RESUMO
Plant cells employ intricate defense mechanisms, including mRNA decay pathways, to counter viral infections. Among the RNA quality control (RQC) mechanisms, nonsense-mediated decay (NMD), no-go decay (NGD), and nonstop decay (NSD) pathways play critical roles in recognizing and cleaving aberrant mRNA molecules. Turnip crinkle virus (TCV) is a plant virus that triggers mRNA decay pathways, but it has also evolved strategies to evade this antiviral defense. In this study, we investigated the activation of mRNA decay during TCV infection and its impact on TCV RNA accumulation. We found that TCV infection induced the upregulation of essential mRNA decay factors, indicating their involvement in antiviral defense and the capsid protein (CP) of TCV, a well-characterized viral suppressor of RNA silencing (VSR), also compromised the mRNA decay-based antiviral defense by targeting AtXRN4. This interference with mRNA decay was supported by the observation that TCV CP stabilized a reporter transcript with a long 3' untranslated region (UTR). Moreover, TCV CP suppressed the decay of known NMD target transcripts, further emphasizing its ability to modulate host RNA control mechanisms. Importantly, TCV CP physically interacted with AtXRN4, providing insight into the mechanism of viral interference with mRNA decay. Overall, our findings reveal an alternative strategy employed by TCV, wherein the viral coat protein suppresses the mRNA decay pathway to facilitate viral infection.
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Arabidopsis , Carmovirus , Arabidopsis/genética , Interferência de RNA , Carmovirus/genética , Degradação do RNAm Mediada por Códon sem Sentido/genética , RNA , Antivirais , RNA Viral/genéticaRESUMO
Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.
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Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controle , Resultado do Tratamento , ChinaRESUMO
Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.
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Neuropeptídeos/farmacologia , Neurotransmissores/farmacologia , Percepção Olfatória/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Animais , Infusões Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeos/administração & dosagem , Neurotransmissores/administração & dosagem , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacologia , Pirazinas/administração & dosagem , Pirazinas/farmacologia , Receptores de Neuropeptídeos/antagonistas & inibidores , Receptores de Neuropeptídeos/metabolismoRESUMO
Genome-wide association studies (GWASs) have provided many insights into cancer genetics. However, the molecular mechanisms of many susceptibility SNPs defined by GWASs in cancer heritability and in promoting cancer risk remain elusive. New research strategies, including functional evaluations, are warranted to systematically explore truly causal genetic variants. In this study, we developed an integrative functional genomics methodology to identify cancer susceptibility SNPs in transcription factor-binding sites across the whole genome. Employing integration of functional genomic data from c-Myc cistromics, 1000 Genomes, and the TRANSFAC matrix, we successfully annotated 12 SNPs present in the c-Myc cistrome with properties consistent with modulating c-Myc binding affinity in hepatocellular carcinoma (HCC). After genotyping these 12 SNPs in 1,806 HBV-related HCC case subjects and 1,708 control subjects, we identified a HCC susceptibility SNP, rs157224G>T, in Chinese populations (T allele: odds ratio = 1.64, 95% confidence interval = 1.32-2.02; p = 5.2 × 10(-6)). This polymorphism leads to HCC predisposition through modifying c-Myc-mediated transcriptional regulation of EPB41, with the risk rs157224T allele showing significantly decreased gene expression. Based on cell proliferation, wound healing, and transwell assays as well as the mouse xenograft model, we identify EPB41 as a HCC susceptibility gene in vitro and in vivo. Consistent with this notion, we note that EPB41 expression is significantly decreased in HCC tissue specimens, especially in portal vein metastasis or intrahepatic metastasis, compared to normal tissues. Our results highlight the involvement of regulatory genetic variants in HCC and provide pathogenic insights of this malignancy via a genome-wide approach.
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Carcinoma Hepatocelular/genética , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Predisposição Genética para Doença , Genoma Humano/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Alelos , Animais , Povo Asiático/genética , Estudos de Casos e Controles , China/etnologia , Feminino , Genes myc/genética , Genômica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Veia Porta , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The rainbow trout is a cold-water fish cultured in China. Heat stress has a serious impact on the summer survival and the yield of rainbow trout. A better understanding of the regulatory response of rainbow trout to heat stress will help in determining the relationship between heat stress signaling pathways and adaption mechanisms and help contribute to breeding new high-temperature tolerant strains of rainbow trout. In this study, the 48-h median lethal temperature (48h-LT50) of rainbow trout was determined as 22.5°C. We developed control (16°C) and heat-treated (22.5°C) groups and extracted RNA from the head kidney tissues for high-throughput sequencing to study the microRNA (miRNA) expression profiles. Twelve up-regulated and five down-regulated miRNAs were identified between the control and heat-treated groups. A total of 22 target genes were predicted for 6 of the differentially expressed miRNAs, including 31 negative miRNA-mRNA interactions. Important regulatory pathways under heat stress are related to the metabolism and immune responses of the rainbow trout. Our findings provide preliminary data for investigating the high-temperature molecular mechanism of the rainbow trout and can help producers to reduce the economic losses caused by high temperature weather.
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Resposta ao Choque Térmico , Rim/metabolismo , MicroRNAs/genética , RNA Mensageiro/genética , Truta/metabolismo , Animais , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Truta/genéticaRESUMO
The long non-coding RNA (lncRNA) PCAT-1 resides in the chromosome 8q24 cancer-risk locus and acts as a vital oncogene during tumorigenesis and progression. However, how PCAT-1 is post-transcriptionally regulated, for example, by small ncRNAs, such as microRNAs (miRNAs) is largely unknown. Here, we report how miRNAs regulate PCAT-1 expression and also investigate the biological significance of this regulation in hepatocellular carcinoma (HCC). We found that miR-215, a P53-inducible miRNA, is a key regulator of PCAT-1 expression in HCC and identified an interaction between miR-215 and PCAT-1 in dual luciferase reporter gene assays. We also found that post-transcriptional silencing of PCAT-1 by miR-215 or PCAT-1 siRNAs significantly inhibited proliferation of HCC cells and, conversely, that inhibition of endogenous miR-215 up-regulated PCAT-1 expression and promoted cell viability. The tumor-suppressing role of miR-215 was further confirmed in an in vivo mouse HCC xenograft model. Of note, gene profiling assays suggested that the kinase CRK-like proto-oncogene, adaptor protein (CRKL), is a potential downstream target of the miR-215-PCAT-1 axis in HCC, and we demonstrated that CRKL silencing significantly suppresses cell proliferation. Taken together and considering the essential role of CRKL in cancer cells, we propose that the TP53-miR-215-PCAT-1-CRKL axis might represent an important regulatory pathway in HCC. In summary, our results highlight the involvement of several ncRNAs in HCC and thus provide critical insights into the molecular pathways operating in this malignancy.
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Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/biossíntese , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Regulação para Cima , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteínas Nucleares/genética , Proto-Oncogene Mas , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. METHODS: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model. The mRNA and protein levels of Interleukin (IL)-6 were detected by qPCR and ELISA respectively. The signaling pathway-related proteins were investigated by western blot and immunofluorescence assay. RESULTS: HBcAg increased the expression and secretion of IL-6 through activating extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB). These activations can be blocked by specific inhibitors of the three pathways. CONCLUSIONS: HBcAg actives p38, ERK1/2 and NF-κB to enhance the production of IL-6 in hepatocytes. This provides a molecular mechanism to explain the association of cytoplasmic HBcAg with severe liver injury and inflammation.
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Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Interleucina-6/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Interleucina-6/análise , Interleucina-6/genética , Microscopia de Fluorescência , RNA Mensageiro/metabolismo , Transdução de SinaisRESUMO
As a well-known oncogene, B cell lymphoma-2 (BCL-2) can promote cancer cell survival through preventing their apoptosis. Several functional BCL-2 single nucleotide polymorphisms (SNPs), such as rs2279115, rs1801018, and rs1564483, have been identified and might contribute to cancer susceptibility. However, the involvement of these SNPs in small cell lung cancer (SCLC) was still unclear. As a result, we investigated associations between these three genetic variants and SCLC risk in a case-control design. Genotypes were determined in two independent case-control sets consisted of 520 SCLC patients and 1040 controls from two medical centers. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated utilizing unconditional logistic regression. We found that only BCL-2 rs2279115 genetic variant significantly contributed to decreased SCLC risk in Chinese Han populations, with the rs2279115 A allele as the protective allele. Stratified analyses of association between BCL2 rs2279115 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk of the limited stage SCLC but not the extensive stage disease. Our results indicate that the BCL-2 rs2279115 genetic variant was associated with SCLC risk in Chinese populations and support the hypothesis that SNPs in regulatory regions of oncogenes might contribute to cancer susceptibility.
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Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Following an in vitro bioactivity-guided fractionation procedure, 14 compounds including eight flavonoids and six phenylpropanoids were isolated and identified from the AcOEt fraction of Clinopodium chinense (Benth.) O. Kuntze. All constituents were tested for α-glucosidase and high glucose-induced injury in human umbilical vein endothelial cells (HUVECs) inhibitory activities. All constituents exhibited varying degrees α-glucosidase inhibitory activity and protective activity on HUVECs. Among them, luteolin (2), eriodictyol (5), ethyl rosmarinate (13), and clinopodic acids B (14) were proved to be potent α-glucosidase inhibitors with IC50 value ranging from 0.6 to 2.0 µm. Additionally, luteolin (2), naringenin (4), eriodictyol (5), ethyl (2R)-3-(3, 4-dihydroxyphenyl)-2-hydroxypropanate (9), caffeic acid (11), ethyl rosmarinate (13), and clinopodic acids B (14) significantly ameliorate HUVECs injury induced by high glucose with an approximate EC50 value of 3 - 36 µm. These results suggest that the 14 bioactive constituents were responsible for hypoglycemic and protective vascular endothelium effect of C. chinense (Benth.) O. Kuntze and their structure-activity relationship was also analyzed briefly. Eriodictyol, luteolin, ethyl rosmarinate, and clinopodic acids B were the potential lead compounds of antidiabetic drugs.
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Inibidores de Glicosídeo Hidrolases/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lamiaceae/química , Fenóis/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Glucose/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To study the clinical and imaging features of premature infants with different degrees of bronchopulmonary dysplasia (BPD). METHODS: A prospective study was performed on the clinical data of 59 premature infants (gestational age <32 weeks) with BPD. Among the 59 premature infants, 37 cases had mild BPD and the other 22 cases had moderate to severe BPD. The clinical and imaging data were compared between these premature infants with different degrees of BPD. RESULTS: The durations of mechanical ventilation, oxygen therapy, antibiotic therapy, parenteral nutrition, and hospitalization in the moderate to severe group were significantly longer than those in the mild group (P<0.05). The incidence of nosocomial infection and number of times of red blood cell transfusion in the moderate to severe group were significantly higher than that in the mild group. The rates of X-ray changes, including grade I respiratory distress syndrome (1 day after birth) and hypolucency of lungs (4-10 days and ≥ 28 days after birth) were significantly higher in the mild group than in the moderate to severe group. The rates of X-ray changes in classical BPD stage III (4-10 days after birth) and IV (≥ 28 days after birth) were significantly higher in the moderate to severe group than in the mild group. CONCLUSIONS: The durations of mechanical ventilation, oxygen therapy, and antibiotic therapy and the incidence of nosocomial infection are correlated with the severity of BPD. The premature infants with severer BPD need a longer duration of parenteral nutrition and more times of red blood cell transfusion and have more typical imaging changes of BPD. Imaging examination has a predictive value for the severity of BPD.
Assuntos
Displasia Broncopulmonar/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Iturin A is a potential lipopeptide antibiotic produced by Bacillus subtilis. Optimization of iturin A yield by adding various concentrations of asparagine (Asn), glutamic acid (Glu) and proline (Pro) during the fed-batch fermentation process was studied using an artificial neural network-genetic algorithm (ANN-GA) and uniform design (UD). Here, ANN-GA based on the UD data was used for the first time to analyze the fed-batch fermentation process. The ANN-GA and UD methodologies were compared based on their fitting ability, prediction and generalization capacity and sensitivity analysis. RESULTS: The ANN model based on the UD data performed well on minimal statistical designed experimental number and the optimum iturin A yield was 13364.5 ± 271.3 U/mL compared with a yield of 9929.0 ± 280.9 U/mL for the control (batch fermentation without adding the amino acids). The root-mean-square-error for the ANN model with the training set and test set was 4.84 and 273.58 respectively, which was more than two times better than that for the UD model (32.21 and 483.12). The correlation coefficient for the ANN model with training and test sets was 100% and 92.62%, respectively (compared with 99.86% and 78.58% for UD). The error% for ANN with the training and test sets was 0.093 and 2.19 respectively (compared with 0.26 and 4.15 for UD). The sensitivity analysis of both methods showed the comparable results. The predictive error of the optimal iturin A yield for ANN-GA and UD was 0.8% and 2.17%, respectively. CONCLUSIONS: The satisfactory fitting and predicting accuracy of ANN indicated that ANN worked well with the UD data. Through ANN-GA, the iturin A yield was significantly increased by 34.6%. The fitness, prediction, and generalization capacities of the ANN model were better than those of the UD model. Further, although UD could get the insight information between variables directly, ANN was also demonstrated to be efficient in the sensitivity analysis. The results of these comparisons indicated that ANN could be a better alternative way for fermentation optimization with limited number of experiments.
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Redes Neurais de Computação , Peptídeos Cíclicos/biossíntese , Algoritmos , Bacillus subtilis/crescimento & desenvolvimento , Bacillus subtilis/metabolismo , Técnicas de Cultura Celular por Lotes , Modelos TeóricosRESUMO
The aim of this study was to investigate the in vitro antioxidant activity of zinc ascorbate (AsA-Zn), its effects on the growth performance of and liver function in Magang geese under heat stress, and its potential mechanism. At AsA-Zn concentrations of 7.5, 15, 30, and 60 µmol/L, the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+) radical scavenging rate increased significantly by 120.85%, 53.43%, 36.12%, and 0.99%, respectively, compared with that of ascorbic acid (AsA), indicating that AsA-Zn had better antioxidant performance in vitro. In this study, Magang geese were divided into a control group (basal diet, CON) and experimental groups, who received the basal diet supplemented with 400 mg/kg AsA or 30 (AsA-Zn30), 60 (AsA-Zn60), or 90 (AsA-Zn90) mg/kg AsA-Zn. AsA-Zn supplementation considerably reduced the feed-to-gain ratio, whereas both AsA and AsA-Zn significantly increased the thymus index. Moreover, AsA-Zn supplementation improved serum protein levels, lipid metabolism, liver function, and antioxidant capacity while reducing hepatocyte vacuolar degeneration. Furthermore, supplementation with AsA-Zn60 significantly increased the total antioxidant capacity, glutathione peroxidase activity, and superoxide dismutase activity and decreased the malondialdehyde content in the serum, liver, and hepatic mitochondria (P < 0.05), with more pronounced effects in the AsA-Zn60 group. Moreover, supplementation with ASA-Zn regulated the Nrf 2 signaling pathway and significantly increased the expression of genes encoding antioxidant-related factors in the liver. In conclusion, AsA-Zn has good antioxidant activity, and AsA-Zn supplementation may improve the antioxidant capacity of heat-stressed geese and promote their growth. Supplementation with 30 mg/kg AsA-Zn is recommended.
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To fulfill the nutritional requirements of poultry, effective Zn supplementation is required due to Zn deficiency in basic feed. In this study, we investigated the effects of DMY-Zn (dihydromyricetin zinc chelate) on the growth performance, morphology, and biochemical indices; the expression of intestinal barrier-related genes; the intestinal microflora; and the cecum metabolome of Magang geese. A total of 300 14-day-old Magang geese (equal number of males and females) with an average body weight of 0.82 ± 0.08 kg were randomly divided into five groups and fed a basal diet; these groups were given DMY-Zn (low, medium, or high level of DMY-Zn with 30, 55, or 80 mg/kg Zn added to the basal diet) or ZnSO4 (80 mg/kg Zn added) for 4 weeks. Our results revealed that DMY-Zn significantly impacts growth and biochemical indices and plays a significant role in regulating the intestinal barrier and microflora. DMY-Zn is involved in the upregulation of intestinal barrier gene (ZO1 and MUC2) expression, as well as upregulated Zn-related gene expression (ZIP5). On the other hand, a low concentration of DMY-Zn increased the É diversity index and the abundance of Lactobacillus and Faecalibacterium. Additionally, a cecal metabolomics study showed that the main metabolic pathways affected by DMY-Zn were the pentose phosphate pathway, the biosynthesis of different alkaloids, and the metabolism of sphingolipids. In conclusion, DMY-Zn can reduce feed intake, increase the expression of intestinal barrier-related genes, help maintain the intestinal microflora balance, and increase the abundance of beneficial bacteria in the intestine to improve intestinal immunity.
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Prostate cancer (PCa) is one of the most common tumors affecting men all over the world. PCa has brought a huge health burden to men around the world, especially for elderly men, but its pathogenesis is unclear. In prostate cancer, epigenetic inheritance plays an important role in the development, progression, and metastasis of the disease. An important role in cancer invasion and metastasis is played by matrix metalloproteinases (MMPs), zinc-dependent proteases that break down extracellular matrix. We review two important forms of epigenetic modification and the role of matrix metalloproteinases in tumor regulation, both of which may be of significant value as novel biomarkers for early diagnosis and prognosis monitoring. The author considers that both mechanisms have promising therapeutic applications for therapeutic agent research in prostate cancer, but that efforts should be made to mitigate or eliminate the side effects of drug therapy in order to maximize quality of life of patients. The understanding of epigenetic modification, MMPs, and their inhibitors in the functional regulation of prostate cancer is gradually advancing, it will provide a new technical means for the prevention of prostate cancer, early diagnosis, androgen-independent prostate cancer treatment, and drug research.
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Epigênese Genética , Metaloproteinases da Matriz , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Metaloproteinases da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Inibidores de Metaloproteinases de Matriz/farmacologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genéticaRESUMO
Multiview clustering has received great attention and numerous subspace clustering algorithms for multiview data have been presented. However, most of these algorithms do not effectively handle high-dimensional data and fail to exploit consistency for the number of the connected components in similarity matrices for different views. In this article, we propose a novel consistency-induced multiview subspace clustering (CiMSC) to tackle these issues, which is mainly composed of structural consistency (SC) and sample assignment consistency (SAC). To be specific, SC aims to learn a similarity matrix for each single view wherein the number of connected components equals to the cluster number of the dataset. SAC aims to minimize the discrepancy for the number of connected components in similarity matrices from different views based on the SAC assumption, that is, different views should produce the same number of connected components in similarity matrices. CiMSC also formulates cluster indicator matrices for different views, and shared similarity matrices simultaneously in an optimization framework. Since each column of similarity matrix can be used as a new representation of the data point, CiMSC can learn an effective subspace representation for the high-dimensional data, which is encoded into the latent representation by reconstruction in a nonlinear manner. We employ an alternating optimization scheme to solve the optimization problem. Experiments validate the advantage of CiMSC over 12 state-of-the-art multiview clustering approaches, for example, the accuracy of CiMSC is 98.06% on the BBCSport dataset.
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Highly efficient single-component full-color emitting Ca6Y2Na2(PO4)6F2 (CYNPF):Eu2+,Tb3+,Mn2+ phosphors have been synthesized by a high-temperature solid-state reaction. Coupled with the Eu2+, Tb3+, and Mn2+ emission bands centered at 455 nm, 547 nm, and 580 nm, color-tunable white light can be generated. The energy transfer (ET) process from Eu2+ to Tb3+ and Mn2+ is attributed to the resonant dipole-dipole/dipole-dipole interaction mechanism with ultra-high ET efficiency (>90%). The emission color of the phosphors can be tuned from blue to yellowish green and orange with the corresponding CIE chromaticity coordinates of (0.1719, 0.1215), (0.2852, 0.4289), and (0.4752, 0.3903), respectively. Through controlling the concentration ratio of Tb3+ and Mn2+ ions, optimal white light emission can be obtained with CIE coordinates of (0.3381, 0.3353) excited at 365 nm, which is very close to the National Television Standards Committee white (0.330, 0.330). The thermal stability of the Eu2+, Tb3+, and Mn2+ codoped CYNPF phosphors has been investigated systematically. A single-component white LED (wLED) device has been fabricated by combining the CYNPF:Eu2+,Tb3+,Mn2+ phosphor with a 365 nm near-ultraviolet (n-UV) LED chip, which exhibits a high color rendering index (Ra = 80.2) along with a low color temperature of 5207 K and CIE coordinates of (0.3212, 0.3221). The results suggest that the phosphors can be used as a candidate material for single-component white phosphors for n-UV excited full-visible-spectrum wLEDs.
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OBJECTIVES: To address gaps in health services for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB), a treatment cascade model was used to evaluate patient retention and attrition at each successive step required to achieve a successful treatment outcome. METHODS: From 2015-2018, a four-step treatment cascade model was established in patients with confirmed MDR/RR-TB in southeast China. Step 1: diagnosis of MDR/RR-TB, step 2: Initiation of treatment, step 3: still under treatment at 6 month and step 4: cure or completion of MDR/RR-TB treatment, with each successive step including a gap that shows attrition of patients between steps. The retention and attrition of each step were graphed. Multi-variate logistic regression was carried out to further identify potential factors associated with the attrition. RESULTS: In the treatment cascade consisting of 1752 MDR/RR-TB patients, the overall patient attrition rate was 55.8% (978/1752), with 28.0% (491/1752), 19.9% (251/1261), and 23.4% (236/1010) of patients attrition in the first, second, and third gap. Factors associated with MDR/RR-TB patients not initiating treatment included age ≥60 years (OR:2.875), and time for diagnosis ≥30 days (OR: 2.653). Patients who were diagnosed with MDR/RR-TB through rapid molecular test (OR: 0.517) and non-migrant residents of Zhejiang Province (OR: 0.273) both exhibited a lower likelihood of attrition during the treatment initiation phase. Meanwhile, old age (OR: 2.190) and non-resident migrants to the province were factors associated with not completing ≥ 6 months of treatment. Old age (OR: 3.883), retreatment (OR: 1.440), and time to diagnosis ≥30 days (OR: 1.626) were factors contributing to poor treatment outcomes. CONCLUSION: Several programmatic gaps were identified in the MDR/RR-TB treatment cascade. Future policies should provide more comprehensive support for vulnerable populations to improve the care quality at each step.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Pessoa de Meia-Idade , Lactente , Rifampina/uso terapêutico , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Resultado do Tratamento , China/epidemiologia , Antituberculosos/uso terapêuticoRESUMO
Most plant viruses encode suppressors of RNA silencing (VSRs) to protect themselves from antiviral RNA silencing in host plants. The capsid protein (CP) of Turnip crinkle virus (TCV) is a well-characterized VSR, whereas SUPPRESSOR OF GENE SILENCING 3 (SGS3) is an important plant-encoded component of the RNA silencing pathways. Whether the VSR activity of TCV CP requires it to engage SGS3 in plant cells has yet to be investigated. Here, we report that TCV CP interacts with SGS3 of Arabidopsis in both yeast and plant cells. The interaction was identified with the yeast two-hybrid system, and corroborated with bimolecular fluorescence complementation and intracellular co-localization assays in Nicotiana benthamiana cells. While multiple partial TCV CP fragments could independently interact with SGS3, its hinge domain connecting the surface and protruding domains appears to be essential for this interaction. Conversely, SGS3 enlists its N-terminal domain and the XS rice gene X and SGS3 (XS) domain as the primary CP-interacting sites. Interestingly, SGS3 appears to stimulate TCV accumulation because viral RNA levels of a TCV mutant with low VSR activities decreased in the sgs3 knockout mutants, but increased in the SGS3-overexpressing transgenic plants. Transgenic Arabidopsis plants overexpressing TCV CP exhibited developmental abnormalities that resembled sgs3 knockout mutants and caused similar defects in the biogenesis of trans-acting small interfering RNAs. Our data suggest that TCV CP interacts with multiple RNA silencing pathway components that include SGS3, as well as previously reported DRB4 (dsRNA-binding protein 4) and AGO2 (ARGONAUTE protein 2), to achieve efficient suppression of RNA silencing-mediated antiviral defence.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Carmovirus , Viroses , Arabidopsis/metabolismo , Interferência de RNA , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Carmovirus/genética , Carmovirus/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Antivirais/metabolismo , RNA Viral/genética , Proteínas de Ligação a RNA/genéticaRESUMO
The rapid diagnosis of pathogenic infections plays a vital role in disease prevention, control, and public health safety. Recombinase-aided amplification (RAA) is an innovative isothermal nucleic acid amplification technology capable of fast DNA or RNA amplification at low temperatures. RAA offers advantages such as simplicity, speed, precision, energy efficiency, and convenient operation. This technology relies on four essential components: recombinase, single-stranded DNA-binding protein (SSB), DNA polymerase, and deoxyribonucleoside triphosphates, which collectively replace the laborious thermal cycling process of traditional polymerase chain reaction (PCR). In recent years, the CRISPR-Cas (clustered regularly interspaced short palindromic repeats-associated proteins) system, a groundbreaking genome engineering tool, has garnered widespread attention across biotechnology, agriculture, and medicine. Increasingly, researchers have integrated the recombinase polymerase amplification system (or RAA system) with CRISPR technology, enabling more convenient and intuitive determination of detection results. This integration has significantly expanded the application of RAA in pathogen detection. The step-by-step operation of these two systems has been successfully employed for molecular diagnosis of pathogenic microbes, while the single-tube one-step method holds promise for efficient pathogen detection. This paper provides a comprehensive review of RAA combined with CRISPR-Cas and its applications in pathogen detection, aiming to serve as a valuable reference for further research in related fields.
RESUMO
Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. The previous studies demonstrated that the endocannabinoid system played important roles in modulating several physiological functions such as sleep, olfaction, emotion, learning and memory, and reward behaviors. Mouse VD-hemopressin (α) [(m)VD-HPα], an 11-residue peptide derived from the α1 chain of hemoglobin, was recently presumed as a selective agonist of the CB1 receptor. The present study was undertaken to investigate the effects of (m)VD-HPα on the sleep-wake cycle and power spectrum of cortical EEG in freely moving rats and the potential neurons in the brain activated by (m)VD-HPα. The results showed that 20.1 nmol of (m)VD-HPα i.c.v. administration increased non-rapid eye movement (NREM) sleep in the first 2 h section accompanied by an increase in EEG delta (0.5-4 Hz) activity. The (m)VD-HPα-induced NREM sleep enhancement was due to extended episode duration instead of the episode number. In addition, the effect of (m)VD-HPα (20.1 nmol) on sleep-wake states was significantly attenuated by an antagonist of the CB1 receptor, AM251 (20 nmol, i.c.v.) but not by the CB2 receptor antagonist, AM630 (20 nmol, i.c.v.). In comparison with vehicle, (m)VD-HPα increased Fos-immunoreactive (-ir) neurons in the ventrolateral preoptic nucleus (VLPO), but reduced Fos-ir neurons in the lateral hypothalamus (LH), tuberomammillary nucleus (TMN), and locus coeruleus (LC). These findings suggest that (m)VD-HPα promotes NREM sleep via the CB1 cannabinoid receptor to probably activate VLPO GABAergic neurons, but inactivates the LH orexinergic, LC noradrenergic, and TMN histaminergic neurons.