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Although BRCA1/2 mutations are not commonly found in small cell lung cancer (SCLC), a substantial fraction of SCLC shows clinically relevant response to PARP inhibitors (PARPis). However, the underlying mechanism(s) of PARPi sensitivity in SCLC is poorly understood. We performed quantitative proteomic analyses and identified proteomic changes that signify PARPi responses in SCLC cells. We found that the vulnerability of SCLC to PARPi could be explained by the degradation of lineage-specific oncoproteins (e.g., ASCL1). PARPi-induced activation of the E3 ligase HUWE1 mediated the ubiquitin-proteasome system (UPS)-dependent ASCL1 degradation. Although PARPi induced a general DNA damage response in SCLC cells, this signal generated a cell-specific response in ASCL1 degradation, leading to the identification of HUWE1 expression as a predictive biomarker for PARPi. Combining PARPi with agents targeting these pathways markedly improved therapeutic response in SCLC. The degradation of lineage-specific oncoproteins therefore represents a previously unidentified mechanism for PARPi efficacy in SCLC.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteína BRCA1/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteómica , Proteína BRCA2/genética , Proteínas Oncogénicas , Línea Celular Tumoral , Proteínas Supresoras de Tumor , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Background: Diabetic nephropathy (DN) is a common kidney disease in diabetic patients. Long non-coding RNA maternally expressed gene 3 (MEG3) and microRNA (miR)-23c are reported to be implicated in DN development. Nevertheless, it is unclear that the molecular mechanism between MEG3 and miR-23c in DN remains unclear. Methods: Human mesangial cells (HMCs) were treated with high glucose (HG) to simulate the DN status in vitro. Expression of MEG3 and miR-23c was measured. Effects of MEG3 silencing on HG-stimulated HMC injury were determined. The relationship between MEG3 and miR-23c was verified by the dual-luciferase reporter and RNA immunoprecipitation assays. Results: MEG3 was overexpressed in serums from DN patients and HG-stimulated HMCs. MEG3 knockdown weakened HG-stimulated HMC proliferation, extracellular matrix (ECM) accumulation, and inflammation. MEG3 regulated lin-28 homolog B (LIN28B) expression through adsorbing miR-23c. MiR-23c inhibitor reversed MEG3 knockdown-mediated effects on HG-stimulated HMC proliferation, ECM accumulation, and inflammation. LIN28B overexpression overturned miR-23c mimic-mediated effects on HG-stimulated HMC proliferation, ECM accumulation, and inflammation. Conclusion: MEG3 regulated HMC injury via regulation of the miR-23c/LIN28B axis in DN, which can help us better understand the mechanism of DN mediated by MEG3.
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Recent studies have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). We identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response. Upon sensing genotoxicity, RNF114 was recruited, in a PAR-dependent manner, to DNA lesions, where it targeted PARP1 for degradation. The blockade of this pathway interfered with the removal of PARP1 from DNA lesions, leading to profound PARP1 trapping. We showed that a natural product, nimbolide, inhibited the E3 ligase activity of RNF114 and thus caused PARP1 trapping. However, unlike conventional PARPi, nimbolide treatment induced the trapping of both PARP1 and PARylation-dependent DNA repair factors. Nimbolide showed synthetic lethality with BRCA mutations, and it overcame intrinsic and acquired resistance to PARPi, both in vitro and in vivo. These results point to the exciting possibility of targeting the RNF114-PARP1 pathway for the treatment of homologous recombination-deficient cancers.
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Neoplasias , Mutaciones Letales Sintéticas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/genética , ADN , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi-omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed (DE) proteins, including 119 upregulated and 241 downregulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and extracellular matrix (ECM)-receptor interactions. Additionally, a protein-protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data and identified a total of 1077 DE genes. Pathways enriched by the DE genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune-related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/genética , Pólipos Nasales/complicaciones , Rinitis/diagnóstico , Rinitis/genética , Rinitis/complicaciones , Proteómica , Sinusitis/genética , Sinusitis/complicaciones , Sinusitis/metabolismo , Enfermedad CrónicaRESUMEN
To study the diversity of microbial flora in Hongqu sufu and analyze the characteristics of special flavor compounds, this study took self-made Hongqu sufu as the research object. Dynamic changes in sufu during fermentation were studied. High-throughput sequencing (HTS) was used to analyze changes in the diversity of fungal and bacterial communities during fermentation. The results showed that at the phylum level, the dominant fungal phyla were identified, Mucormyces and Ascomycetes. The dominant bacterial phyla were Proteobacteria and Firmicutes. At the genus level, the dominant fungal genera were identified as Actinomucor, Monascus, and Aspergillus. The dominant bacterial genera were Pseudomonas, Aneurimibacillus, Sphingobacterium, and Bacillus. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with technology that can dynamically change flavor compounds was explored to investigate the correlation between microbiota and flavor compounds. In different stages of fermentation, 75 main volatile organic compounds were identified, including seven alcohols, four acids, 16 alkanes, 14 olefins, seven kinds of aldehydes, two kinds of ketones, 10 kinds of esters, one kind of phenol, one kind of sulfur-containing compound, one benzene, and 12 other compounds. The correlation analysis between flora and flavor compounds showed that the fungi genera Alternaria and Pichia were significantly correlated with most flavor compounds. Bacteria genera including Weissella, Hafnia-Obesumbacterium, and Leuconostoc had a strong positive correlation with ethyl oleate.
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In this work, the overall adsorption kinetic process of hydroquinone on Phragmites australis biochar (PAC) was analyzed in depth. A 3D mass transfer model of pore volume and surface diffusion was established, and the diffusion mechanism was analyzed. The characterization results show PAC has a higher porosity value, which is conducive to the adsorption of hydroquinone. The adsorption process modeling results show that the combined effect of pore volume diffusion and surface diffusion promotes the total diffusion process of hydroquinone in the PAC particles, and the two mechanisms of pore volume and surface diffusion exist simultaneously. Under the different operating concentrations, the range of surface diffusion coefficient Ds is 2.5 × 10-10-1.74 × 10-9 cm2/s, and the contribution rate of surface diffusion SDCP% is close to 100%, which is much larger than pore volume diffusion, revealing that regardless of the contact time and position, surface diffusion occupies the main position in intraparticle diffusion.
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In this study, high-throughput technology was used to reveal the core microbial community in sorghum-based fermented grains during different fermentation periods and to quantify the impacts of physicochemical parameters and microbial interspecies relationships on the volatile flavors. Headspace solid-phase microextraction, coupled with gas chromatography-mass spectrometry, was used to select 14 major volatile products with relative content greater than 1% in at least one sample, including three alcohols, one acid, eight esters, and two alkanes. The relative content of alkanes was only high on the first day and continued to decrease during the later fermentation stage. As fermentation progressed, the relative content of ethanol, ethyl acetate (aroma), and isoamyl alcohol (pungent, spicy) first increased and then decreased. In addition, the relative content of other ethyl esters continued to increase. In the early stage of fermentation (1-7 days), the temperature, moisture, and alcohol content showed an upward trend, while the content of reducing sugar decreased. As the temperature decreased in the middle and later stages (7-28 days), the physicochemical parameters tended to stabilize. In community composition, the dominant bacterial genera were Lactobacillus, Streptomyces, and Acetobacter, and the fungal genera were mainly Issatchenkia, Torulaspora, and Pichia. Network analysis identified a total of 10 core microbiota as the main contributors of esters and alkane metabolites. Moreover, total acidity and reducing sugar played important roles in promoting the formation of core microbiota and succession of dominant taxa.
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The use of the black soldier fly has been demonstrated to be effective in the treatment of swine manure. Since the outbreaks of ASFV, prevention procedures, including manure disinfection, have changed dramatically. Glutaraldehyde (GA) and potassium peroxymonosulfate (PPMS) have been shown to be effective in the prevention of this pathogen and are thus widely used in the disinfection of swine manures, etc. However, research on the effects of disinfectants in manures on the growth of BSFL and gut microbiota is scarce. The goal of this study was to determine the effects of GA and PPMS on BSFL growth, manure reduction, and gut microbiota. In triplicate, 100 larvae were inoculated in 100 g of each type of manure compound (manure containing 1% GA treatment (GT1), manure containing 0.5% GA treatment (GT2), manure containing 1% PPMS treatment (PT1), manure containing 0.5% PPMS treatment (PT2), and manure without disinfectant (control)). After calculating the larval weight and waste reduction, the larval gut was extracted and used to determine the microbial composition. According to the results, the dry weights of the larvae fed PT1-2 (PT1: 86.7 ± 4.2 mg and PT2: 85.3 ± 1.3 mg) were significantly higher than those of the larvae fed GT1-2 (GT1: 72.5 ± 2.1 mg and GT2: 70 ± 2.8 mg) and the control (64.2 ± 5.8 mg). There was a 2.8-4.03% higher waste reduction in PT1-2 than in the control, and the waste reduction in GT1-2 was 7.17-7.87% lower than that in the control. In a gut microbiota analysis, two new genera (Fluviicola and Fusobacterium) were discovered in PT1-2 when compared to GT1-2 and the control. Furthermore, the disinfectants did not reduce the diversity of the microbial community; rather, Shannon indices revealed that the diversities of GT1-2 (GT1: 1.924 ± 0.015; GT2: 1.944 ± 0.016) and PT1 (1.861 ± 0.016) were higher than those of the control (1.738 ± 0.015). Finally, it was found that both disinfectants in swine manures at concentrations of 1% and 0.5% may be beneficial to the complexity and cooperation of BSFL gut microbiota, according to an analysis of microbial interactions.
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To explore the influence of the crystal structure difference of melamine trimetaphosphate (MAP) on the application performance of its polymer composites, an intumescent flame retardant with the optimal crystal type was designed and synthesized to improve the mechanical properties and flame retardancy of polyamide 6 (PA6). I-MAP and II-MAP were obtained using different concentrations of MA and sodium trimetaphosphate (STMP) in an acidic aqueous solution. The morphology, chemical composition, and thermal stability were comprehensively characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The dispersion, mechanical properties, and flame retardancy of PA6/I-MAP and PA6/II-MAP were evaluated by SEM, stress and strain, limiting oxygen index test (LOI), vertical burning test (UL-94), cone calorimetry (CONE) test, and char residue analysis. The conclusion is as follows: I-MAP and II-MAP have a greater influence on the physical properties of PA6 but less influence on the chemical properties. Compared with PA6/I-MAP, the tensile strength of PA6/II-MAP is 104.7% higher, the flame rating reaches V-0, and PHRR is reduced by 11.2%.
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Livestock manure is an important component of agricultural organic waste, and in recent years, with the development of research on the bioconversion of manure, BSFs have been proven to be useful in the treatment of a variety of livestock wastes. In-depth research on the composition of manure and its effect on the development of BSFL is, however, very scarce. The purpose of this study was to identify the parameters that influenced the growth of BSFL that was fed fattening pig manure. The pH, moisture, and nutrients of the fattening manures (namely, nursery, growing, and finishing pig manures) were measured. To examine the influence of manure types on larval growth, 100 larvae were inoculated in 100 g of each type of manure in triplicate. According to the findings, larvae fed finishing pig manure had the lowest dry weight (30.2 ± 6.1 mg) compared to those fed growing (58.2 ± 7.3 mg) or nursery (65.5 ± 6.2 mg) pig manure. The correlation coefficients (r) between the nutrients in the manure and the weight of the larvae were calculated. Hemicellulose had the greatest |r| value (0.9569). Further research revealed that larvae raised on hemicellulase-pretreated finishing pig manure frequently weighed 21-30% (days 2-8) more than larvae raised on control manure. In conclusion, hemicellulose was a significant component that might hinder larval growth. The results of this study could be used to improve the system before it is put into use.
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BACKGROUND: Growth differentiation factor-10 (GDF-10), a member of the TGF-ß superfamily, plays a crucial role in cell proliferation and differentiation. In some tumors, GDF-10 can act as a tumor suppressor to inhibit tumor progression, but its role in posterior squamous cell carcinoma has not been reported yet. METHODS: The aim of this study was to investigate the effect of GDF-10 on the epithelial-mesenchymal transition of laryngeal squamous cell carcinoma, and to provide new ideas for future targets in the treatment of laryngeal squamous carcinoma. RESULTS: The effect of GDF-10 on tumor growth was detected; bioinformatics analysis was performed to predict the downstream targets of GDF-10, and RT-PCR and western blot were performed to detect the expression levels of target genes and proteins, respectively. CONCLUSION: Our findings support that GDF-10 can inhibit the proliferation, migration, and invasion, and promote apoptosis of laryngeal carcinoma AMC-HN-8 cells. GDF-10 inhibits the EMT of laryngeal carcinoma through LRP4 and thus inhibits the progression of laryngeal carcinoma.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Factor 10 de Diferenciación de Crecimiento/genética , Factor 10 de Diferenciación de Crecimiento/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Factor de Crecimiento Transformador beta/metabolismo , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Inguinal lymphadenectomy (iLAD) is effective for penile carcinoma treatment, but usually results in many complications. This study aims to clinically evaluate the feasibility and clinical significance of a laparoscopic radical iLAD approach partly preserving great saphenous vein branches for penile carcinoma patients. METHODS: A total of 48 patients with penile cancer who underwent laparoscopic radical iLAD with retention of the great saphenous vein in Henan Cancer Hospital from 2012 Jan to 2020 Dec were included in this study. Sixteen penile carcinoma patients who underwent laparoscopic radical iLAD preserving parts of superficial branches of the great saphenous vein were identified as the sparing group, and the matched 32 patients who incised those branches were identified as control group. This new procedure was performed by laparoscopy, preserving parts of superficial branches of the great saphenous vein, superficial lateral and medial femoral veins. Clinicopathological features and perioperative variables were recorded. Postoperative complications, including skin flap necrosis, lymphorrhagia, and lower extremity edema were analyzed retrospectively. RESULTS: We found that the operative time of the sparing group is significantly longer than the control group (p = 0.011). There was no statistical difference in intraoperative blood loss, the lymph node number per side, average time to remove the drainage tube and postoperative hospital stay between the two groups. Compared to the control group, the sparing group showed a significantly decreased incidence of lower extremity edema (p = 0.018). The preservation of parts of superficial branches of the great saphenous vein was mainly decreased the incidence of edema below ankle (p = 0.034). CONCLUSIONS: This study demonstrated that the iLAD with preserving parts of superficial branches of the great saphenous vein, with a decreased incidence of postoperative complications, is a safe and feasible approach for penile cancer.
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Carcinoma , Laparoscopía , Neoplasias del Pene , Carcinoma/cirugía , Vena Femoral/patología , Humanos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Neoplasias del Pene/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Vena Safena/patología , Vena Safena/cirugíaRESUMEN
To achieve the requirements of modified bismaleimide resin composites in electronic industry and high energy storage devices, flame retardancy, water resistance and dielectric properties must be improved. Hence, a highly efficient multifunctional graphene nanoplatelets hybrid flame retardant is prepared by ionic liquid graphite and ammonium polyphosphate. The preparation processes of the flame retardants are simple, low energy consumption and follow the green chemical concept of 100% utilization of raw materials, compared with chemical stripping. The bismaleimide resin containing 10 wt.% of the flame retardant show good flame retardancy, resulting in the limiting oxygen index increases to above 43%, and the peak heat release rate, total heat release and total smoke release decrease by 41.8%, 47.8% and 52.3%, respectively. After soaking, mass loss percentage of the modified bismaleimide resin only decreases by 0.96%, the dielectric constant of the composite increases by 39.4%, and the dielectric loss decreases with the increase of frequency. The hybrid flame retardants show multifunctional effect in the modified bismaleimide resin, due to the physical barrier, the chemical char-formation, hydrophobicity and strong conductivity attributed to co-work of Graphene nanoplatelets, ammonium polyphosphate and ionic liquid.
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Retaining nitrogen for polyacrylonitrile (PAN) based carbon anode is a cost-effective way to make full use of the advantages of PAN for sodium-ion batteries (SIBs). Here, a simple strategy has been successfully adopted to retain N atoms inâ situ and increase production yield of a novel composite PAZ by mixing 3â wt % of zinc borate (ZB) with poly (acrylonitrile-co-itaconic acid) (PANIA). Among the prepared carbonised fibre (CF) samples, PAZ-CF-700 maintains the highest N content, retaining 90 % of the original N from PANIA. It represents the highest capacity storage contribution (80.55 %) and the lowest impedance Rct (117â Ω). Consequently, the specific capacity increases from 60â mAh g-1 of PANIA-CF-700 to 190â mAh g-1 of PAZ-CF-700 at a current density of 100â mA g-1 . At the same time, PAZ-CF-700 exhibits a good rate performance and excellent long-term cycling stability with a specific capacity of 94â mAh g-1 after 4000 cycles at 1.6â A g-1 .
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Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.
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Antígenos CD36/metabolismo , Endocitosis/fisiología , Ácidos Grasos/metabolismo , Lipoilación , Células 3T3-L1 , Aciltransferasas/metabolismo , Adipocitos/metabolismo , Animales , Antígenos CD36/deficiencia , Antígenos CD36/genética , Caveolas/metabolismo , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Humanos , Gotas Lipídicas/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Obesidad/tratamiento farmacológico , Fosforilación , Transducción de Señal , Quinasa Syk/antagonistas & inhibidores , Quinasa Syk/metabolismo , Aumento de Peso/efectos de los fármacos , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/metabolismoRESUMEN
Objective: Mitotic arrest-deficient protein 1 (MAD1) is a kinetochore protein essential for the mitotic spindle checkpoint. Proteomic studies have indicated that MAD1 is a component of the DNA damage response (DDR) pathway. However, whether and how MAD1 might be directly involved in the DDR is largely unknown. Methods: We ectopically expressed the wild type, or a phosphorylation-site--mutated form of MAD1 in MAD1 knockdown cells to look for complementation effects. We used the comet assay, colony formation assay, immunofluorescence staining, and flow cytometry to assess the DDR, radiosensitivity, and the G2/M checkpoint. We employed co-immunoprecipitation followed by mass spectrometry to identify MAD1 interacting proteins. Data were analyzed using the unpaired Student's t-test. Results: We showed that MAD1 was required for an optimal DDR, as knocking down MAD1 resulted in impaired DNA repair and hypersensitivity to ionizing radiation (IR). We found that IR-induced serine 214 phosphorylation was ataxia-telangiectasia mutated (ATM) kinase-dependent. Mutation of serine 214 to alanine failed to rescue the phenotypes of MAD1 knockdown cells in response to IR. Using mass spectrometry, we identified a protein complex mediated by MAD1 serine 214 phosphorylation in response to IR. Among them, we showed that KU80 was a key protein that displayed enhanced interaction with MAD1 after DNA damage. Finally, we showed that MAD1 interaction with KU80 required serine 214 phosphorylation, and it was essential for activation of DNA protein kinases catalytic subunit (DNA-PKcs). Conclusions: MAD1 serine 214 phosphorylation mediated by ATM kinase in response to IR was required for the interaction with KU80 and activation of DNA-PKCs.
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Proteínas de la Ataxia Telangiectasia Mutada/deficiencia , Proteínas de Ciclo Celular/metabolismo , Daño del ADN/genética , Proteína Quinasa Activada por ADN/metabolismo , Autoantígeno Ku/metabolismo , Animales , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Daño del ADN/efectos de la radiación , Proteína Quinasa Activada por ADN/genética , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células HCT116 , Células HeLa , Humanos , Autoantígeno Ku/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mutación , Fosforilación , Tolerancia a Radiación/genética , Radiación Ionizante , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A zeolite imidazole framework (ZIF-67) was assembled onto the surface of ammonium polyphosphate (APP) for preparing a series multifunctional flame-retardant APP-ZIFs. The assembly mechanism, chemical structure, chemical compositions, morphology, and specific surface area of APP-ZIFs were characterized. The typical APPZ1 and APPZ4 were selected as intumescent flame retardants with dipentaerythritol (DPER) because of their superior unit catalytic efficiency of cobalt by thermogravimetric analysis. APPZ1 and APPZ4 possessed 6.8 and 92.1 times the specific surface area of untreated APP, which could significantly enhance the interfacial interaction, mechanical properties, and migration resistance when using in ethylene-vinyl acetate (EVA). With 25% loading, 25% APPZ4/DPER achieved a limiting oxygen index value of 29.4% and a UL 94 V-0 rating, whereas 25% APP/DPER achieved a limiting oxygen index value of only 26.2% and a V-2 rating, respectively. The peak of the heat release rate, smoke production rate, and CO production rate respectively decreased by 34.7%, 39.0%, and 40.1%, while the char residue increased by 91.7%. These significant improvements were attributed to the catalytic graphitization by nano cobalt phosphate and the formation of a more protective char barrier comprised of graphite-like carbon.
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OBJECTIVES: The study summarizes the effectiveness of ultrasound-assisted microsurgical left spermatic-inferior epigastric vein anastomosis for treating nutcracker syndrome (NCS)-associated varicocele. METHODS: Cases of NCS-associated varicocele were recruited between December 2012 and December 2018. Prior to the operation, all patients were tested for the internal diameter and blood flow velocity of left renal vein, testicular volume, maximum venous diameter and venous retrograde flow in the pampiniform plexus of veins during the Valsalva maneuver by Color Doppler ultrasound. Moreover, the direction of left spermatic and inferior epigastric vein was marked. RESULTS: All patients underwent ligation of the internal spermatic veins and left spermatic-inferior epigastric vein anastomosis under microscopy. Color Doppler ultrasound, urinary and semen analysis (above age 18 years old) were reviewed during the follow-up period. 53 patients (94.6%) underwent spermatic-inferior epigastric vein anastomosis with the mean operation time of 78.4 ± 14.2 min. The hospital stay was 4-7 days. Scrotal hydrocele, wound infection and testicular atrophy did not occur after operation. However, there were 5 cases of left varicocele recurrence and 2 cases of vascular anastomotic thrombosis. 51 cases had decrease in blood peak flow rate of left renal vein and improvement in nutcracker syndrome while scrotal bulge symptoms resolved in 26 cases. 10 cases had microscopic hematuria disappearance with symptom improvement in 2 cases. 19 cases of left testicular hypotrophy experience no further deterioration after surgery, of which 16 cases had catch-up testicular growth. CONCLUSION: Ultrasound-assisted microsurgical left spermatic-inferior epigastric vein anastomosis assisted is safe, easy and effective for treating nutcracker syndrome-associated varicocele.
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Microcirugia , Cirugía Asistida por Computador , Ultrasonografía Doppler en Color , Ultrasonografía Intervencional , Varicocele/diagnóstico por imagen , Varicocele/cirugía , Adolescente , Anastomosis Quirúrgica/métodos , Niño , Humanos , Masculino , Estudios Prospectivos , Síndrome de Cascanueces Renal/complicaciones , Testículo/irrigación sanguínea , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Varicocele/etiología , Procedimientos Quirúrgicos Vasculares/métodos , Venas , Adulto JovenRESUMEN
Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4-/- and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.
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Aciltransferasas/metabolismo , Antígenos CD36/metabolismo , Ácidos Grasos/metabolismo , Lipoilación , Proteínas de la Membrana/metabolismo , Células 3T3-L1 , Tejido Adiposo/metabolismo , Secuencia de Aminoácidos , Animales , Transporte Biológico , Membrana Celular/metabolismo , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , TransfecciónRESUMEN
Alginates (nickel alginate, NiA; copper alginate, CuA; zinc alginate, ZnA) and 3-aminopropyltriethoxysilane (APTES) were alternately deposited on a magnesium hydroxide (MH) surface by the spray-drying-assisted layer-by-layer assembly technique, fabricating some efficient and environmentally benign flame retardants (M-FR, including Ni-FR, Cu-FR, and Zn-FR). The morphology, chemical compositions, and structures of M-FR were investigated. With 50 wt % loading, compared with EVA28+MH, the peak heat release rate, smoke production rate, and CO production rate of EVA28+Ni-FR decreased by 50.78%, 61.76%, and 66.67%, respectively. The metals or metal oxide nanoparticles arising from alginates could catalyze the pyrolysis intermediates of EVA into graphene and amorphous carbon, which could bind the inorganic compounds (the decomposition products of MH and APTES) together and form some more protective barriers. For each M-FR, the flame retardant and smoke suppression efficiency were different, which were caused by the diverse carbonization and graphitization behaviors of three alginates. ZnA generated some ZnO aggregations and could not catalyze the graphitization of intermediates. For CuA, the catalytic graphitization was limited by the tightly binding graphene layer. As for NiA, the configuration of the Ni atom could not provide strong binding of Ni substrate and carbon. The liquid-like Ni nanoparticles could restructure and get out from firm graphene shells, so the catalytic graphitization of NiA was efficient and sustainable. This work displayed the catalytic graphitization mechanism of alginates while exploring a simple and novel strategy for fabricating efficient green flame retardants.