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Multiclass classification problems are often addressed by decomposing them into a set of binary classification tasks. A critical step in this approach is the effective aggregation of predictions from each decomposed binary classifier to yield the final multiclass prediction, a process known as decoding. Existing studies have ignored the varying generalization ability of each binary classifier across different samples during decoding, potentially leading to suboptimal performance. In this article, we propose an instance-specific loss-weighted (ILW) decoding strategy that gauges the generalization ability of each binary classifier for one specific sample based on its neighboring samples. This estimated generalization ability is then used to adjust the importance of the binary classifier in determining the sample's final prediction. Experimental results validate the effectiveness of the ILW decoding strategy. Furthermore, we demonstrate that softmax regression can be reinterpreted as a one-versus-rest (OvR) decomposition-based multiclass classification algorithm, enabling the application of our decoding strategy to enhance its performance. Comparative studies clearly demonstrate the superiority of the improved softmax regression over its traditional counterpart.
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Modifying cells with polymers on the surface can enable them to gain or enhance function with various applications, wherein the atom transfer radical polymerization (ATRP) has garnered significant potential due to its biocompatibility. However, specifically initiating ATRP from the cell surface for in-situ modification remains challenging. This study established a bacterial surface-initiated ATRP method and further applied it for enhanced Cr(VI) removal. The cell surface specificity was facilely achieved by cell surface labelling with azide substrates, following alkynyl ATRP initiator specifically anchoring with azide-alkyne click chemistry. Then, the ATRP polymerization was initiated from the cell surface, and different polymers were successfully applied to in-situ modification. Further analysis revealed that the modification of Shewanella oneidensis with poly (4-vinyl pyridine) and sodium polymethacrylate improved the heavy metal tolerance and enhanced the Cr(VI) removal rate of 2.6 times from 0.088 h-1 to 0.314 h-1. This work provided a novel idea for bacterial surface modification and would extend the application of ATRP in bioremediation.
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Biodegradación Ambiental , Cromo , Polimerizacion , Shewanella , Shewanella/metabolismo , Cromo/química , Cromo/metabolismo , Química Clic , Azidas/química , Polímeros/química , Polímeros/metabolismo , Ácidos Polimetacrílicos/químicaRESUMEN
BACKGROUND: The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear. AIM: To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population. METHODS: To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity. RESULTS: Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results (P for subgroup difference all > 0.05). CONCLUSION: Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis.
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Glicopéptidos , Hepatopatías , Humanos , Pronóstico , Supervivencia de Injerto , Hepatopatías/diagnósticoRESUMEN
A Gram-negative, aerobic, rod-shaped, motile bacterium with multi-flagella, strain RST, was isolated from bacterial wilt of tobacco in Yuxi city of Yunnan province, China. The strain contains the major fatty acids of C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The polar lipid profile of strain RST consists of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and unidentified aminophospholipid. Strain RST contains ubiquinones Q-7 and Q-8. 16S rRNA gene sequence (1,407 bp) analysis showed that strain RST is closely related to members of the genus Ralstonia and shares the highest sequence identities with R. pseudosolanacearum LMG 9673T (99.50%), R. syzygii subsp. indonesiensis LMG 27703T (99.50%), R. solanacearum LMG 2299T (99.28%), and R. syzygii subsp. celebesensis LMG 27706T (99.21%). The 16S rRNA gene sequence identities between strain RST and other members of the genus Ralstonia were below 98.00%. Genome sequencing yielded a genome size of 5.61 Mbp and a G + C content of 67.1 mol%. The genomic comparison showed average nucleotide identity (ANIb) values between strain RST and R. pseudosolanacearum LMG 9673T, R. solanacearum LMG 2299T, and R. syzygii subsp. indonesiensis UQRS 627T of 95.23, 89.43, and 91.41%, respectively, and the corresponding digital DNA-DNA hybridization (dDDH) values (yielded by formula 2) were 66.20, 44.80, and 47.50%, respectively. In addition, strains belonging to R. solanacearum phylotype I shared both ANIb and dDDH with strain RST above the species cut-off values of 96 and 70%, respectively. The ANIb and dDDH values between the genome sequences from 12 strains of R. solanacearum phylotype III (Current R. pseudosolanacearum) and those of strain RST were below the species cut-off values. Based on these data, we concluded that strains of phylotype I, including RST, represent a novel species of the genus Ralstonia, for which the name Ralstonia nicotianae sp. nov. is proposed. The type strain of Ralstonia nicotianae sp. nov. is RST (=GDMCC 1.3533T = JCM 35814T).
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A novel microfiber-like biohydrogel was fabricated by a facile approach relying on electroactive bacteria-induced graphene oxide reduction and confined self-assembly in a capillary tube. The microfiber-like biohydrogel (d = â¼1 mm) embedded high-density living cells and activated efficient electron exchange between cells and the conductive graphene network. Further, a miniature whole-cell electrochemical biosensing system was developed and applied for fumarate detection under -0.6 V (vs Ag/AgCl) applied potential. Taking advantage of its small size, high local cell density, and excellent electron exchange, this microfiber-like biohydrogel-based sensing system reached a linear calibration curve (R2 = 0.999) ranging from 1 nM to 10 mM. The limit of detection obtained was 0.60 nM, which was over 1300 times lower than a traditional biosensor for fumarate detection in 0.2 µL microdroplets. This work opened a new dimension for miniature whole-cell electrochemical sensing system design, which provided the possibility for bioelectrochemical detection in small volumes or three-dimensional local detection at high spatial resolutions.
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Técnicas Biosensibles , Grafito , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Bacterias , Fumaratos , Conductividad Eléctrica , Límite de DetecciónRESUMEN
BACKGROUND: Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins is useful for gastric cancer treatment and prognosis. Different IHC staining patterns reflect the complex biological phenomena underlying MMR deficiency. We herein report a rare IHC staining pattern of four MMR-related proteins in gastric cancer. CASE SUMMARY: A "null" IHC staining pattern of four MMR-related proteins, including MLH1, PMS2, MSH2, and MSH6, in a 67-year-old male patient with gastric cancer pT3N3aM0 revealed promoter hypermethylation of MLH1. Next-generation sequencing showed that these four genes exhibited changes. One of these was the somatic mutation of the missing copy number in exon 14 of MSH2. Mutation analysis using peripheral blood showed no germline mutations in these four genes. The patient had no history of personal or family tumor history. We classified this case as sporadic. The patient returned to normal after operation, and there were no signs of tumor metastasis and recurrence. After six cycles of adjuvant chemotherapy, the patient was discharged in a stable condition. The patient had a mild reaction to chemotherapy and a good prognosis. At present, 16 mo after the operation, the patient's condition is stable. CONCLUSION: Abnormal MMR protein expression, helpful for individualized follow-up care, helped identify a sporadic case lacking familial clinical management implications.
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PURPOSE: Our meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation ß blockers for hypertensive patients. METHODS: We searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs). FINDINGS: Eight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation ß blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation ß blockers. CONCLUSIONS: No significant difference was demonstrated between nebivolol and other second-generation ß blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation ß blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation ß blockers.
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Antihipertensivos , Hipertensión , Antihipertensivos/efectos adversos , Presión Sanguínea , Humanos , Hipertensión/tratamiento farmacológico , Nebivolol/farmacología , Nebivolol/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. METHODS: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). RESULTS: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. CONCLUSION: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH.
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Diabetes Mellitus Tipo 1/genética , Hemocromatosis/congénito , Hepcidinas/genética , Islotes Pancreáticos/inmunología , Adulto , Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/terapia , Femenino , Hemocromatosis/genética , Hemocromatosis/inmunología , Hemocromatosis/patología , Hemocromatosis/terapia , Heterocigoto , Humanos , Masculino , Mutación , LinajeRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Many plant viruses with monopartite or bipartite genomes have been developed as efficient expression vectors of foreign recombinant proteins. Nonetheless, due to lack of multiple insertion sites in these plant viruses, it is still a big challenge to simultaneously express multiple foreign proteins in single cells. The genome of Beet necrotic yellow vein virus (BNYVV) offers an attractive system for expression of multiple foreign proteins owning to a multipartite genome composed of five positive-stranded RNAs. Here, we have established a BNYVV full-length infectious cDNA clone under the control of the Cauliflower mosaic virus 35S promoter. We further developed a set of BNYVV-based vectors that permit efficient expression of four recombinant proteins, including some large proteins with lengths up to 880 amino acids in the model plant Nicotiana benthamiana and native host sugar beet plants. These vectors can be used to investigate the subcellular co-localization of multiple proteins in leaf, root and stem tissues of systemically infected plants. Moreover, the BNYVV-based vectors were used to deliver NbPDS guide RNAs for genome editing in transgenic plants expressing Cas9, which induced a photobleached phenotype in systemically infected leaves. Collectively, the BNYVV-based vectors will facilitate genomic research and expression of multiple proteins, in sugar beet and related crop plants.
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Edición Génica , Vectores Genéticos , Virus de Plantas , Plantas Modificadas Genéticamente , ARN Guía de Kinetoplastida , Beta vulgaris/genética , Enfermedades de las Plantas , Regiones Promotoras Genéticas , Nicotiana/genéticaRESUMEN
In this study, we aimed to evaluate the clinical and pathological factors that associated with sonographic appearances of triple-negative (TN) invasive breast carcinoma. With the ethical approval, 560 patients who were pathologically confirmed as invasive breast carcinoma were reviewed for ultrasound, clinical, and pathological data. Logistic regression analysis was used to identify the typical sonographic features for TN invasive breast carcinomas. The effect of clinical and pathological factors on the sonographic features of TN invasive breast carcinoma was studied. There were 104 cases of TN invasive breast carcinoma. The independent sonographic features for the TN subgroup included regular shape (odds ratio, OR = 2.14, p = 0.007), no spiculated/angular margin (OR = 1.93, p = 0.035), posterior acoustic enhancement (OR = 2.14, p = 0.004), and no calcifications (OR = 2.10, p = 0.008). Higher pathological grade was significantly associated with regular tumor shape of TN breast cancer (p = 0.012). Higher Ki67 level was significantly associated with regular tumor shape (p = 0.023) and absence of angular/spiculated margin (p = 0.005). Higher human epidermal growth factor receptor 2 (HER2) score was significantly associated with the presence of calcifications (p = 0.033). We conclude that four sonographic features are associated with TN invasive breast carcinoma. Heterogeneity of sonographic features was associated with the pathological grade, Ki67 proliferation level and HER2 score of TN breast cancers.
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Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Ultrasonografía/métodos , Adulto , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Antígeno Ki-67/metabolismo , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Invasividad Neoplásica , Receptor ErbB-2/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: Although primary thyroid lymphoma (PTL) and anaplastic thyroid carcinoma (ATC) both account for a rare portion of the morbidity of all thyroid malignancies, the therapeutic methods and prognosis for these two diseases are different. The purpose of this study was to investigate the sonographic characteristics of PTL and ATC and to compare the sonographic findings of PTL and ATC. METHODS: The study included 42 patients with histopathologically proven PTL (n=27) and ATC (n=15). The Clinical characteristics and sonographic findings were retrospectively reviewed and compared between the two groups. RESULTS: The mean age of patients with ATC was not significantly different from that in patients with PTL (P=0.601). The female-to-male ratio of patients with ATC was significantly lower than that of patients with PTL (P=0.029). Both PTL and ATC commonly present as a relatively large, solid mass on sonography with compressive symptoms, in which hoarseness was seen more frequently in ATC group (66.7%) than in PTL group (14.8%) (P=0.001). There is no significant difference in thyroid size, nodular size, margin, shape, echo texture, echogenicity, cystic change, vascularity and local invasion on sonography between ATC and PTL groups. Echogenic strands, markedly hypoechoic and enhanced posterior echo were seen more frequently in PTL group (92.6%, 92.6%, and 85.2%, respectively) than those in ATC group (6.7%, 60.0%, and 33.3%, respectively) (P<0.05), and calcification was seen more frequently in ATC group (80.0%) than in PTL group (0%) (P<0.001). Three ultrasound patterns were observed for PTL including diffuse type (25.9%), nodular type (48.2%) and mixed type (25.9%), while all ATC cases presented with nodular type (100.0%). Associated Hashimoto's thyroiditis occurred more frequently in PTL group (59.3%) than in ATC group (20.0%) (P=0.023). CONCLUSIONS: Certain sonographic features as a markedly hypoechogenicity, the presence of an enhanced posterior echo and linear echogenic strands, lack of calcification and associated Hashimoto's thyroiditis were valuable for distinguishing PTL from ATC. In contrast, heterogeneous echogenicity, uncircumscribed margin, irregular shape, and vascular pattern were not specific features for differential diagnosis.
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Plant microRNAs (miRNAs) are a class of non-coding RNAs that play important roles in plant development, defense, and symptom development. Here, 547 known miRNAs representing 129 miRNA families, and 282 potential novel miRNAs were identified in Beta macrocarpa using small RNA deep sequencing. A phylogenetic analysis was performed, and 8 Beta lineage-specific miRNAs were identified. Through a differential expression analysis, miRNAs associated with Beet necrotic yellow vein virus (BNYVV) infection were identified and confirmed using a microarray analysis and stem-loop RT-qPCR. In total, 103 known miRNAs representing 38 miRNA families, and 45 potential novel miRNAs were differentially regulated, with at least a two-fold change, in BNYVV-infected plants compared with that of the mock-inoculated control. Targets of these differentially expressed miRNAs were also predicted by degradome sequencing. These differentially expressed miRNAs were involved in hormone biosynthesis and signal transduction pathways, and enhanced axillary bud development and plant defenses. This work is the first to describe miRNAs of the plant genus Beta and may offer a reference for miRNA research in other species in the genus. It provides valuable information on the pathogenicity mechanisms of BNYVV.
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Beta vulgaris/genética , Beta vulgaris/virología , MicroARNs/genética , Enfermedades de las Plantas/virología , Virus de Plantas/fisiología , Beta vulgaris/citología , Beta vulgaris/metabolismo , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Reguladores del Crecimiento de las Plantas/biosíntesis , Hojas de la Planta/virología , Análisis de Secuencia de ARN , Transducción de SeñalRESUMEN
The regulatory transcriptional factor PATZ1 is abnormally up-regulated in diabetic endothelial cells (ECs) where it acts as an anti-angiogenic factor via modulation of fatty acid-binding protein 4 (FABP4) signaling. The aim of the present work was to elucidate the upstream molecular events regulating PATZ1 expression in diabetic angiogenesis. The bioinformatics search for microRNAs (miRNAs) able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-24 since the multiple targets of miR-24, which have so far been identified in beta cells, cardiomyocytes and macrophages, are all involved in diabetic complications. miR-24 expression was significantly impaired in the ECs isolated from diabetic hearts. Functionally, endothelial migration was profoundly inhibited by miR-24 suppression in Ctrl ECs, whereas miR-24 overexpression by mimics treatment effectively restored the migration rate in diabetic ECs. Mechanistically, miR-24 directly targeted the 3'untranslated region (3'UTR) of PATZ1, and miR-24 accumulation potentiated endothelial migration by reducing the mRNA stability of PATZ1. Together, these results suggest a novel mechanism regulating endothelial PATZ1 expression based on the down-regulation of miR-24 expression caused by hyperglycemia. Interfering with PATZ1 expression via miRNAs or miRNA mimics could potentially represent a new way to target endothelial PATZ1-dependent signaling of vascular dysfunction in diabetes.
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Dominio BTB-POZ , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/patología , Células Endoteliales/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Represoras/metabolismo , Animales , Células Cultivadas , Angiopatías Diabéticas/prevención & control , Células Endoteliales/patología , Silenciador del Gen , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Skeletal muscle growth and development are highly orchestrated processes involving significant changes in gene expressions. Differences in the location-specific and breed-specific genes and pathways involved have important implications for meat productions and meat quality. Here, RNA-Seq was performed to identify differences in the muscle deposition between two muscle locations and two duck breeds for functional genomics studies. To achieve those goals, skeletal muscle samples were collected from the leg muscle (LM) and the pectoral muscle (PM) of two genetically different duck breeds, Heiwu duck (H) and Peking duck (P), at embryonic 15 days. Functional genomics studies were performed in two experiments: Experiment 1 directly compared the location-specific genes between PM and LM, and Experiment 2 compared the two breeds (H and P) at the same developmental stage (embryonic 15 days). Almost 13 million clean reads were generated using Illumina technology (Novogene, Beijing, China) on each library, and more than 70% of the reads mapped to the Peking duck (Anas platyrhynchos) genome. A total of 168 genes were differentially expressed between the two locations analyzed in Experiment 1, whereas only 8 genes were differentially expressed when comparing the same location between two breeds in Experiment 2. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) were used to functionally annotate DEGs (differentially expression genes). The DEGs identified in Experiment 1 were mainly involved in focal adhesion, the PI3K-Akt signaling pathway and ECM-receptor interaction pathways (corrected P-value<0.05). In Experiment 2, the DEGs were associated with only the ribosome signaling pathway (corrected P-value<0.05). In addition, quantitative real-time PCR was used to confirm 15 of the differentially expressed genes originally detected by RNA-Seq. A comparative transcript analysis of the leg and pectoral muscles of two duck breeds not only improves our understanding of the location-specific and breed-specific genes and pathways but also provides some candidate molecular targets for increasing muscle products and meat quality by genetic control.
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Patos/embriología , Patos/genética , Embrión no Mamífero/embriología , Perfilación de la Expresión Génica , Desarrollo de Músculos/genética , Animales , Cruzamiento , Embrión no Mamífero/metabolismo , Músculo Esquelético/embriología , Músculo Esquelético/metabolismo , Fenotipo , Especificidad de la EspecieRESUMEN
Incubation temperature has an immediate and long-term influence on the embryonic development in birds. DNA methylation as an important environment-induced mechanism could serve as a potential link between embryos' phenotypic variability and temperature variation, which reprogrammed by DNA (cytosine-5)-methyltransferases (DNMTS) and Methyl-CpG binding domain proteins (MBPS) 3&5 (MBD3&5). Five genes in DNMTS and MBPS gene families were selected as target genes, given their important role in epigenetic modification. In this study, we aimed to test whether raising incubation temperature from 37.8°C to 38.8°C between embryonic days (ED) 1-10, ED10-20 and ED20-27 have effect on DNA methylation and whether DNMTS, MBPS play roles in thermal epigenetic regulation of early development in duck. Real-time quantitative PCR analysis showed that increased incubation temperature by 1°C has remarkably dynamic effect on gene expression levels of DNMTS and MBPS. Slight changes in incubation temperature significantly increased mRNA levels of target genes in breast muscle tissue during ED1-10, especially for DNMT1, DNMT3A and MBD5. In addition, higher temperature significantly increased enzyme activities of DNMT1 in leg muscle during ED10-20, liver tissue during ED1-10, ED20-27 and DNMT3A in leg muscle and breast muscle tissue during ED10-20. These results suggest that incubation temperature has an extended effect on gene expression levels and enzyme activities of DNMTS and MBPS, which provides evidence that incubation temperature may influence DNA methylation in duck during early developmental stages. Our data indicated that DNMTS and MBPS may involved in thermal epigenetice regulation of embryos during the early development in duck. The potential links between embryonic temperature and epigenetic modification need further investigation.
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Metilación de ADN , Patos/genética , Epigénesis Genética , Óvulo/crecimiento & desarrollo , Animales , Patos/embriología , Patos/metabolismo , Óvulo/metabolismo , Distribución Aleatoria , TemperaturaRESUMEN
PURPOSE: The efficacy of on-treatment hepatitis B surface antigen (HBsAg) levels in guiding pegylated interferon (PEG-IFN) therapy for chronic hepatitis B (CHB) infections is still controversial. The aim of this study is to quantitatively evaluate the efficacy of on-treatment HBsAg levels as a response-guided therapy strategy to guide PEG-IFN-based therapies for CHB. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library (1997-2013) for clinical research involving HBsAg quantification, and the response to PEG-IFN-based therapy. Pooled effect of HBsAg levels on guiding PEG-IFN-based therapies for CHB was evaluated using fixed-effects or random-effects model. RESULTS: From 13 studies (n = 1493 patients), patients with optimal on-treatment HBsAg levels were found to have a greater chance of attaining a response (RR 5.17, 95 % CI 3.75-7.11, p < 0.00001), and the pooled total response rate was 54 % (95 % CI 44-63 %). At week 12, patients without optimal on-treatment HBsAg levels had hardly achieved a response (the early non-response rate: 99 %, 95 % CI 98-100 %). At 24 weeks, the response rate increased to 79 % in HBeAg-negative patients. CONCLUSION: This meta-analysis suggested that on-treatment HBsAg quantification is effective in guiding the therapy of PEG-IFN in CHB infections, especially in HBeAg-negative patients.
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Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Antivirales/uso terapéutico , Portadores de Fármacos , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Humanos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND/PURPOSE: Lamivudine has been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV) infection in patients undergoing chemotherapy. However, information on breast cancer patients in particular has been lacking. The purpose of this meta-analysis was to assess the overall efficacy of lamivudine prophylaxis compared to untreated patients with hepatitis B S-antigen (HBsAg) seropositive breast cancer who had undergone chemotherapy. METHODS: Studies that compared the efficacy of treatment with lamivudine prophylaxis versus no prophylaxis in HBsAg seropositive breast cancer patients were identified through Medline, Cochrane, and Embase databases. RESULTS: Six studies involving 499 patients were analyzed. The rates of HBV reactivation in patients with lamivudine prophylaxis were significantly lower than those with no prophylaxis (risk ratio [RR] = 0.23, 95% confidence interval [CI]: 0.13-0.39, p < 0.00001). Patients given lamivudine prophylaxis had significant reductions in the rates of hepatitis attributable to HBV compared with those not given treatment (RR = 0.20, 95% CI: 0.08-0.47, p = 0.002). The rates of moderate and severe hepatitis in patients with lamivudine prophylaxis were significantly lower compared with those patients who had not received prophylaxis (RR = 0.25, 95% CI: 0.10-0.62, p < 0.003; RR = 0.25, 95% CI: 0.10-0.59, p = 0.002). Patients given lamivudine prophylaxis had significantly fewer disruptions of chemotherapy (RR = 0.36, 95% CI: 0.21-0.64, p = 0.0004). There was no significant heterogeneity in the comparisons. CONCLUSION: Lamivudine prophylaxis in HBsAg seropositive breast cancer patients undergoing chemotherapy is effective in reducing HBV reactivation and HBV-associated morbidity and mortality.
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Antivirales/uso terapéutico , Neoplasias de la Mama/complicaciones , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/prevención & control , Lamivudine/uso terapéutico , Activación Viral/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/virología , Quimioterapia , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Resultado del TratamientoRESUMEN
OBJECTIVE: To study expression of regucalcin (RGN) and prohibitin (PHB) genes in cirrhotic rat liver and to investigate the related effects of compound glutathione inosine injection (CGII) intervention. METHODS: Forty male Wistar rats were randomly divided into a control group (n=12) and a model group (n=28).The model was established by injecting sterile porcine serum (0.5 mL) into the rat abdominal cavity, twice weekly for 8 consecutive weeks; the control group rats were treated with physiological saline injection (0.5 mL) into the abdominal cavity with the same frequency and time span. During the modeling period, four rats from the model group were randomly selected at different time points to examine changes in liver pathology. Upon pathology confirmation of liver cirrhosis, the porcine serum injection was terminated. The remaining 24 rats in the model group were randomly divided into a fibrosis group and a CGII treatment group.The CGII group received CGII (intramuscular injection of 0.018 mL 100g-1 body weight) once a day for 6 continuous weeks; the fibrosis rats were treated with the same dosage of physiological saline with the same frequency and time span.Liver tissue morphology was examined by both hematoxylin-eosin and Masson's staining. RGN and PHB expression at the mRNA and protein levels in liver tissues were detected by real time RT-PCR and immunohistochemical staining, respectively. RESULTS: Both the mRNA and protein expression levels of RGN and PHB were significantly lower in the liver tissues of the fibrosis group than in the control group.CGII intervention led to significant alleviation of the liver fibrosis severity; moreover, the mRNA and protein expression levels of RGN and PHB were significantly higher than those in the fibrosis group. CONCLUSION: Down-regulation of regucalcin and prohibitin gene expression might contribute to the pathogenesis of liver cirrhosis.
Asunto(s)
Proteínas de Unión al Calcio/genética , Expresión Génica , Glutatión/toxicidad , Péptidos y Proteínas de Señalización Intracelular/genética , Cirrosis Hepática/genética , Proteínas Represoras/genética , Animales , Hidrolasas de Éster Carboxílico , Regulación hacia Abajo , Inosina , Masculino , Prohibitinas , Ratas , Ratas WistarRESUMEN
In this study, we aimed to use duck breast muscle and leg muscle, the 2 main productive muscle organs, as a model to elucidate the molecular mechanism controlling how the 2 muscles have different deposition capabilities, and to analyze the mechanisms facilitating duck muscle development posthatching. Peking duck breast muscle and leg muscle were collected 3, 7, and 16 wk posthatching. The morphology of the myofibers was observed by paraffin sectioning the muscles. The expression of genes involved in protein metabolism [mammalian target of rapamycin (mTOR), RPS6-p70-protein kinase (S6K), forkhead box O1 (FoxO1), muscle RING finger 1 (MuRF1), and atrogin-1 (MAFbx)] was detected using real-time quantitative PCR and Western blot assays, and the results indicated that breast muscle had a stronger capacity for both protein synthesis and protein degradation compared with leg muscle. Satellite cell frequency declined during muscle development in both tissues, and the expression of Pax3/7, satellite cell marker genes, was not significantly different between breast muscle and leg muscle. No notable apoptosis was observed in either tissue. The results of this study suggest that protein metabolism signaling is the main reason promoting duck skeletal muscle mass gain.