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Hepatic viral infections and breast cancer (BC) constitute major global health challenges, yet the interconnection between these hepatic infections and BC continues to be ambiguous. Conducting a comprehensive evaluation of the link between hepatitis virus infection and the incidence of BC and leveraging data from the National Health and Nutrition Examination Survey covering the period from 1999 to March 2022, we utilized logistic regression and subgroup analysis, among other methodologies, to execute a cross-sectional investigation. The univariate logistic regression analysis elucidates that individuals classified as non-Hispanic White exhibit a markedly higher incidence of BC at 2.620 (95% confidence interval [CI], 1.117-7.676; Pâ =â .045); moreover, advanced age at 1.063 (95% CI, 1.036-1.093; Pâ <â .001), elevated educational attainment at 1.962 (95% CI, 1.17-3.366; Pâ =â .012), and higher income levels at 2.835 (95% CI, 1.303-7.439; Pâ =â .017) emerge as significant predisposing factors for BC. In contrast, a greater number of live births significantly diminishes the risk of BC, reducing the incidence to 81.1% with each additional birth. Pertaining to hepatitis and vaccination status, our analysis distinctly demonstrates that only hepatitis B at 0.110 (95% CI, 0.018-0.353; Pâ =â .002) bears a significant inverse relationship with BC risk, suggesting a protective effect. The multivariate logistic regression analysis further reveals a negative association between hepatitis B infection and BC incidence, whereas hepatitis B vaccination shows a positive correlation with the disease incidence. After adjusting for all covariates, model 3 delineates odds ratios (95% CI) as follows: 0.14 (0.02-0.50; Pâ =â .009) and 1.92 (0.99-3.62; Pâ =â .046). Our investigation uncovers that within the general populace, there exists an inverse correlation between hepatitis B infection and BC incidence; in addition, the administration of the hepatitis B virus vaccine is potentially positively associated with the prevalence of BC.
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Neoplasias de la Mama , Hepatitis B , Encuestas Nutricionales , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Incidencia , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Estudios Transversales , Factores de Riesgo , Modelos Logísticos , AncianoRESUMEN
Herein, a magnetic cationic Schiff base polymeric material (Fe3O4@SiO2-Schiff-TAPB-DA) was fabricated simply and rapidly, which was explored as a magnetic adsorbent for magnetic solid-phase extraction (MSPE) for enriching seven avermectins insecticides in surface water and milk matrices combined with ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Under the optimized pretreatment and instrumental parameters, the analytes showed good linearity in the range of 0.5-200.0 ng·mL-1 with a correlation coefficient (R2) greater than 0.9990 and high precision. The limits of detection for the analytes were 0.004-0.047 µg·L-1 for surface water sample and 0.008-0.250 µg·kg-1 for milk samples. Satisfactory recoveries of spiked target compounds were in the range of 82.25- 100.87 % for surface water sample and 72.73- 119.62 % for milk samples. The results indicated powerfully Fe3O4@SiO2-Schiff-TAPB-DA was of significant potential as an MSPE adsorbent for the detection of avermectin insecticides in surface water and milk, which provides a quick and efficient idea for enriching avermectins insecticides in complicated matrices.
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Insecticidas , Ivermectina , Límite de Detección , Leche , Bases de Schiff , Extracción en Fase Sólida , Espectrometría de Masas en Tándem , Leche/química , Animales , Bases de Schiff/química , Ivermectina/análogos & derivados , Ivermectina/análisis , Ivermectina/aislamiento & purificación , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodos , Insecticidas/análisis , Insecticidas/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Dióxido de Silicio/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Polímeros/químicaRESUMEN
BACKGROUND: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. METHODS: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. RESULTS: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. CONCLUSIONS: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.
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Inflamación , MAP Quinasa Quinasa Quinasa 5 , Microglía , Proteínas Quinasas p38 Activadas por Mitógenos , Microglía/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , MAP Quinasa Quinasa Quinasa 5/genética , Animales , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Ratones , Inflamación/metabolismo , Línea Celular , Sistema de Señalización de MAP Quinasas , Humanos , Transducción de SeñalRESUMEN
Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.
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Ameloblastoma , Descompresión Quirúrgica , Imagenología Tridimensional , Mandíbula , Tomografía Computarizada por Rayos X , Humanos , Ameloblastoma/cirugía , Ameloblastoma/diagnóstico por imagen , Femenino , Masculino , Mandíbula/cirugía , Mandíbula/diagnóstico por imagen , Adulto , Descompresión Quirúrgica/métodos , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven , Adolescente , Persona de Mediana Edad , Neoplasias Mandibulares/cirugía , Neoplasias Mandibulares/diagnóstico por imagen , Desarrollo Óseo , Regeneración ÓseaRESUMEN
We study the effect of electrolytes on the stability in aqueous media of spherical lignin particles (LP) and its relevance to Pickering emulsion stabilization. Factors considered included the role of ionic strength on morphology development, LP size distribution, surface charge, interfacial adsorption, colloidal and wetting behaviors. Stable emulsions are formed at salt concentrations as low as 50 mM, with the highest stability observed at a critical concentration (400 mM). We show salt-induced destabilization of LP aqueous dispersions at an ionic strength >400 mM. At this critical concentration LP flocculation takes place and particulate networks are formed. This has a profound consequence on the stability of LP-stabilized Pickering emulsions, affecting rheology and long-term stability. The results along with quartz microgravimetry and confocal microscopy observations suggest a possible mechanism for stabilization that considers the interfacial adsorption of LP at oil/water interfaces. The often-unwanted colloidal LP destabilization in water ensues remarkably stable Pickering emulsions by the effect of network formation.
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Coloides , Emulsiones , Lignina , Agua , Emulsiones/química , Lignina/química , Coloides/química , Agua/química , Floculación , Concentración Osmolar , Adsorción , Sales (Química)/química , Reología , Tamaño de la PartículaRESUMEN
Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4+ T cells, CD8+ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4+ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.
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Neoplasias Colorrectales , Proteómica , Humanos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Proteómica/métodos , Masculino , Femenino , Sistema Inmunológico/metabolismo , Persona de Mediana Edad , Anciano , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/inmunologíaRESUMEN
This study focuses on enhancing the strength and water stability of paper straws through a novel approach involving a binary emulsion of lignin-based polyurethane and chitosan. Kraft lignin serves as the raw material for synthesizing a blocked waterborne polyurethane, subsequently combined with carboxylated chitosan to form a stable binary emulsion. The resulting emulsion, exhibiting remarkable stability over at least 6 months, is applied to the base paper. Following emulsion application, the paper undergoes torrefaction at 155 °C. This process deblocks isocyanate groups, enabling their reaction with hydroxyl groups on chitosan and fibers, ultimately forming ester bonds. This reaction significantly improves the mechanical strength and hydrophobicity of paper straws. The composite paper straws demonstrate exceptional mechanical properties, including a tensile strength of 47.21 MPa, Young's modulus of 4.33 GPa, and flexural strength of 32.38 MPa. Notably, its water stability is greatly enhanced, with a wet tensile strength of 40.66 MPa, surpassing commercial paper straws by 8 folds. Furthermore, the composite straw achieves complete biodegradability within 120 days, outperforming conventional paper straws in terms of environmental impact. This innovative solution presents a promising and sustainable alternative to plastic straws, addressing the urgent need for eco-friendly products.
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Quitosano , Emulsiones , Lignina , Papel , Poliuretanos , Resistencia a la Tracción , Poliuretanos/química , Quitosano/química , Lignina/química , Emulsiones/química , Agua/química , Biodegradación Ambiental , Fenómenos Mecánicos , Interacciones Hidrofóbicas e Hidrofílicas , Módulo de ElasticidadRESUMEN
Birinapant, an antagonist of the inhibitor of apoptosis proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the mechanism remains elusive. Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.
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Presentación de Antígeno , Dipéptidos , Indoles , Masculino , Animales , Humanos , Terapia Combinada , Modelos Animales de EnfermedadRESUMEN
The rheological properties of a substance depend greatly on its morphology, and rod-shaped cellulose nanocrystals (RCNCs) and cellulose nanofibrils (CNFs) have been extensively studied for their rheological properties. Nevertheless, the rheological properties of disc-shaped cellulose nanocrystals (DCNCs) with crystalline allomorph II derived from mercerized cellulose remain unknown yet. This work investigated the DCNCs' rheological properties in depth using steady-shear and oscillation measurements. At the same concentration, DCNC's suspension viscosity is lower than that of RCNC; RCNC has an instinct viscosity of 258.2, while DCNC has 187.9. Comparing RCNC suspensions with cellulose nanorods, DCNC has a lower aspect ratio and exhibits a distinct steady shear behavior. Under polarized film, DCNC suspension cannot self-assemble into chiral or liquid crystal phases, and with increasing concentrations, the system transitions from an isotropic phase to a gel phase. Oscillation sweeps demonstrate that the gel transition occurs at 7 %-8 %. Based on thixotropic recovery sweep outcomes, the high-stress oscillations enhance the network structure of DCNC suspensions, which is significantly different from that of RCNC suspensions. Results demonstrate the unique properties of DCNC, highlighting its application as a rheological modifier.
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Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.
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Rationale: Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells. It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood. In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs. Methods: In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells. TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells. Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization. RNA-seq was performed to explore the genes regulated by CREPT during field cancerization. Results: CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway. Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT. Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway. CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. Conclusion: CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.
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Vesículas Extracelulares , Neoplasias , Humanos , Línea Celular Tumoral , Proteómica , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/genética , Proteínas de Neoplasias/genética , Vesículas Extracelulares/metabolismo , Neoplasias/genéticaRESUMEN
The rapid and accurate detection of miRNAs is of great significance for early diagnosis and treatment of cancer. Hence, a novel enzyme-free and label-free electrochemical biosensor based on bio-barcode amplification for detecting miRNAs was presented. Sandwich structures constructed of magnetic nanoparticles modified with DNA probes, gold nanoparticles with numerous barcoded DNA strands that hybridized with target miRNAs were fabricated as the amplifier. The released barcoded DNA strands then acted as the secondary targets and triggered the electrochemical sensor with a significant electrochemical response. A highly sensitive (detection limit of 0.24 fM) and selective electrochemical miRNA detection was realized, which has great potential for application in miRNA-related clinical diagnosis and biochemical research.
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Técnicas Biosensibles , Nanopartículas del Metal , MicroARNs , MicroARNs/genética , Oro/química , Nanopartículas del Metal/química , ADN/química , Técnicas Electroquímicas , Límite de DetecciónRESUMEN
The properties of cellulose nanocrystals with allomorph II (CNC-II) vary with the sources and the treatments received. In this work, the influences of hydrolysis time, temperature, and the applied acid concentration on the crystal size of CNC-II were investigated by the surface response experimental design. The results showed that temperature was the most significant factor affecting the crystal size of CNC-II during hydrolysis from mercerized cellulose. Then the morphology and colloidal properties of CNC-II were revealed by dynamic laser scattering (DLS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), etc. XRD results indicated that CNC-II had slightly lower crystallinity (80.89 % vs 82.7 %) and larger crystallite size (5.21 vs. 5.13 nm) than CNC-I. TEM and AFM results showed that the morphology of CNC-II were disc-like and rod-like particles, with an average diameter of 14.6 ± 4.7 nm (TEM) and a thickness of 4- 8 nm (AFM). TG and XPS revealed the reduced thermal stability was due to the introduced sulfate groups in CNC-II during hydrolysis. This investigation has addressed the features of CNC-II derived from mercerized cellulose, and it would be promising in fabricating advanced materials.
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Celulosa , Nanopartículas , Hidrólisis , Celulosa/química , Nanopartículas/química , TemperaturaRESUMEN
Metastasis leads to a high mortality rate in colorectal cancer (CRC). Increased neutrophil extracellular traps (NETs) formation is one of the main causes of metastasis. However, the mechanism of NETs-mediated metastasis remains unclear and effective treatments are lacking. In this study, we found neutrophils from CRC patients have enhanced NETs formation capacity and increased NETs positively correlate with CRC progression. By quantitative proteomic analysis of clinical samples and cell lines, we found that decreased secreted protein acidic and rich in cysteine (SPARC) results in massive NETs formation and integrin α5ß1 is the hub protein of NETs-tumor cell interaction. Mechanistically, SPARC regulates the activation of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) pathway by interacting with the receptor for activated C kinase 1 (RACK1). Over-activated NADPH oxidase generates more reactive oxygen species (ROS), leading to the release of NETs. Then, NETs upregulate the expression of integrin α5ß1 in tumor cells, which enhances adhesion and activates the downstream signaling pathways to promote proliferation and migration. The combination of NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and integrin α5ß1 inhibitor ATN-161 (Ac-PHSCN-NH2) effectively suppresses tumor progression in vivo. Our work reveals the mechanistic link between NETs and tumor progression and suggests a combination therapy against NETs-mediated metastasis for CRC.
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Neoplasias Colorrectales , Trampas Extracelulares , Humanos , Trampas Extracelulares/metabolismo , NADPH Oxidasas/metabolismo , Integrina alfa5beta1/metabolismo , Osteonectina/metabolismo , Proteómica , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Colorrectales/patologíaRESUMEN
Low-protein (LP) diets extend the lifespan of diverse species and are associated with improved metabolic health in both rodents and humans. Paradoxically, many athletes and bodybuilders consume high-protein (HP) diets and protein supplements, yet are both fit and metabolically healthy. Here, we examine this paradox using weight pulling, a validated progressive resistance exercise training regimen, in mice fed either an LP diet or an isocaloric HP diet. We find that despite having lower food consumption than the LP group, HP-fed mice gain significantly more fat mass than LP-fed mice when not exercising, while weight pulling protected HP-fed mice from this excess fat accretion. The HP diet augmented exercise-induced hypertrophy of the forearm flexor complex, and weight pulling ability increased more rapidly in the exercised HP-fed mice. Surprisingly, exercise did not protect from HP-induced changes in glycemic control. Our results confirm that HP diets can augment muscle hypertrophy and accelerate strength gain induced by resistance exercise without negative effects on fat mass, and also demonstrate that LP diets may be advantageous in the sedentary. Our results highlight the need to consider both dietary composition and activity, not simply calories, when taking a precision nutrition approach to health.
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Dieta Rica en Proteínas , Entrenamiento de Fuerza , Humanos , Animales , Ratones , Control Glucémico , Cadherinas , HipertrofiaRESUMEN
Objective: Doppler-derived myocardial performance index (Tei) has been used in the evaluation of right ventricular (RV) function. However, the usage in isolated diastolic dysfunction is limited.We sought to find a new Tei'-index that is more appropriate for evaluating isolated diastolic dysfunction (IDD) based on the symmetry of cardiac structure and function. Methods: 21 patients with impaired RV relaxation were compared to 44 control subjects. Tei and Tei' including their components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), the ejection time (ET), and RV rapid filling time (RFT) were measured from RV outflow and tricuspid inflow Doppler velocity profiles. Results: Tei-index have no change between IDD group and control subjects (0.21 ± 0.08 vs 0.23 ± 0.07 P[bond, double bond]NS). The Tei'-index was significantly shortened in IDD group(0.24 ± 0.09 vs 0.32 ± 0.12,pï¼0.05).The decrease in Tei'-index was due to the prolongation of both IRT and RFT, and in the abbreviation of ICT. Tei'-index cutoff value of ≥0.31 identified impaired RV relaxation with a sensitivity of 50 % and specificity of 86 %.We also find that the Tei'-index correlated well with doppler measures of diastolic parameters like E/A, E/e', DT, which suggests its potential use as a noninvasive indicator of the right ventricular (RV) relaxation in patients with heart failure of different causes. Conclusion: New Tei's index is highly effective and specific in the evaluation of early diastolic dysfunction of right ventricle, and can be used as an indicator for the detection of IDD in clinic.
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Many cancers harbor homologous recombination defects (HRDs). A HRD is a therapeutic target that is being successfully utilized in treatment of breast/ovarian cancer via synthetic lethality. However, canonical HRD caused by BRCAness mutations do not prevail in liver cancer. Here we report a subtype of HRD caused by the perturbation of a proteasome variant (CDW19S) in hepatitis B virus-bearing (HBV-bearing) cells. This amalgamate protein complex contained the 19S proteasome decorated with CRL4WDR70 ubiquitin ligase, and assembled at broken chromatin in a PSMD4Rpn10- and ATM-MDC1-RNF8-dependent manner. CDW19S promoted DNA end processing via segregated modules that promote nuclease activities of MRE11 and EXO1. Contrarily, a proteasomal component, ADRM1Rpn13, inhibited resection and was removed by CRL4WDR70-catalyzed ubiquitination upon commitment of extensive resection. HBx interfered with ADRM1Rpn13 degradation, leading to the imposition of ADRM1Rpn13-dependent resection barrier and consequent viral HRD subtype distinguishable from that caused by BRCA1 defect. Finally, we demonstrated that viral HRD in HBV-associated hepatocellular carcinoma can be exploited to restrict tumor progression. Our work clarifies the underlying mechanism of a virus-induced HRD subtype.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Neoplasias Hepáticas/genética , Transactivadores/genética , Transactivadores/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Factores de Transcripción/genética , Hepatitis B/genética , Recombinación Homóloga , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
The ability to measure the in vivo rate of protein degradation is a major limitation in numerous fields of biology. Here, we present a protocol for quantifying this rate in mice using a pulse-chase technique that utilizes an azide-bearing non-canonical amino acid called azidohomoalanine (AHA). We describe steps for using chow containing AHA to pulse-label the animal's proteome. We then detail the quantification of AHA-labeled proteins in whole-tissue lysates or histological sections using a copper-catalyzed azide-alkyne cycloaddition 'click' reaction. For complete details on the use and execution of this protocol, please refer to Steinert et al. (2023).1.
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Aminoácidos , Azidas , Ratones , Animales , Proteolisis , Azidas/química , Proteoma , Alquinos/químicaRESUMEN
Nanocellulose (NC) is the desired building block for novel biomaterials. The morphology of NC is one of the core parameters impacting the functionality and property of engineered functional materials. This work aims to reveal the relationship between the product morphology and sulfuric acid hydrolysis conditions (including acid concentration, temperature and time), and to realize morphological regulation of obtained NC. Three representative products were obtained from microcrystalline cellulose via sulfuric acid hydrolysis, which are cellulose nanocrystals with broad size distribution (W-CNC, 383.9 ± 131.7 nm in length, 6 ± 2.1 nm in height) obtained by 61 % H2SO4, 55 °C and 90 min, cellulose nanospheres (CNS, 61.3 ± 15.9 nm in diameter) obtained by 64 % H2SO4, 35 °C and 75 min, and CNC with narrow size distribution (N-CNC, 276.1 ± 28.7 nm in length, 4.1 ± 0.6 nm in height), obtained by 64 % H2SO4, 45 °C and 45 min. The results showed that the crystallographic form of W-CNC and N-CNC are cellulose I, while cellulose I and II coexist in CNS. Only W-CNC and N-CNC can form chiral nematic structures through evaporation-induced self-assembly strategy and reflected light with specific wavelengths. In addition, the formation mechanism of CNS with cellulose I/II was proposed, which provided a better understanding of NC morphology regulation.
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A complete understanding of the associations of ambient air pollution with prevalence of pulmonary nodule is lacking. We aimed to investigate the associations of ambient air pollutants with prevalence of pulmonary nodule. A total of 9991 health examination participants was enrolled and 3166 was elected in the final in Shijiazhuang between April 1st, 2018, and December 31st, 2018. 107 participants were diagnosed in pulmonary nodule while 3059 participants were diagnosed in non-pulmonary (named control). The individual exposure of participants was evaluation by Empirical Bayesian Kriging model according to their residential or work addresses. The pulmonary nodules were found and diagnosed by health examination through chest x-ray detection. Our results suggested that there were positive associations between prevalence of pulmonary nodules and PM2.5 (OR = 1.06, 95% CI: 1.02, 1.11) as well as O3 (OR = 1.49, 95% CI: 1.35, 1.66) levels. The platelet count (PLT) acted as the mediator of pulmonary nodules related with the PM2.5 exposure, while the neutrophil-to-lymphocyte ratio (NLR) as well as platelet-to-lymphocyte ratio (PLR) were the mediators of pulmonary nodules related with the O3 exposure. This study suggests that long-term exposure to PM2.5 and O3 may significantly associated with prevalence of pulmonary nodules, and the above associations are mediated by PLT, NLR and PLR.