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Decabrominated diphenyl ether (BDE-209) is a typical persistent organic pollutant that can cross the placental barrier, increasing the exposure risk for offspring. Norepinephrine (NE) from nerve terminals and acetylcholine (Ach) can bind to specific receptors on immune cells, inhibit the immune function of the body then cause immunotoxicity. However, whether maternal exposure to BDE-209 could lead to immunotoxicity in the offspring by acting on the sympathetic and parasympathetic nervous systems remains unclear. In view of this, the pregnancy and lactation rat BDE-209 exposure model was established and the results demonstrated that pregnancy and lactation BDE-209 exposure could induce immunotoxicity to female offspring via affecting immunopathology (hematological and biochemical parameters, organ indices, and spleen histopathological), decreasing humoral immunity (serum hemolysin, immunoglobulins, and cytokine productions), damaging cellular immunity (splenic lymphocytes and spleen cytokine productions), and restraining nonspecific immunity. Moreover, a dramatically significant correlation was observed between spleen nerve indices and immunity indices. Additionally, the mechanism revealed that maternal BDE-209 exposure caused offspring immunotoxicity through (1) activating MHC/PKCθ/NF-κB pathway; (2) promoting sympathetic nervous pathway, by upregulating the expression of ß2AR protein, which in turn elevating cAMP, following activate PKA and phosphorylate CREB, ultimately leading to immunotoxicity;(3) activating parasympathetic nerve pathway by reducing the binding with Ach and α7nAchR, upregulating the expression of JAK2 and phosphorylating STAT3, induced immunotoxicity of female offspring.
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Éteres Difenilos Halogenados , Exposición Materna , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Embarazo , Éteres Difenilos Halogenados/toxicidad , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Bazo/efectos de los fármacos , Bazo/inmunología , Sistema Nervioso Autónomo/efectos de los fármacos , Ratas Sprague-Dawley , Contaminantes Ambientales/toxicidad , Masculino , Citocinas/metabolismoRESUMEN
An efficient cathode for a Fenton-like reaction based on hydrogen peroxide (H2O2) has significant implications for the potential application of the advanced oxidation process. However, the low H2O2 selectivity and efficient activation remain challenging in wastewater treatment. In the present study, a single Fe atom doped, nitrogen-coordinated molybdenum disulfide (Fe1/N/MoS2) cathode that exhibited asymmetric wettability and self-absorption molecular oxygen was successfully prepared for pollutant degradation. The X-ray absorption near-edge structure and extended X-ray absorption fine structure of Fe1N3 in the Fe1/N/MoS2 catalyst were determined. The electronic structure demonstrated favorable H2O2 selectivity (75%) in a neutral solution and the cumulative hydroxyl radical concentration was 14 times higher than the pure carbon felt. After 10 consecutive reaction experiments, the removal ratio of paracetamol still reached 97%, and the catalytic performance did not decrease significantly. This work deeply understands the catalytic mechanism of Fenton-like reaction between single Fe atom and MoS2 double reaction sites, and proves that the regulation of the electronic structure of Fe single atom is an effective strategy to improve the activity of Fenton-like reaction.
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In this work, WO3 nanorod-based aggregates and WO3 nano-shuttles were constructed by a facile hydrothermal route. The structure, morphology, element composition and valence state of the formed WO3 samples were characterized using different testing instruments. As the active anode for lithium-ion batteries, the WO3 nano-shuttle electrode can deliver a reversible specific capacity of 614.7 mA h g-1 after 300 cycles at a current density of 500 mA g-1. The excellent electrochemical properties indicate that WO3 nano-shuttles are a prospective anode candidate for high performance lithium-ion batteries.
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Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.
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Enzima Convertidora de Angiotensina 2 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Neoplasias Hepáticas/metabolismo , Especies Reactivas de Oxígeno , AnimalesRESUMEN
PURPOSE: Transglutaminases (TGs) are multifunctional enzymes exhibiting transglutaminase crosslinking, as well as atypical GTPase/ATPase and kinase activities. Here, we used an integrated comprehensive analysis to assess the genomic, transcriptomic and immunological landscapes of TGs across cancers. METHODS: Gene expression and immune cell infiltration patterns across cancers were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Enrichment Analysis (GSEA) datasets. Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assays, and orthotopic xenograft models were used to validate our database-derived results. RESULTS: We found that the overall expression of TGs (designated as the TG score) is significantly upregulated in multiple cancers and related to a worse patient survival. The expression of TG family members can be regulated through multiple mechanisms at the genetic, epigenetic and transcriptional levels. The expression of transcription factors crucial for epithelial-to-mesenchymal transition (EMT) is commonly correlated with the TG score in many cancer types. Importantly, TGM2 expression displays a close connection with chemoresistance to a wide range of chemotherapeutic drugs. We found that TGM2 expression, F13A1 expression and the overall TG score were positively correlated with the infiltration of immune cells in all cancer types tested. Functional and clinical verification revealed that a higher TGM2 expression is linked with a worse patient survival, an increased IC50 value of gemcitabine, and a higher abundance of tumor-infiltrating macrophages in pancreatic cancer. Mechanistically, we found that increased C-C motif chemokine ligand 2 (CCL2) release mediated by TGM2 contributes to macrophage infiltration into the tumor microenvironment. CONCLUSIONS: Our results reveal the relevance and molecular networks of TG genes in human cancers and highlight the importance of TGM2 in pancreatic cancer, which may provide promising directions for immunotherapy and for addressing chemoresistance.
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Neoplasias Pancreáticas , Transglutaminasas , Humanos , Transglutaminasas/genética , Transglutaminasas/metabolismo , Proteína Glutamina Gamma Glutamiltransferasa 2 , Resistencia a Antineoplásicos/genética , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Biomarcadores , Macrófagos/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Microambiente Tumoral , Neoplasias PancreáticasRESUMEN
Solar steam generation (SSG) is considered an effective solution to the global shortage of freshwater resources. To solve the practical application challenges of SSG in remote outdoor environments where electricity is scarce, it is of great importance to developing new solar evaporators. In this study, a three-dimensional (3D) biochar solar evaporator based on carbonized grooved straw was prepared from agricultural waste corn straw, which had high solar energy conversion efficiency and excellent salt resistance. The existence of grooves increases the surface area to absorb more sunlight and makes the light multilevel reflection improve the evaporation rate. The excellent light absorption, super hydrophilic, and heat shielding properties of 3D carbonized grooved straw resulted in a good evaporation rate (1.57 kgâ m-2·h-1) and energy efficiency (85.9%) under 1 sun irradiation. The 3D grooved biochar solar distiller also demonstrated efficient formation evaporation performance and excellent salt resistance in practical applications in seawater desalination and surface water purification. The 3D grooved biochar solar distiller prepared from agricultural waste has the advantages of being economical and environmentally friendly, with good application prospects.
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Energía Solar , Vapor , Luz Solar , Cloruro de SodioRESUMEN
A synthetic strategy for fabricating colloidal particles with spatially segregated amine-functionalized lobes enables regioselective coating with gold to afford metallodielectric particles with a variety of shapes and lobe sizes. This approach can produce either dissymmetric dumbbell-shaped two-lobed Au-TPM particles (Au-T) or dissymmetric or symmetric three-lobed particles with gold coating on one (Au-T-T and T-Au-T) or two lobes (Au-T-Au). Dielectrophoretic (DEP) forces exerted by an AC field confined between two opposing electrodes generate aggregates ranging from 1D chains to 2D close-packed lattices, depending on the particle shape and lobe arrangement. The aggregate structures reflect the lowest energy configurations resulting from the induced dipole moments created in particle lobes within the confined electric field.
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m6A is a widespread RNA modification. However, the mechanism through which m6A regulated the progress of oesophageal squamous cell carcinoma (ESCC) remains undetermined. The levels and prognosis of WTAP were analysed using an ESCC tissue microarray (87 ESCC and 44 paracancerous tissues). TCGA and Oncolnc databases validate WTAP expression and prognosis. CCK8, colony formation (CF), wound healing, transwell cell invasion (CI), and migration (CM) assays were employed for the detection of the biological impacts of WTAP. Expression of tumour stemness-related genes was assessed via qRT-PCR and western blotting. The m6A RNA methylation (m6AMe) quantitative kit was employed for cellular methylation level detection. Arraystar m6A-mRNA and lncRNA epitranscriptomic microarray analyses were used to screen low methylation, high expression, and prognosis-related candidate gene CPSF4. KEGG enrichment analysis was used to screen the downstream signalling pathways of CPSF4. WTAP, a methyltransferase "writer", was markedly enhanced in ESCC and was strongly correlated with poor patient outcome. WTAP knockdown inhibited the cell proliferation (CP), CI, CM, and stemness of ESCC cells in vitro and reduced the overall m6A modification (m6AMo) percentage of ESCC cells. CPSF4 is a target of WTAP-based m6AMo. WTAP-based m6AMo of CPSF4 transcript reduced the stability of CPSF4 by relying on YTHDF2. We identified the significant role of WTAP-catalysed m6AMo in ESCC tumourigenesis, wherein it facilitates ESCC tumour growth and metastasis through decreasing CPSF4 expression in an m6A-dependent manner.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , ARN Largo no Codificante , Carcinogénesis , Proteínas de Ciclo Celular , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Factores de Empalme de ARN , Factores de TranscripciónRESUMEN
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance (IR) and has attracted worldwide attention due to its high prevalence. As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) has been detected in food and human samples, and the concentration trends increase year by year. In addition, it has been proved to have the potential to increase the risk of IR, but it is rarely reported whether it could aggravate IR in T2DM. Therefore, in this study, the IR-BRL (buffalo rat liver cells with IR) model was applied to study the metabolism toxicity and susceptibility of BDE-209. Results showed that BDE-209 could inhibit glucose absorption and increase the levels of serum total cholesterol (TC) and triglyceride (TG), ultimately leading to the disorder of glucolipid metabolism in IR-BRL cells. Besides, it also could cause cell damage by increasing the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in cells. Moreover, its potential mechanisms were to: (1) affect the transport of glucose, synthesis of glycogen and fatty acid via IRS-1/GLUT4 and IRS-1/PI3K/AKT/GSK-3ß pathways; (2) impact the proliferation and differentiation by regulating the expression of Mek1/2, Erk1/2, and mTOR proteins and genes. Furthermore, susceptibility analysis showed that there was a significant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.
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Diabetes Mellitus Tipo 2 , Éteres Difenilos Halogenados , Resistencia a la Insulina , Glucosa , Glucógeno Sintasa Quinasa 3 beta , Fosfatidilinositol 3-Quinasas , Animales , Línea Celular , Éteres Difenilos Halogenados/toxicidadRESUMEN
BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Neoplasias Encefálicas , Neoplasias de la Mama , Acrilamidas , Aminoquinolinas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Capecitabina , Femenino , Humanos , Masculino , Estudios Prospectivos , Receptor ErbB-2/metabolismoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease globally. Elderly individuals are at a higher risk of developing NAFLD with severe clinical outcomes. Although NAFLD is closely related to liver aging, the role of hepatocyte senescence in the progression of NAFLD, especially in the development of fibrosis, is still unclear. The early stage of NAFLD is mainly characterized by lipid accumulation in hepatocytes, which could lead to severe oxidative stress, causing cellular senescence. In the present study, hepatocytes cultured in the presence of free fatty acids to induce lipid deposition were used as a hepatocyte senescence model in vitro. Senescent hepatocytes significantly increased the activation of co-cultured primary hepatic stellate cells (HSCs) and the expression of pro-fibrosis molecules. Moreover, the antioxidant regulator nuclear factor erythroid 2-related factor 2 (Nrf2) that was upregulated in senescent hepatocytes was found to be related to the activation of co-cultured HSCs. The Nrf2 agonist sulforaphane, which upregulated the transcriptional activity of the Nrf2-antioxidant response element (ARE) pathway, remarkably inhibited hepatocyte senescence and its activation effect on HSCs. However, the liver tissue obtained from non-alcoholic steatohepatitis (NASH) mice with Nrf2 knockdown showed decreased antioxidation and significant liver senescence and fibrosis. In conclusion, this study confirmed that lipid accumulation induces hepatocyte senescence, which leads to HSC activation and development of hepatic fibrosis. Increasing the activity of the Nrf2-ARE antioxidant pathway in senescent hepatocytes elicited the opposite effect, suggesting that targeting Nrf2 may prevent or delay the progression of aging-related liver fibrosis in NASH.
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Elementos de Respuesta Antioxidante/fisiología , Hepatocitos/citología , Metabolismo de los Lípidos/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Hígado/metabolismo , Cirrosis Hepática/patología , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacosRESUMEN
BACKGROUND: Reprogrammed glucose metabolism, also known as the Warburg effect, which is essential for tumor progression, is regarded as a hallmark of cancer. MAP17, a small 17-kDa non-glycosylated membrane protein, is frequently dysregulated in human cancers. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. METHODS: Immunohistochemistry was used to analyze the expression pattern of MAP17 in HCC. Loss-of-function and gain-of-function studies were performed to investigate the oncogenic roles of MAP17 in vitro and in vivo. RNA sequencing, co-immunoprecipitation, immunofluorescence and western blotting were used to study the molecular mechanism of MAP17 affecting the tumor growth and glycolytic phenotype of HCC. RESULTS: An integrative analysis showed that MAP17, a small 17-kDa non-glycosylated membrane protein, is significantly related to the glycolytic phenotype of hepatocellular carcinoma (HCC). Firstly, we found that MAP17 expression is hypoxia-dependent and predicts a poor prognosis in HCC. Genetic silencing of MAP17 reduced the rate of glucose uptake, lactate release, extracellular acidification rate, and expression of glycolytic genes. Ectopic expression of wild type MAP17 but not its PDZ binding domain mutant MAP17-PDZm increased tumor glycolysis. Further research showed that MAP17 knockdown markedly retarded in vivo tumor growth in HCC. Importantly, attenuation of tumor glycolysis by galactose largely hijacked the growth-promoting role of MAP17 in HCC cells. RNA sequencing analysis revealed that MAP17 knockdown leads to transcriptional changes in the ROS metabolic process, cell surface receptor signaling, cell communication, mitotic cell cycle progression, and regulation of cell differentiation. Mechanistically, MAP17 exerted an increased tumoral phenotype associated with an increase in reactive oxygen species (ROS), which activates downstream effectors AKT and HIF1α to enhance the Warburg effect. In HCC clinical samples, there is a close correlation between MAP17 expression and HIF1α or phosphorated level of AKT. CONCLUSIONS: Our results show that MAP17 is a novel glycolytic regulator, and targeting MAP17/ROS pathway may be an alternative approach for the prevention and treatment of HCC.
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Carcinoma Hepatocelular/genética , Inmunohistoquímica/métodos , Neoplasias Hepáticas/genética , Proteínas de la Membrana/metabolismo , Carcinoma Hepatocelular/patología , Hipoxia de la Célula , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , Transfección , Efecto Warburg en OncologíaRESUMEN
BACKGROUND: The mitochondrial (mt) genomes of Sarcoptiformes mites typically contain 37 genes. Although the loss of genes is rare in Sarcoptiformes mite mitogenomes, two of the six previously reported oribatid mites (Acariforms: Sarcoptiformes) are reported to have lost parts of their tRNA genes. To confirm whether the tRNA genes were indeed lost and whether the loss is universal, we re-annotated the available oribatid mite sequences and sequenced the mitogenome of Oribatula sakamorii. METHODS: The mitogenome of O. sakamorii was sequenced using an Illumina HiSeq sequencer. The mt tRNA gene was annotated using multi-software combined with a manual annotation approach. Phylogenetic analyses were performed using the maximum likelihood and Bayesian inference methods with concatenated nucleotide and amino acid sequences. RESULTS: The mitogenomes of O. sakamorii contained 37 genes, including 22 tRNA genes. We identified all mt tRNA genes that were reported as "lost" in Steganacarus magnus and Paraleius leontonychus and revealed certain atypical tRNA annotation errors in oribatid mite sequences. Oribatid mite mitogenomes are characterized by low rates of genetic rearrangement, with six or seven gene blocks conserved between the mitogenome of all species and that of ancestral arthropods. Considering the relative order of the major genes (protein-coding genes and rRNAs), only one or two genes were rearranged with respect to their positions in the ancestral genome. We explored the phylogenetic relationships among the available oribatid mites, and the results confirmed the systematic position of Hermannia in the Crotonioidea superfamily. This was also supported by the synapomorphic gene-derived boundaries. CONCLUSIONS: The tRNA "lost" phenomenon is not universal in oribatid mites. Rather, highly atypical secondary structure of the inferred mt tRNA genes made them unidentifiable using a single type of tRNA search program. The use of multi-software combined with a manual annotation approach can improve the accuracy of tRNA gene annotation. In addition, we identified the precise systematic position of Hermannia and validated that Astigmata is nested in Oribatida.
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Evolución Molecular , Reordenamiento Génico , Genoma Mitocondrial , Ácaros/genética , ARN de Transferencia/genética , Animales , Anotación de Secuencia Molecular , Filogenia , Suelo/parasitologíaRESUMEN
BACKGROUND: Primary thyroid lymphoma (PTL) is a rare thyroid malignancy, there are few large sample studies on PTL and no standardized treatment regimen has been established due to the rarity. The aims of this study were to explore the incidence and prognostic factors of PTL and construct visual prognostic prediction models for post-chemotherapy and postoperative patients. METHODS: The incidence of PTL in 1975-2017 was extracted from the US Surveillance, Epidemiology, and End Results (SEER) database, then assessed using joinpoint regression software. A total of 1616 eligible PTL patients diagnosed in 1998-2016 were brought into prognostic analysis. Multivariate Cox regression analyses were carried out to reveal independent prognostic elements for overall survival (OS) and cancer-specific survival (CSS). RESULTS: PTL incidence showed a relatively steady increase in 1975-1994, which annual percent change (APC) was 4.0%, and steady decreasing in 1994-2017(APC - 2.4%). Age, marital status, lymphoma Ann Arbor stage, histological subtypes, surgery, chemotherapy, and radiation were significantly correlated to OS and CSS. Nomograms were constructed to predict OS and CSS in post-chemotherapy and postoperative PTL patients separately, and were verified to have good reliability. CONCLUSIONS: The incidence of PTL increased and subsequently decreased. We revealed the prognostic implications and constructed reliable nomograms for post-chemotherapy and postoperative PTL patients.
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Antineoplásicos/administración & dosificación , Linfoma/epidemiología , Nomogramas , Vigilancia de la Población/métodos , Cuidados Posoperatorios/métodos , Neoplasias de la Tiroides/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Linfoma/diagnóstico , Linfoma/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Programa de VERF , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Adulto JovenRESUMEN
Over the past two decades, the designs of redox polymers have become critical to the field of mediated bioelectrocatalysis and are used in commercial glucose biosensors, as well as other bioelectrochemical applications (e.g., energy harvesting). These polymers are specifically used to immobilize redox mediators on electrode surfaces, allowing for self-exchange-based conduction of electrons from enzymes far from the electrode to the electrode surface. However, the synthesis of redox polymers is challenging and results in large batch-to-batch variability. Herein, we report a rapid entrapment of mediators for NAD+-dependent bioelectrocatalysis within reverse ionically condensed polyelectrolytes. A high ionic strength aqueous solution of oppositely charged polyelectrolytes, composed of cationic polyguanidinium (PG) chloride and anionic sodium hexametaphosphate (P6), undergoes phase inversion into a solid microporous polyelectrolyte complex (PEC) when introduced into a low ionic strength aqueous solution. The ionic strength-triggered phase inversion of PGP6 solutions was investigated as a means to entrap mediators on the surface of electrodes for mediated bioelectrocatalysis. Compared to the traditional cross-linked immobilizations using redox polymers, this phase inversion takes place within seconds and requires up to 60 min for complete stabilization. In this work, redox mediator phenazine ethosulfate (PES) was entrapped within PGP6 on electrode surfaces for nicotinamide adenine dinucleotide (NAD+)-dependent bioelectrocatalysis. In the bulk solution, NAD+-dependent dehydrogenase enzymes catalyze the oxidation of the substrate while reducing NAD to reduced nicotinamide adenine dinucleotide (NADH). The resulting NADH is reoxidized to NAD+ by the entrapped PES that gets reduced on the electrode, completing the NAD+-regeneration-based bioelectrocatalysis. To show the use of these new materials in an application, biofuel cells were evaluated using four different anodic enzyme systems (alcohol dehydrogenase, lactate hydrogenase, glycerol dehydrogenase, and glucose dehydrogenase).
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NAD/química , Oxidorreductasas/química , Fenazinas/química , Polielectrolitos/química , Biocatálisis , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Enzimas Inmovilizadas/química , Guanidinas/química , Oxidación-Reducción , Fosfatos/químicaRESUMEN
BACKGROUND: The key characteristics in the pathogenesis of nonalcoholic steatohepatitis (NASH) are hepatic lipotoxicity, inflammatory cell infiltration (activated macrophages, in part), and varying degrees of fibrosis. The fatty acid palmitate (PA) can cause hepatocyte cellular dysfunction, but whether and how this process contributes to macrophage-associated inflammation is not well understood. This study aimed to explore whether lipid-injured hepatocytes result in the secretion of osteopontin (sOPN), and how sOPN induces macrophage migration to steatosis hepatocytes. METHODS: Human hepatocellular carcinoma HepG2 cells were incubated with PA to establish the lipotoxicity in hepatocytes model in vitro. The released sOPN was isolated, characterized, and applied to macrophage-like cells differentiated from the human monocytic cell line THP-1 cells. C57BL/6 mice were fed either chow or a diet high in fructose-fat-glucose (FFG) to induce NASH in vivo. Some NASH model mice were also given siSPP1 for two weeks to inhibit the expression of OPN. Related tissues were collected and analyzed by histology, immunofluorescence, ELISA, qRT-PCR, and western blotting. RESULTS: PA upregulated OPN expression and release in human hepatocytes, which drove the migration of macrophages. Incubation of HepG2 cells with palmitate increased mRNA expression and secretion of OPN in cell culture supernatants. Compared with the BSA and siSPP1 groups, treatment with the supernatant derived from PA-treated hepatocytes promoted macrophage migration and activation. The sOPN induction of macrophage migration occurred via CD44 engagement and activation of the pFak-NFκB signaling pathway. Likewise, administration of siSPP1 to NASH mice inhibited the expression and release of OPN, which was associated with decreased liver dysfunction, inflammatory cell infiltration, and even fibrosis. CONCLUSIONS: sOPN, which is released from lipid-injured hepatocytes, emerges as a cytokine driving the migration of macrophages, contributing to an inflammatory response in NASH.
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Movimiento Celular , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Hepatocitos/patología , Receptores de Hialuranos/metabolismo , Lípidos/toxicidad , Macrófagos/metabolismo , FN-kappa B/metabolismo , Osteopontina/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Fosforilación , Transducción de Señal , Células THP-1 , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Bioelectrocatalysis is an interdisciplinary research field combining biocatalysis and electrocatalysis via the utilization of materials derived from biological systems as catalysts to catalyze the redox reactions occurring at an electrode. Bioelectrocatalysis synergistically couples the merits of both biocatalysis and electrocatalysis. The advantages of biocatalysis include high activity, high selectivity, wide substrate scope, and mild reaction conditions. The advantages of electrocatalysis include the possible utilization of renewable electricity as an electron source and high energy conversion efficiency. These properties are integrated to achieve selective biosensing, efficient energy conversion, and the production of diverse products. This review seeks to systematically and comprehensively detail the fundamentals, analyze the existing problems, summarize the development status and applications, and look toward the future development directions of bioelectrocatalysis. First, the structure, function, and modification of bioelectrocatalysts are discussed. Second, the essentials of bioelectrocatalytic systems, including electron transfer mechanisms, electrode materials, and reaction medium, are described. Third, the application of bioelectrocatalysis in the fields of biosensors, fuel cells, solar cells, catalytic mechanism studies, and bioelectrosyntheses of high-value chemicals are systematically summarized. Finally, future developments and a perspective on bioelectrocatalysis are suggested.
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Técnicas Biosensibles , Técnicas Electroquímicas , Catálisis , Electrodos , Oxidación-ReducciónRESUMEN
This contribution describes a synthetic strategy for the fabrication of multicomponent colloidal "molecules" with controllable complex morphologies and compositionally distinct lobes. Using 3-(trimethoxysilyl)propyl methacrylate (TPM) as the building block, the methodology enables a scalable bulk synthesis of customized chiral colloidal particles with geometric and compositional chirality by a sequential seeded growth method. The synthetic protocol presents a versatile platform for constructing colloidal molecules with multiple components having customized shapes and functionalities, with the potential to impact the design of chromatic patchy particles, colloidal swimmers, and chiral optical materials, as well as informing programmable assembly.
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Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancers, but rare in small cell lung cancers (SCLCs). In previous reports, some SCLC patients with EGFR mutations could benefit from EGFR tyrosine kinase inhibitors (TKIs). In this study, we reported a case in which an SCLC patient with EGFR exon 19 deletion (19-Del) mutation did not benefit from EGFR-TKIs. Interestingly, the standard treatment strategies for SCLC also failed to control tumor progression. Moreover, we screened 43 SCLC patients in China and found that the frequency of EGFR mutations in Chinese SCLC patients was about 4.65% by next-generation sequencing (NGS). Collectively, this case illustrated a rare subtype of SCLCs which harbored EGFR mutations and was intrinsically resistant to standard treatments and EGFR-TKIs. We also tried to explore the mechanisms underlying drug resistance. The literature concerning SCLCs with EGFR mutations is reviewed.
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Photo-bioelectrocatalysis combines the natural and highly sophisticated process of photosynthesis in biological entities with an abiotic electrode surface, to perform semi-artificial photosynthesis. However, challenges must be overcome, from the establishment and understanding of the photoexcited electron harvesting process at the electrode to the electrochemical characterization of these biotic/abiotic systems, and their subsequent tuning for enhancing energy generation (chemical and/or electrical). This Feature Article discusses the various approaches utilized to tackle these challenges, particularly focusing on powerful multi-disciplinary approaches for understanding and improving photo-bioelectrocatalysis. Among them is the combination of experimental evidence and quantum mechanical calculations, the use of bioinformatics to understand photo-bioelectrocatalysis at a metabolic level, or bioengineering to improve and facilitate photo-bioelectrocatalysis. Key aspects for the future development of photo-bioelectrocatalysis are presented alongside future research needs and promising applications of semi-artificial photosynthesis.