacterial activity of the active compounds. RESULT: 32 potential targets and 5 active compounds of Mung Bean against bacterial infection were obtained by bioinformatics analysis. SRC, EGFR, and MAPK8 might be the candidate targets of Mung Bean. There were 137 GO items (p < 0.05) and 60 signaling pathways (p < 0.05) in GO and KEGG enrichment analysis. The PI3K-AKT pathway, TNF signaling pathway, MAPK signaling pathway might play a significant role in Mung Bean against bacterial infection. Molecular docking results showed that sitosterol and vitamin-e had a high binding affinity with the core targets, which might be the key compounds of Mung bean. In vitro bacteriostatic experimental verified that vitamin-e had a significant bacteriostatic effect. CONCLUSION: Sitosterol and vitamin-E in Mung bean might act on MAPK1, regulate inflammation and immune response to play a role in anti-bacterial infection.
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Medicamentos de Ervas Chinesas , Vigna , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Sitosteroides , VitaminasRESUMO
The present study aimed at evaluating the mechanism by which functionality of hepatic stellate cells (HSCs) is modulated by bone marrow stromal cells (BMSCs). Induction of apoptosis in HSCs was found to be caused by directly co-culturing HSCs with BMSCs, where the expression of α-smooth muscle actin (α-SMA) increased significantly in HSCs, along with an increase in their proliferation rate. Additionally, expression of Hes1 and Notch1 in HSCs co-cultured with BMSCs increased significantly at both protein and mRNA levels. Blocking of the notch signaling pathway (NSP) either by Notch1 siRNA or by DAPT treatment increased the proliferation rate while decreasing apoptosis and led to activation of the NF-κB signaling pathway in HSCs co-cultured with BMSCs. These effects were found to be reversed in HSCs overexpressing IκB S32/S36 mutants. The Notch signaling-mediated cell-cell contact was partially involved in the significant inhibition of proliferation of HSCs by BMSCs. Additionally, the NF-κB pathway was found to be responsible for NSP-mediated inhibition of growth of HSCs in the co-culture system. Thus, BMSCs might have a potential therapeutic significance in treating hepatic fibrosis.
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Apoptose , Medula Óssea/metabolismo , Células Estreladas do Fígado/metabolismo , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Receptores Notch/metabolismo , Células Cultivadas , Técnicas de Cocultura , Humanos , Transdução de SinaisRESUMO
Circulating tumor cells (CTCs) represent invasive tumor cell populations and provide a noninvasive solution to the clinical management and research of tumors. Characterization of CTCs at single-cell resolution enables the comprehensive understanding of tumor heterogeneity and may benefit the diagnosis and treatment of cancer patients. However, most efforts have been made on enumeration and detection of CTCs, while little focus has been directed to single-cell study. Herein, an integrated microfluidic platform for single-cell isolation and analysis was established. After validating this platform on lung cancer cell lines, we detected and isolated single CTCs from the peripheral blood samples of 20 cancer patients before and after one treatment cycle. Furthermore, we performed single-cell whole-exome DNA sequencing on a single CTC from the peripheral blood sample of a representative early stage lung cancer patient. Among the blood samples of 20 patients, 15 of them were positive for CTC detection (75.0% detectable rate). Single-cell analysis revealed detailed genetic variations of the CTC, while six new gene mutations were detected in both single CTC and surgical specimen. This study provides a useful tool for the isolation and analysis of single CTCs from peripheral blood samples, which not only facilitates the early diagnosis of cancers but also helps to unravel the genetic information of tumor at a single-cell level. © 2019 International Society for Advancement of Cytometry.
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Neoplasias Pulmonares/patologia , Microfluídica , Células Neoplásicas Circulantes/patologia , Análise de Célula Única , Idoso , Linhagem Celular Tumoral , Separação Celular/métodos , Feminino , Humanos , Masculino , Técnicas Analíticas Microfluídicas , Microfluídica/métodos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Célula Única/métodosRESUMO
Accumulating evidence has demonstrated that serum uric acid (UA), a natural powerful antioxidant, plays a beneficial role in bone health in the general population. However, few reports are available on the association between serum UA and bone in patients with type 2 diabetes mellitus (T2DM). We therefore investigated whether the benefit of serum UA for bone health was still present in those patients. 626 males and 609 postmenopausal females with T2DM were enrolled in this cross-sectional study. Serum UA concentrations and bone mineral density (BMD) measured at lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry were obtained from all subjects. Meanwhile, data on osteoporosis prevalence, glucose metabolism, bone turnover markers and other serum biochemical indexes were collected. After adjustment for potential confounders, the results suggested that serum UA was positively associated with BMD in patients with normal weight, but this positive association varied by gender and skeletal sites in overweight T2DM patients [body mass index (BMI) ≥ 25 kg/m2]. Moreover, significantly lower odds ratios (ORs) for osteoporosis were found in postmenopausal patients with the highest UA tertile and male patients with medium UA tertile [adjusted OR 0.315, 95% confidence interval (CI) 0.170-0.581 for postmenopausal patients; adjusted OR 0.464, 95% CI 0.225-0.955 for male patients]. The positive association between serum UA and BMD found in Chinese T2DM patients may imply that relatively high UA is a protective factor for bone in these patients. Large intervention studies are needed to further confirm the outcomes and provide possible explanations.
Assuntos
Povo Asiático , Índice de Massa Corporal , Densidade Óssea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Ácido Úrico/sangue , Idoso , Biomarcadores/metabolismo , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/epidemiologia , Remodelação Óssea , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Razão de Chances , Osteoporose/sangue , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , PrevalênciaRESUMO
Sleep apnea is a serious sleep disorder, and the most common type is obstructive sleep apnea (OSA). Untreated OSA will cause lots of potential health problems. Oral appliance therapy is an effective and popular approach for OSA treatment, but making a perfect fit for each patient is time-consuming and decreases its efficiency considerably. This paper proposes a System-on-a-Chip (SoC) enabled sleep monitoring system in a smart oral appliance, which is capable of intelligently collecting the physiological data about tongue movement through the whole therapy. A tunneling sensor array with an ultra-high sensitivity is incorporated to accurately detect the subtle pressure from the tongue. When the device is placed on the wireless platform, the temporary stored data will be retrieved and wirelessly transmitted to personal computers and cloud storages. The battery will be recharged by harvesting external RF power from the platform. A compact prototype module, whose size is 4.5 × 2.5 × 0.9 cm³, is implemented and embedded inside the oral appliance to demonstrate the tongue movement detection in continuous time frames. The functions of this design are verified by the presented measurement results. This design aims to increase efficiency and make it a total solution for OSA treatment.
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Técnicas Biossensoriais/instrumentação , Polissonografia/instrumentação , Apneia Obstrutiva do Sono/terapia , Tecnologia sem Fio , Humanos , Apneia Obstrutiva do Sono/diagnósticoRESUMO
The efficacy of combined vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibition in patients with advanced non-small-cell lung cancer (NSCLC) was well studied. However, few studies focused on the risk and adverse events (AEs) of combined targeted therapy. The aim of this meta-analysis was to evaluate the safety profile of combined targeted therapy against EFGR and VEGF in patients with advanced NSCLC. A comprehensive literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts and ESMO Abstracts was conducted. Eligible studies were randomized clinical trials (RCTs) that compared safety profile of combined therapy inhibiting EFGR and VEGF pathways with control groups (placebo, single EGFR or VEGF inhibition therapy, chemotherapy or a combination of them) in patients with advanced NSCLC. The endpoints included treatment discontinuation, treatment-related deaths and AEs. The search identified 15 RCTs involving 6,919 patients. The outcomes showed that three of four pairwise comparisons detected more discontinuation due to AEs in combined targeted therapy, with odds ratio (OR) compared with the control groups ranged from 1.97 to 2.29. Treatment with combined inhibition therapy was associated with several all-grade and grade 3 or 4 AEs (e.g. rash, diarrhea and hypertension). Also, there was a significantly higher incidence of treatment-related deaths in combined inhibition using vandetanib versus single EGFR inhibition therapy (OR = 1.97, 95% CI 1.19-3.28). In conclusion, combined inhibition therapy against EGFR and VEGF in patients with advanced NSCLC was associated with increased toxicity. Increased AEs hinder patient compliance and reduce their quality of life, leading to dose reduction or discontinuation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Diarreia/induzido quimicamente , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Humanos , Neoplasias Pulmonares/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Microparticles are small membrane fragments shed primarily from blood and endothelial cells during either activation or apoptosis. There is mounting evidence suggesting that microparticles perform a large array of biological functions and contribute to various diseases. Of these disease processes, a significant link has been established between microparticles and venous thromboembolism. Advances in research on the role of microparticles in thrombosis have yielded crucial insights into possible mechanisms, diagnoses and therapeutic targets of venous thromboembolism. In this review, we discuss the definition and properties of microparticles and venous thromboembolism, provide a synopsis of the evidence detailing the contributions of microparticles to venous thromboembolism, and propose potential mechanisms, by which venous thromboembolism occurs. Moreover, we illustrate a possible role of microparticles in cancer-related venous thromboembolism.
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Micropartículas Derivadas de Células/patologia , Tromboembolia Venosa/patologia , Apoptose/fisiologia , Células Endoteliais/patologia , Humanos , Neoplasias/patologiaRESUMO
BACKGROUND: Atherosclerosis is a chronic inflammatory process, in which oxidative stress is the key event. Gamma-glutamyl transferase (GGT) is a cellular production of oxidants. We aimed to elucidate the relationship of serum GGT levels and coronary artery disease (CAD) in a Chinese population. MATERIAL AND METHODS: A total of 513 adult subjects who had undergone coronary angiography were enrolled in the study. Clinical characteristics, coronary angiography, and serum samples were collected from all the patients and analyzed for the serum GGT, blood lipids, and cardiovascular risk factors. RESULTS: Subjects with CAD had significantly increased activity of serum GGT (p=0.003). Serum GGT levels exhibited positive correlations with alcohol intake (ß=0.177, p<0.001), coronary complexity (ß=0.068, p<0.001), and triacylglycerol (ß=0.058, p<0.001). High-density lipoprotein cholesterol levels (ß=0.157, p=0.008) and age (ß=0.004, p=0.002) were negatively correlated with serum GGT in the CAD group. The coronary complexity presented a negative correlation with Ig-apolipoprotein AI (ß=-2.517, p=0.001) and positive correlations with smoking (ß=0.640, p<0.001), Ig-GGT (ß=0.613, p=0.004), Ig high sensitivity-C reactive protein (ß=0.320, p<0.001), and hypertension (ß=0.286, p<0.026). CONCLUSIONS: The study showed a positive correlation between serum GGT and CAD in a Chinese population. Serum GGT levels may be a potential biomarker for CAD.
Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/enzimologia , gama-Glutamiltransferase/sangue , Adulto , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de RiscoRESUMO
The intestinal tract of humans harbors a dynamic and complex bacterial community known as the gut microbiota, which plays a crucial role in regulating functions such as metabolism and immunity in the human body. Numerous studies conducted in recent decades have also highlighted the significant potential of the gut microbiota in promoting human health. It is widely recognized that training and nutrition strategies are pivotal factors that allow athletes to achieve optimal performance. Consequently, there has been an increasing focus on whether training and dietary patterns influence sports performance through their impact on the gut microbiota. In this review, we aim to present the concept and primary functions of the gut microbiota, explore the relationship between exercise and the gut microbiota, and specifically examine the popular dietary patterns associated with athletes' sports performance while considering their interaction with the gut microbiota. Finally, we discuss the potential mechanisms by which dietary patterns affect sports performance from a nutritional perspective, aiming to elucidate the intricate interplay among dietary patterns, the gut microbiota, and sports performance. We have found that the precise application of specific dietary patterns (ketogenic diet, plant-based diet, high-protein diet, Mediterranean diet, and high intake of carbohydrate) can improve vascular function and reduce the risk of illness in health promotion, etc., as well as promoting recovery and controlling weight with regard to improving sports performance, etc. In conclusion, although it can be inferred that certain aspects of an athlete's ability may benefit from specific dietary patterns mediated by the gut microbiota to some extent, further high-quality clinical studies are warranted to substantiate these claims and elucidate the underlying mechanisms.
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Atletas , Desempenho Atlético , Dieta , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Desempenho Atlético/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Padrões DietéticosRESUMO
The recycling of end-of-life wind turbine blades has become a global environmental challenge driven by the rapid growth of wind power. Pyrolysis is a promising method for recovering glass fibers from these discarded blades, but traditional pyrolysis is often operated at high temperatures, which degrades the mechanical properties of recovered fibers. To address this issue, a swelling-assisted pyrolysis method was proposed to recover high-quality glass fibers from end-of-life wind turbine blades at low temperatures. The results confirmed that the decomposition of the resin matrix within the blade was significantly promoted at low temperatures in the swelling-assisted pyrolysis process, achieving a resin decomposition ratio of 76.8 % at 350 °C. This improvement was attributed to enhanced heat transfer and co-pyrolysis with acetic acid. Swelling could physically disrupt the cross-linked structure of the blade, creating a more porous and layered structure, thereby enhancing heat transfer during the pyrolysis process. Simultaneously, the co-pyrolysis with acetic acid could generate hydrogen radicals, which promoted the cracking of macromolecular oligomers into lighter products or gaseous alkanes. Consequently, the formation of pyrolysis char within the solid pyrolysis product was reduced, shortening the oxidation duration to 30 min. In comparison to traditional pyrolysis, the swelling-assisted pyrolysis process effectively suppressed the diffusion of surface defects over the recovered fibers, leading to promising improvements in their flexibility, elasticity, and mechanical properties, with tensile strength notably increased by 27.5 %. These findings provided valuable insights into recovering high-quality glass fibers from end-of-life wind turbine blades.
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Vidro , Pirólise , Reciclagem , Vidro/química , Reciclagem/métodos , Vento , Temperatura Alta , Centrais ElétricasRESUMO
Carbon fiber-reinforced polymer composites (CFRPs) have gained widespread usage due to their promising physiochemical properties, while this causes large amounts of waste CFRPs worldwide. In this study, carbon fibers were successfully recovered from waste CFRPs through the pyrolysis-oxidation method, and the recovered fibers were reused in remanufacturing the secondary generation CFRPs. Moreover, the individual and interactive effects of pyrolysis-oxidation recovering parameters on the mechanical strength of the resulting remanufactured CFRPs (reCFRPs) were investigated. The recovered carbon fibers displayed surface chemical structures similar to virgin fibers but with high contents of oxygen-containing bonds. The tensile strength retention (TSR) of the reCFRPs was primarily influenced by oxidation temperature. Notably, a higher oxidation temperature, especially exceeding 560 °C, amplified the impact of oxidation duration on the TSR value. Similarly, concerning interlaminar shear strength retention (ISSR), the oxidation stage had a more substantial effect compared to the pyrolysis stage. As the oxidation temperature increased from 500 °C to 600 °C, the ISSR value initially increased and then decreased, irrespective of variations in pyrolysis parameters. Additionally, through integrating the response surface methodology (RSM) analysis and multi-island genetic algorithm (MIGA) global optimization, three recovery strategies, along with the corresponding processing parameters, were proposed to meet diverse requirements. The conclusions could provide valuable insights for optimizing the recovery and reuse of carbon fibers from waste CFRPs.
Assuntos
Fibra de Carbono , Oxirredução , Pirólise , Reciclagem , Fibra de Carbono/química , Reciclagem/métodos , Resistência à Tração , Polímeros/química , Carbono/químicaRESUMO
Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in three stages of injury repair (inflammatory, reparative, and remodeling) in two commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.
Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing.
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Patients who have non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations are more prone to brain metastasis (BM) and poor prognosis. Previous studies showed that the tumor microenvironment of BM in these patients is immunosuppressed, as indicated by reduced T-cell abundance and activity, although the mechanism of this immunosuppression requires further study. This study shows that reactive astrocytes play a critical role in promoting the immune escape of BM from EGFR-mutated NSCLC by increasing the apoptosis of CD8+ T lymphocytes. The increased secretion of interleukin 11(IL11) by astrocytes promotes the expression of PDL1 in BM, and this is responsible for the increased apoptosis of T lymphocytes. IL11 functions as a ligand of EGFR, and this binding activates EGFR and downstream signaling to increase the expression of PDL1, culminating in the immune escape of tumor cells. IL11 also promotes immune escape by binding to its intrinsic receptor (IL11Rα/glycoprotein 130 [gp130]). Additional in vivo studies show that the targeted inhibition of gp130 and EGFR suppresses the growth of BM and prolongs the survival time of mice. These results suggest a novel therapeutic strategy for treatment of NSCLC patients with EGFR mutations.
Assuntos
Astrócitos , Antígeno B7-H1 , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Interleucina-11 , Neoplasias Pulmonares , Regulação para Cima , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Receptores ErbB/metabolismo , Receptores ErbB/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Humanos , Astrócitos/metabolismo , Interleucina-11/genética , Interleucina-11/metabolismo , Regulação para Cima/genética , Evasão Tumoral/genética , Modelos Animais de Doenças , Mutação/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Linhagem Celular TumoralRESUMO
BACKGROUND: Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. METHODS: The expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies. RESULTS: MSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice. CONCLUSIONS: Our results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.