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Undifferentiated spermatogonia are composed of a heterogeneous cell population including spermatogonial stem cells (SSCs). Molecular mechanisms underlying the regulation of various spermatogonial cohorts during their self-renewal and differentiation are largely unclear. Here we show that AKT1S1, an AKT substrate and inhibitor of mTORC1, regulates the homeostasis of undifferentiated spermatogonia. Although deletion of Akt1s1 in mouse appears not grossly affecting steady-state spermatogenesis and male mice are fertile, the subset of differentiation-primed OCT4+ spermatogonia decreased significantly, whereas self-renewing GFRα1+ and proliferating PLZF+ spermatogonia were sustained. Both neonatal prospermatogonia and the first wave spermatogenesis were greatly reduced in Akt1s1-/- mice. Further analyses suggest that OCT4+ spermatogonia in Akt1s1-/- mice possess altered PI3K/AKT-mTORC1 signaling, gene expression and carbohydrate metabolism, leading to their functionally compromised developmental potential. Collectively, these results revealed an important role of AKT1S1 in mediating the stage-specific signals that regulate the self-renewal and differentiation of spermatogonia during mouse spermatogenesis.
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Proteínas Proto-Oncogénicas c-akt , Espermatogonias , Masculino , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Testículo/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Espermatogénesis/genética , Diferenciación Celular/fisiología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismoRESUMEN
In this work, an advanced hybrid material was constructed by incorporating niobium pentoxide (Nb2O5) nanocrystals with nitrogen-doped carbon (NC) derived from ZIF-8 dodecahedrons, serving as a support, referred to as Nb2O5/NC. Pt nanocrystals were dispersed onto Nb2O5/NC using a simple impregnation reduction method. The obtained Pt/Nb2O5/NC electrocatalyst showed high oxygen reduction reaction (ORR) activity due to three-phase mutual contacting structure with well-dispersed Pt and Nb2O5NPs. In addition, the conductive NC benefits electron transfer, while the induced Nb2O5can regulate the electronic structure of Pt element and anchor Pt nanocrystals, thereby enhancing the ORR activity and stability. The half-wave potential (E1/2) for Pt/Nb2O5/NC is 0.886 V, which is higher than that of Pt/NC (E1/2= 0.826 V). The stability examinations demonstrated that Pt/Nb2O5/NC exhibited higher electrocatalytic durability than Pt/NC. Our work provides a new direction for synthesis and structural design of precious metal/oxides hybrid electrocatalysts.
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Type 2 diabetes mellitus (T2DM) has a major comorbidity known as diabetes-associated cognitive dysfunction (DACD). Studies have demonstrated that the gut microbiota is crucial in mediating the cognitive abnormalities that occur in diabetic individuals. Additionally, changes in dietary fatty acid intake levels, inflammatory cytokines, and microRNAs (miRs) have an effect on cognitive performance. However, further studies are needed to identify the link between gut microbiota and cognition in T2DM patients and the role that the above indicators play in this process. In order to provide a new rationale for the treatment of cognitive dysfunction in diabetes, this study was conducted in the middle-aged and elderly Beijing population to examine the differences in gut microbiota between DACD and T2DM patients as well as to further explore the role of erythrocyte membrane fatty acids, inflammatory cytokines, and miRs in gut microbiota-mediated cognitive impairment. According to the results, the abundance of norank_f_Eubacterium_coprostanoligenes_group, Acidaminococcus, Enterorhabdus, and norank_f_Clostridium_methylpentosum_group was higher in DACD patients compared to T2DM patients at the genus level. Compared with T2DM patients, plasma interleukin-12 (IL-12) concentrations were significantly higher in DACD patients than in T2DM patients, and IL-12 was significantly positively correlated with norank_f_Eubacterium_coprostanoligenes_group. In addition, plasma miR-142-5p was significantly positively correlated with Enterorhabdus and norank_f_Eubacterium_coprostanoligenes_group. We therefore hypothesize that cognitive impairment in T2DM patients is associated with altered gut microbial composition and that the effect of microbiota on cognition may be mediated through IL-12 and miR-142-5p. KEY POINTS: ⢠Type 2 diabetes with or without cognitive impairment differs in gut microbiota. ⢠Differential genera of gut microbiota were associated with inflammatory cytokines. ⢠Differential genera of gut microbiota were associated with plasma microRNAs.
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Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , MicroARNs , Persona de Mediana Edad , Anciano , Humanos , MicroARNs/genética , Diabetes Mellitus Tipo 2/complicaciones , Citocinas , Disfunción Cognitiva/complicaciones , Ácidos Grasos , Interleucina-12RESUMEN
Hyperthermophilic pretreatment composting (HPC) has the advantages of enhanced composting efficiency and accelerated humic substance (HS) over conventional composting (CC). However, the mechanisms towards the accelerated humification process by HPC are still not clear. By means of sterilization technology, the roles of abiotic and biotic components on the formation of HS can be distinguished. The study investigated the humification degree and the succession of microbial community during HPC of pig manure. The mechanisms underlying the accelerated humification by HPC was identified using gamma sterilization. Results showed that HS content increased significantly by 13.72% in HPC and 29.93% in sterilized HPC inoculated with 1% CC (HPC_I), compared with 8.76% increase in CC and 7.12% increase in sterilized CC inoculated with 1% HPC during composting (CC_I). Compared with CC and CC_I, stronger intensities of HA-like and fulvic acid-like components were observed in HPC and HPC_I. Results showed that physicochemical properties, especially pH, were the key factors in accelerating the humification in HPC, while both physicochemical properties and microbial community contributed to the HA formation in CC. The study contributed to a better understanding of the mechanism towards the accelerated humification degree in HPC.
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Compostaje , Animales , Archaea , Sustancias Húmicas , Concentración de Iones de Hidrógeno , Estiércol , Suelo/química , PorcinosRESUMEN
Intratumor heterogeneity (ITH) of T cell receptor (TCR) repertoire in different T-cell subsets and locations in lung adenocarcinomas was unclear. Here, we investigated percentages and TCR repertoire of freshly isolated CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor centers and margins by flow cytometry on 80 tumor samples from 20 patients and high-throughput TCR sequencing on 27 and 25 samples of CD4+ and CD8+ TILs from seven patients. Our results demonstrated that amount and TCR repertoire diversity of CD4+ TILs were significantly higher than those of CD8+ TILs and moreover substantial ITH regarding amount and TCR repertoire of CD4+ and CD8+ TILs were observed. Additionally, ITH of CD4/CD8 T-cell ratio and CD8+ TIL repertoire across center regions was lower than that across margin regions. The amount and TCR repertoire ITH of CD4+ and CD8+ TILs and mean clonality of CD8+ TILs in tumor centers were associated with relapse. Our study provides insights into amount and TCR repertoire ITH of CD4+ and CD8+ TILs in tumor centers and margins as well as corresponding association with prognosis in lung adenocarcinoma patients, suggesting potential clinical significance of TCR repertoire.
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Adenocarcinoma/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Neoplasias Pulmonares/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Receptores de Antígenos de Linfocitos T/metabolismo , Análisis de SupervivenciaRESUMEN
Recent successes in tumour immunotherapies have highlighted the importance of tumour immunity. However, most previous studies to date have focused on T-cell immune response, although B cells are key players in the core immune network and are associated with T-cell immune response. Based on our previous study delineating T-cell receptor (TCR) repertoire in seven patients with oesophageal squamous cell carcinoma (ESCC), this study profiled the B-cell receptor (BCR) repertoire of multiple tumour regions, adjacent normal tissue, and blood from the same seven patients to reveal the characteristics of B-cell immunity and the relationship to TCR repertoire in ESCC patients. We found that intratumour BCR repertoire was significantly more oligoclonal than matched adjacent normal tissue or peripheral blood and, moreover, clonal amplification of B cells in multiple tumour regions was significantly heterogeneous, although clonal amplification of the TCR repertoire across different tissue compartments and regions of the same tumour was similar. However, both BCR and TCR repertoires in the tumour microenvironment were distinct from those in adjacent normal tissues and blood, and thus represented a group of B and T cells that were spatially confined to the tumour microenvironment and could react to tumour antigens. Additionally, B- and T-cell clones varying between different tumour regions showed intratumour heterogeneity of B- and T-cell immune response. Thus, multiple tumour biopsies could be essential to comprehensively delineate the adaptive immune response to an individual ESCC. These findings expand our understanding of adaptive anti-tumour immunity and shed more light on ESCC immunotherapy. This study provides insights into the intratumour heterogeneity of the BCR repertoire as well as the difference and relationship between the BCR and TCR repertoire in ESCC, expanding our understanding of adaptive anti-tumour immunity and ESCC immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Inmunidad Adaptativa , Linfocitos B/inmunología , Neoplasias Esofágicas/inmunología , Carcinoma de Células Escamosas de Esófago/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Linfocitos T/inmunología , Microambiente Tumoral , Anciano , Linfocitos B/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Receptores de Antígenos de Linfocitos B/genética , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal , Linfocitos T/metabolismoRESUMEN
OBJECTIVES: Experimental studies suggested that bisphenol A (BPA) exposure increased the risk of metabolic syndrome (MetS) through the mechanism of insulin resistance. All previous epidemiological studies of BPA and MetS were cross-sectional studies, and their findings were mixed. This study aims to provide further evidence on the association between urinary BPA and risk of MetS using a prospective cohort study in China. METHODS: The study population was from the Shenzhen Night shift workers' cohort. A total of 1227 male workers were recruited from the baseline survey in 2013 and then followed until 2017. Modified Adult Treatment Panel III criteria were used to identify the cases of MetS. Urinary BPA concentration was assessed using high-performance liquid chromatography-tandem mass spectrometry, and it was categorised into three subgroups by tertiles to obtain the adjusted HR (aHR) and 95% CI using Cox proportional hazard model. RESULTS: During 4 years of follow-up, 200 subjects developed MetS. Compared with the lowest urinary BPA subgroup, a weakly increased risk of MetS was suggested among those with the middle (aHR=1.19, 95% CI 0.87 to 1.63) and high level of urinary BPA (aHR=1.16, 95% CI 0.84 to 1.59); however, the significant association with MetS was restricted primarily to the smokers, showing a positive gradient with urinary BPA (middle level: aHR=2.40, 95% CI 1.13 to 5.08; high level: aHR=2.87, 95% CI 1.38 to 5.98; p trend=0.010). CONCLUSION: This prospective cohort study provided further evidence that exposure to BPA may increase the risk of MetS, and this association was further positively modified by cigarette smoking.
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Compuestos de Bencidrilo/orina , Síndrome Metabólico/epidemiología , Fenoles/orina , Adulto , China/epidemiología , Fumar Cigarrillos , Estudios de Cohortes , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The feather-degrading strain Thermoactinomyces sp. YT06 secretes an extracellular keratinolytic protease (KERTYT); however, the gene encoding this protease remains unknown. The kerT1 gene (1170 bp) encoding keratinase was cloned and expressed in Escherichia coli BL21(DE3). Purified recombinant keratinase (rKERTYT) was achieved at a yield of 39.16% and 65.27-fold purification with a specific activity of 1325 U/mg. It was shown that rKERTYT has many similarities to the native enzyme (KERTYT) by characterization of rKERTYT. The molecular weight of rKERTYT secreted by recombinant E. coli was approximately 28 kDa. The optimal temperature and the pH values of rKERTYT were 65 °C and 8.5, respectively, and the protein remained stable from 50 to 60 °C and pH 6-11. The keratinase was strongly inhibited by phenyl methane sulfonyl fluoride (PMSF), suggesting that it belongs to the serine protease family. It was significantly activated by Mn2+ and ß-mercaptoethanol (ß-Me). rKERTYT showed stability and retained over 80% activity with the existence of organic solvents such as acetone, methylbenzene and dimethyl sulfoxide. These findings indicated that rKERTYT will be a promising candidate for the enzymatic processing of keratinous wastes.
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Clonación Molecular , Escherichia coli/metabolismo , Expresión Génica , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Thermoactinomyces/enzimología , Activadores de Enzimas/análisis , Inhibidores Enzimáticos/análisis , Estabilidad de Enzimas , Escherichia coli/genética , Concentración de Iones de Hidrógeno , Peso Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Temperatura , Thermoactinomyces/genéticaRESUMEN
Soil weakness across consecutive cropping fields can be partially explained by the changes in microbial community diversity and structure. Succession patterns and co-occurrence mechanisms of bacteria and fungi, especially beneficial or pathogenic memberships in continuous cropping strawberry fields and their response to edaphic factors remained unclear. In this study, Illumina sequencing of bacterial 16S ribosomal RNA and fungal internal transcribed spacer genes was applied in three time-course (1, 5, and 10 years) fields across spring and winter. Results showed that the richness and diversity of bacterial and fungal communities increased significantly (p < 0.05) in 1-year field and decreased afterwards across two seasons. Network analysis revealed beneficial bacterial and fungal genus (Bacillus and Trichoderma) dominated under 1-year field whereas Fusarium accumulated under 10-year field at either season. Moreover, Trichoderma harzianum and Bacillus subtilis that have been reported to effectively control Fusarium wilt in strawberries accumulated significantly under 1-year field. Canonical correspondence analysis showed that beneficial bacterial Rhodospirillales and Rhizobiales and fungal Glomerales accumulated in 1-year field and their distributions were significantly affected by soil pH, microbial biomass C (MBC), and moisture. On the contrary, fungal pathogenic species Fusarium oxysporum strongly increased under 10-year field at the winter sample and the abundance was positively (p < 0.01) correlated with soil moisture. Our study suggested that the potential of microcosm under 1-year field stimulates the whole microbial diversity and favors different beneficial taxa across two seasons. Soil pH, moisture, and MBC were the most important edaphic factors leading to contrasting beneficial and pathogenic memberships across consecutive strawberry cropping fields.
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Fenómenos Fisiológicos Bacterianos , Biodiversidad , Fragaria/microbiología , Hongos/fisiología , Microbiología del Suelo , Bacterias/clasificación , ADN Espaciador Ribosómico/genética , Hongos/clasificación , Filogenia , ARN Ribosómico 16S/genética , Estaciones del Año , Factores de TiempoRESUMEN
The effects of hydraulic retention time (20 and 15 days) and swine manure to rice straw ratios on distribution of sulfonamides (SAs) in liquid and solid anaerobic digestates were studied using bench-scale completely stirred tank reactors at (37 ± 1) °C. Results showed that anaerobic digestion (AD) treatment exhibited a good removal effect on sulfadiazine (SDZ), sulfadimidine (SM2) and sulfachloropyridazine (SCP), especially at HRT = 20 days and co-digestion with swine manure and rice straw. The removal rates of SDZ and SM2 were more than 90%, but only 72.8% for SCP. The residual SAs were mainly remained in solid digestates, with residual rates ranging from 28.8% to 71.3%, 40.6% to 88.0, and 82.7% to 97.0% for SDZ, SM2 and SCP, respectively. Due to lower pKa and higher log K ow of SCP, its residue in solid digestates was far more than SDZ and SM2. Higher HRT and co-digestion could improve the degradation of SAs, which can also be put down to the occurrence of cometabolism of SAs and COD.
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Estiércol/microbiología , Oryza/química , Sulfonamidas/química , Anaerobiosis , Animales , PorcinosRESUMEN
This paper aimed to reveal the degradation behavior of a new type of biodegradable containers. The biodegradable containers, which was made of modified soybean adhesive and straw, was processed in situ biodegradation under natural condition. The physicochemical property and microstructure of straw nursery containers treated and untreated were characterized with Cellulose Tester, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope - Energy Dispersive X-ray Spectroscopy (SEM-EDS), and Thermo-gravimetry Analysis (TGA), respectively. The results indicated that the content of cellulose, hemicellulose and lignin of treated specimen decreased to 21.43%, 21.41% and 9.54% from 29.03%, 30.44% and 12.52%, respectively, comparing with those of untreated straw nursery container. FTIR analysis revealed that the ester and fat bond have been ruptured, and the aromatic characteristic peak became weakened. SEM-EDS spectrum showed the microfibril chain in the container has been fragmentation, and the soybean adhesive was also degradation. The surface of container appeared oxidization degradation. TGA analysis showed that a large number of small molecules have been produced in the process of degradation and the thermo-stability of treated samples improved.
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The Cancer/Testis Antigen (CTA), Prostate-associated Gene 4 (PAGE4), is a stress-response protein that is upregulated in prostate cancer (PCa) especially in precursor lesions that result from inflammatory stress. In cells under stress, translocation of PAGE4 to mitochondria increases while production of reactive oxygen species decreases. Furthermore, PAGE4 is also upregulated in human fetal prostate, underscoring its potential role in development. However, the proteins that interact with PAGE4 and the mechanisms underlying its pleiotropic functions in prostatic development and disease remain unknown. Here, we identified c-Jun as a PAGE4 interacting partner. We show that both PAGE4 and c-Jun are overexpressed in the human fetal prostate; and in cell-based assays, PAGE4 robustly potentiates c-Jun transactivation. Single-molecule Förster resonance energy transfer experiments indicate that upon binding to c-Jun, PAGE4 undergoes conformational changes. However, no interaction is observed in presence of BSA or unilamellar vesicles containing the mitochondrial inner membrane diphosphatidylglycerol lipid marker cardiolipin. Together, our data indicate that PAGE4 specifically interacts with c-Jun and that, conformational dynamics may account for its observed pleiotropic functions. To our knowledge, this is the first report demonstrating crosstalk between a CTA and a proto-oncogene. Disrupting PAGE4/c-Jun interactions using small molecules may represent a novel therapeutic strategy for PCa.
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Antígenos de Neoplasias/metabolismo , Próstata/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Activación Transcripcional , Regiones no Traducidas 3'/genética , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Línea Celular Tumoral , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Transferencia Resonante de Energía de Fluorescencia , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Mutación , Próstata/embriología , Próstata/crecimiento & desarrollo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica , Conformación Proteica , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-jun/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estrés FisiológicoRESUMEN
Human hepatocellular carcinoma HepG2 Cell line were cultured with different concentrations of excretory/secretory proteins from Trichinella spiralis, and MTT assay was used to evaluate the cell inhibition rate. After co-cultured with 300 µg/ml excretory/secretory proteins for 24 h, the HepG2 cells were observed under a fluorescence microscope with AO and EB staining. When co-cultured with 75 µg/ml excretory/secretory proteins for 24 h, the HepG2 cells were quantified by flow cytometry using Annexin V-FITC/PI stain, and the expression of cleaved-caspase 9 was detected by immunofluorescence assay. The proliferation of HepG2 cells was inhibited significantly by excretory/secretory proteins in a dosage dependant manner. Under fluorescence microscope, some HepG2 cells presented typical apoptotic morphologic changes and the cleaved-caspase 9 protein expression was higher than that of the control. The early and late apoptotic cells and necrotic ones occupied 17.9%, 7.3%, and 6.6%, respectively.
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Proliferación Celular , Trichinella spiralis , Animales , Citometría de Flujo , Células Hep G2 , HumanosRESUMEN
PURPOSE: We report cancer specific outcomes of micropapillary nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 36 cases restaged within 3 months of the initial diagnosis of micropapillary nonmuscle invasive bladder cancer. Early radical cystectomy within a 3-month landmark after restaging transurethral bladder tumor resection or conservative treatment with intravesical bacillus Calmette-Guérin, surveillance or deferred radical cystectomy was offered according to surgeon and patient preference. The cumulative incidence of cancer specific mortality and metastasis was estimated using the Kaplan-Meier method. Differences in the cumulative incidence of cancer specific mortality and metastasis between the groups were tested using the log rank test. RESULTS: Median patient age was 68 years (IQR 63-77). The male-to-female ratio was 3:1. At restaging all patients had cT1 disease or less. Early radical cystectomy was performed in 15 patients (42%) while 21 (58%) underwent conservative treatment. Median followup after landmark in cancer specific survivors was 3.1 years (IQR 1.1-5.9). The 5-year cumulative incidence of cancer specific mortality was 17% in the early radical cystectomy group and 25% in the conservative management group for an absolute difference of 7% (95% CI -26-41, p = 0.8). The 5-year cumulative incidence of metastasis was 21% and 34%, respectively, with an absolute difference of 13% (95% CI -23-49, p = 0.9). The extent of the micropapillary component was not significantly associated with cancer specific mortality (p = 0.4) or metastasis (p = 0.9). CONCLUSIONS: Using proper selection criteria, including patient and pathological factors, certain patients in whom cT1 micropapillary urothelial carcinoma was managed conservatively did not have significantly worse outcomes than patients treated with early radical cystectomy.
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Adyuvantes Inmunológicos/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Cistectomía , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Background and Objective: Cognitive dysfunction is highly prevalent in obese people, and food is a key factor in obesity, and dietary inflammatory index (DII) can reflect whether diet has anti-inflammatory or pro-inflammatory potential. In addition, dietary fatty acid consumption is linked to inflammation, obesity, and cognitive impairment. Erythrocyte membrane fatty acids can reflect dietary fatty acid intake. Our hypothesis was that erythrocyte membrane fatty acids might have a significant impact on the relationship between DII and cognition in obese individuals, and we designed experiments to test the hypothesis. Methods: In three villages in Beijing, we collected 579 respondents from individuals 45 to 75 years old and categorized them by body mass index. The Montreal Cognitive Assessment (MoCA) score and DII score was calculated and gas chromatography was used to measure the proportion of erythrocyte membrane fatty acids. The relationship between the DII score and cognition was examined using multiple linear regression and binary logistic regression. Mediation analysis can help to understand the causal chain between variables, deeply explore the internal relationship and mechanism of action between variables. So a multiple chain mediation model was developed to investigate the mediating factors between the DII score and cognitive association. Results: According to adjusted linear regression, higher DII scores were linked to lower MoCA scores in the obese group. The negative correlation between DII score and cognitive function score remains in binary linear regression. We discovered through mediation analysis that erythrocyte membrane fatty acids mediate the detrimental link between DII and cognitive function in obese individuals. Conclusion: We propose that higher DII scores in obese people are associated with a decline in cognitive function. In addition, this effect might be mediated via the fatty acids in the erythrocyte membrane.
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Chronic inflammation is a major risk factor for cancer. Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, ultimately leading to a breakdown of intestinal barrier function. Clematis florida var. plena is a folk prescription used to treat inflammation and rheumatism in She pharmacy. The bioactivity of C. florida var. plena is primarily due to triterpene saponins. Huzhangoside C (HZ) is an active component of C. florida var. plena. In this study, the anti-inflammatory effect of HZ on a mouse colitis model induced by dextran sulfate sodium (DSS) was investigated. Result indicated a notable reduction in body weight loss and colon length shortening in HZ-mediated mice compared to DSS-stimulated control mice. Furthermore, inflammatory signaling mechanisms involving interleukin-6 and tumor necrosis factor-α were suppressed in HZ-treated mice. HZ treatment significantly suppressed the expression of nuclear factor kappa B (NF-κB), STAT3, and iNOS in colon tissue. After HZ treatment, malondialdehyde and nitric oxide levels were significantly decreased, while Nrf-2, superoxide dismutase, and glutathione expression levels were notably improved. The result indicated that HZ could activate the Nrf-2 signal cascade, inhibit the expression of NF-κB, eNOS, and STAT3, and enhance the intestinal barrier function of DSS stimulated ulcerative colitis intestinal injury. The results suggest that HZ is potential anti-inflammatory agent for treating IBD.
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Colitis Ulcerosa , Colitis , Enfermedades Inflamatorias del Intestino , Sulfatos , Humanos , Animales , Ratones , FN-kappa B/metabolismo , Dextranos/efectos adversos , Dextranos/metabolismo , China , Etnicidad , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Enfermedades Inflamatorias del Intestino/metabolismo , Inflamación/metabolismo , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Colon , Modelos Animales de EnfermedadRESUMEN
This study investigated the effects of different aeration intensities on organic matter (OM) degradation, greenhouse gas emissions (GHG) as well as humification during plant residue composting. Three intermittent aeration intensities of 0.084 (Tlow), 0.19 (Tmedium) and 0.34 (Thigh) L min-1kg-1 DM with 30â min on/30â min off were conducted on a lab-scale composting experiment. Results showed that OM mineralization in Thigh was more evident than Tlow and Tmedium, resulting in the highest humic acid content. Humic acid content in Tmedium and Thigh was 15.7% and 18.5% higher than that in Tlow. The average O2 concentration was 4.9%, 9.5% and 13.6% for Tlow, Tmedium and Thigh. Compared with Tmedium and Thigh, Tlow reduced CO2 and N2O emissions by 18.3%-39.6% and 72.4%-63.9%, but the CH4 emission was highest in Tlow. But the total GHG emission was the lowest in Thigh. Linear Discriminant Analysis Effect Size analysis showed that the core bacteria within Tlow mainly belonged to Anaerolineaceae, which was significantly negatively correlated to the emission of CH4. Thermostaphylospora, Unclassified_Vicinamibacteraceae and Sulfurifustis were identified as core bacteria in Tmedium and Thigh, and these genus were significantly postively correlated to CO2 and N2O emissions. Redundancy analysis showed that total orgnic carbon, O2 and electrical conductivity were the key factors affecting the evolution of bacterial community.
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The importance of renewable resources and environmentally friendly materials has grown globally in recent time. Hemicellulose is renewable lignocellulosic materials that have been the subject of substantial valorisation research. Due to its distinctive benefits, including its wide availability, low cost, renewability, biodegradability, simplicity of chemical modification, etc., it has attracted increasing interest in a number of value-added fields. In this review, a systematic summarizes of the structure, extraction method, and characterization technique for hemicellulose-based materials was carried out. Also, their most current developments in a variety of value-added adsorbents, biomedical, energy-related, 3D-printed materials, sensors, food packaging applications were discussed. Additionally, the most recent challenges and prospects of hemicellulose-based materials are emphasized and examined in-depth. It is anticipated that in the near future, persistent scientific efforts will enable the renewable hemicellulose-based products to achieve practical applications.
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BACKGROUND: Dietary fat intake affects brain composition and function. Different types of dietary fatty acids alter species and abundance of brain lipids in mice. The aim of this study is to explore whether the changes are effective through gut microbiota. METHODS: In our study, 8-week-old male C57BL/6 mice were randomly divided into 7 groups and fed with high-fat diet (HFD) with different fatty acid compositions, control (CON) group, long-chain saturated fatty acid (LCSFA) group, medium-chain saturated fatty acid (MCSFA) group, n-3 polyunsaturated fatty acid (n-3 PUFA) group, n-6 polyunsaturated fatty acid (n-6 PUFA) group, monounsaturated fatty acid (MUFA) group and trans fatty acid (TFA) group. Then, the fecal microbiota transplant (FMT) was performed in other pseudo germ-free mice after antibiotic treatment. The experimental groups were orally perfused with gut microbiota that induced by HFD with different types of dietary fatty acids. The mice were fed with regular fodder before and after FMT. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to analysis the composition of fatty acids in the brain of HFD-fed mice and hippocampus of mice treated with FMT which was collected from HFD-fed mice. RESULTS: The content of acyl-carnitines (AcCa) increased and lysophosphatidylgylcerol (LPG) decreased in all kinds of HFD groups. phosphatidic acids (PA), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents were significantly increased in the n-6 PUFA-fed HFD group. The HFD elevated the saturation of brain fatty acyl (FA). Lysophosphatidylcholine (LPC), lysodi-methylphosphatidylethanolamine (LdMePE), monolysocardiolipin (MLCL), dihexosylceramides (Hex2Cer), and wax ester (WE) significantly increased after LCSFA-fed FMT. MLCL reduced and cardiolipin (CL) raised significantly after n-3 PUFA-fed FMT. CONCLUSIONS: The study revealed, HFD and FMT in mice had certain effects on the content and composition of fatty acids in the brain, especially on glycerol phospholipid (GP). The change of AcCa content in FA was a good indicator of dietary fatty acid intake. By altering the fecal microbiota, dietary fatty acids might affect brain lipids.
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MED19, a component of the mediator complex and a co-regulator of the androgen receptor (AR), is pivotal in prostate cancer cell proliferation. MED19 has two isoforms: a full-length "canonical" and a shorter "alternative" variant. Specific antibodies were developed to investigate these isoforms. Both exhibit similar expression in normal prostate development and adult prostate tissue, but the canonical isoform is elevated in prostate adenocarcinomas. Overexpression of canonical MED19 in LNCaP cells promotes growth under conditions of androgen deprivation in vitro and in vivo, mirroring earlier findings with alternative MED19-overexpressing LNCaP cells. Interestingly, alternative MED19 cells displayed strong colony formation in clonogenic assays under conditions of androgen deprivation, while canonical MED19 cells did not, suggesting distinct functional roles. These isoforms also modulated gene expression differently. Canonical MED19 triggered genes related to extracellular matrix remodeling while suppressing those involved in androgen-inactivating glucuronidation. In contrast, alternative MED19 elevated genes tied to cell movement and reduced those associated with cell adhesion and differentiation. The ratio of MED19 isoform expression in prostate cancers shifts with the disease stage. Early-stage cancers exhibit higher canonical MED19 expression than alternative MED19, consistent with canonical MED19's ability to promote cell proliferation under androgen deprivation. Conversely, alternative MED19 levels were higher in later-stage metastatic prostate cancer than in canonical MED19, reflecting alternative MED19's capability to enhance cell migration and autonomous cell growth. Our findings suggest that MED19 isoforms play unique roles in prostate cancer progression and highlights MED19 as a potential therapeutic target for both early and late-stage prostate cancer.