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Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.
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Candida albicans , Proteínas Fúngicas , Humanos , Ratones , Animales , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida albicans/metabolismo , Péptidos/metabolismoRESUMEN
BACKGROUND: Differentiated thyroid cancer (DTC) often seriously impacts patients' lives. Radionuclide Iodine-131 (131I) is widely used in treating patients with DTC. However, most patients know little about radionuclide therapy, and the treatment needs to be performed in a special isolation ward, which can cause anxiety and depression. AIM: To explore anxiety and depression status and their influencing factors after 131I treatment in patients with DTC. METHODS: A questionnaire survey was conducted among postoperative patients with DTC who received 131I treatment at our hospital from June 2020 to December 2022. General patient data were collected using a self-administered demographic characteristics questionnaire. The self-rating depression scale and self-rating anxiety scale were used to determine whether patients were worried about their symptoms and the degree of anxiety and depression. The patients were cate-gorized into anxiety, non-anxiety, depression, and non-depression groups. Single-variable and multiple-variable analyses were used to determine the risk factors for anxiety and depression in patients with thyroid cancer after surgery. RESULTS: A total of 144 patients were included in this study. The baseline mean score of self-rating anxiety and depression scales were 50.06 ± 16.10 and 50.96 ± 16.55, respectively. Notably, 48.62% (70/144) had anxiety and 47.22% (68/144) of the patients had depression. Sex, age, education level, marital status, household income, underlying diseases, and medication compliance significantly differed among groups (P < 0.05). Furthermore, multivariate logistic regression analysis showed that education level, per capita monthly household income, and medication compliance level affected anxiety (P = 0.015, 0.001, and 0.001 respectively. Patient's sex, marital status, and underlying diseases affected depression (P = 0.007, 0.001, and 0.009, respectively). CONCLUSION: Nursing interventions aiming at reducing the risk of anxiety and depression should target unmarried female patients with low education level, low family income, underlying diseases, and poor adherence to medications.
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Tick-borne viruses (TBVs) have increasingly caused a global public health concern. This study collected Rhipicephalus ticks in Guangdong, southern China to identify RNA viruses. Meta-transcriptome analysis revealed the virome in Rhipicephalus ticks, resulting in the discovery of 10 viruses, including Lihan tick virus, Brown dog tick phlebovirus 1 and 2 in the family Phenuiviridae, Mivirus and Wuhan tick virus 2 in the family Chuviridae, Wuhan tick virus 1 in the family Rhabdoviridae, bovine hepacivirus in the family Flaviviridae, Guangdong tick quaranjavirus (GTQV) in the family Orthomyxoviridae, Guangdong tick orbivirus (GTOV) in the family Reoviridae, and Guangdong tick Manly virus (GTMV) of an unclassified family. Phylogenetic analysis showed that most of these TBVs were genetically related to the strains in countries outside China, and GTQV, GTOV, and GTMV may represent novel viral species. These findings provided evidence of the long-distance spread of these TBVs in Guangdong, southern China, suggesting the necessity and importance of TBV surveillance.
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Aterosclerosis , Benzodioxoles/farmacología , Endotelio Vascular , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Proteínas Recombinantes/inmunología , Vimentina/inmunología , Animales , Antiinflamatorios no Esteroideos/farmacología , Aterosclerosis/inmunología , Aterosclerosis/prevención & control , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Humanos , Inflamación/metabolismo , Inflamación/prevención & control , RatonesRESUMEN
The intrinsic reason determining digestion performance of 100-160⯰C preheated food waste after recovering floatable oil (FO-recovered FW) was investigated using two-dimensional correlated infrared spectroscopy, three-dimensional fluorescence spectroscopy and high-throughput 16S rRNA amplicon sequencing. The results indicated that thermal temperature significantly affected CH4 production of FO-recovered FW due to different structural alteration degree of starch, protein, cellulose and lipid components. Fragmentation of starch mainly occurred at 100⯰C. The hydrolytic and acidogenic rate of starch was promoted and accordingly induced rapid growth of carbohydrate-fermenting bacteria, which resulted in severe acidification. Protein hydrolysis and cellulose H-bonds cleavage occurring at 120-160⯰C accelerated the accessible sites interacting with microbial hydrolytic enzymes, and growth of Cloacimonetes and Syntrophomonas enhanced CH4 production. Non-degradable humic acid-like organics remarkably formed at 160⯰C caused a carbon loss and digestion inhibiting/deteriorating. Pretreatment at 120⯰C was feasible for promoted methane production based on energy assessment.
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Alimentos , Metano , Anaerobiosis , Reactores Biológicos , ARN Ribosómico 16S , TemperaturaRESUMEN
Background: Silent information regulator 2 homolog 1 (SIRT1) is an evolutionarily conserved enzymes with nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase activity. SIRT1 is involved in a large variety of cellular processes, such as genomic stability, energy metabolism, senescence, gene transcription, and oxidative stress. SIRT1 has long been recognized as both a tumor promoter and tumor suppressor. Its prognostic role in cancers remains controversial. Methods: A meta-analysis of 13,138 subjects in 63 articles from PubMed, EMBASE, and Cochrane Library was performed to evaluate survival and clinicopathological significance of SIRT1 expression in various cancers. Results: The pooled results of meta-analysis showed that elevated expression of SIRT1 implies a poor overall survival (OS) of cancer patients [Hazard Ratio (HR) = 1.566, 95% CI: 1.293-1.895, P < 0.0001], disease free survival (DFS) (HR = 1.631, 95% CI: 1.250-2.130, P = 0.0003), event free survival (EFS) (HR = 2.534, 95% CI: 1.602-4.009, P = 0.0001), and progress-free survival (PFS) (HR = 3.325 95% CI: 2.762-4.003, P < 0.0001). Elevated SIRT1 level was associated with tumor stage [Relative Risk (RR) = 1.299, 95% CI: 1.114-1.514, P = 0.0008], lymph node metastasis (RR = 1.172, 95% CI: 1.010-1.360, P = 0.0363), and distant metastasis (RR = 1.562, 95% CI: 1.022-2.387, P = 0.0392). Meta-regression and subgroup analysis revealed that ethnic background has influence on the role of SIRT1 expression in predicting survival and clinicopathological characteristics of cancers. Overexpression of SIRT1 predicted a worse OS and higher TNM stage and lymphatic metastasis in Asian population especially in China. Conclusion: Our data suggested that elevated expression of SIRT1 predicted a poor OS, DFS, EFS, PFS, but not for recurrence-free survival (RFS) and cancer-specific survival (CCS). SIRT1 overexpression was associated with higher tumor stage, lymph node metastasis, and distant metastasis. SIRT1-mediated molecular events and biological processes could be an underlying mechanism for metastasis and SIRT1 is a therapeutic target for inhibiting metastasis, leading to good prognosis.
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PURPOSE: To identify a lncRNA signature to predict survival of breast cancer (BRCA) patients. METHODS: A total of 1222 BRCA case and control datasets were downloaded from the TCGA database. The weighted gene co-expression network analysis of differentially expressed mRNAs was performed to generate the modules associated with BRCA overall survival status and further construct a hub on competing endogenous RNA (ceRNA) network. LncRNA signatures for predicting survival of BRCA patients were generated using univariate survival analyses and a multivariate Cox hazard model analysis and validated and characterized for prognostic performance measured using receiver operating characteristic (ROC) curves. RESULTS: A prognostic score model of eight lncRNAs signature was identified as Prognostic score = (0.121 × EXPAC007731.1) + (0.108 × EXPAL513123.1) + (0.105 × EXPC10orf126) + (0.065 × EXPWT1-AS) + (- 0.126 × EXPADAMTS9-AS1) + (- 0.130 × EXPSRGAP3-AS2) + (0.116 × EXPTLR8-AS1) + (0.060 × EXPHOTAIR) with median score 1.088. Higher scores predicted higher risk. The lncRNAs signature was an independent prognostic factor associated with overall survival. The area under the ROC curves (AUC) of the signature was 0.979, 0.844, 0.99 and 0.997 by logistic regression, support vector machine, decision tree and random forest models, respectively, and the AUCs in predicting 1- to 10-year survival were between 0.656 and 0.748 in the test dataset from TCGA database. CONCLUSIONS: The eight-lncRNA signature could serve as an independent biomarker for prediction of overall survival of BRCA. The lncRNA-miRNA-mRNA ceRNA network is a good tool to identify lncRNAs that is correlated with overall survival of BRCA.
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Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , ARN Largo no Codificante/genética , Anciano , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Interferencia de ARN , ARN Mensajero/genética , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addition, the regulative mechanism of SOX2-OT is explored. METHODS: PubMed, EMBASE, and Cochrane Library and The Cancer Genome Atlas (TCGA) database were comprehensively explored to recover pertinent studies. We conducted an extensive inquiry to verify the implication of SOX2-OT expression in cancer patients by conducting a meta-analysis of 13 selected studies. Thirty-two TCGA databases were used to analyze the connection between SOX2-OT expression and both the overall survival (OS) and clinicopathological characteristics of cancer patients using R and STATA 13.0. Trial sequential analysis (TSA) was adopted in order to compute the studies' power. RESULTS: Thirteen studies involving 1172 cancer patients and 32 TCGA cancer types involving 9676 cancer patients were eventually selected. Elevated SOX2-OT expression was significantly related to shorter OS (HR = 2.026, 95% CI: 1.691-2.428, P < 0.0001) and disease-free survival (DFS) (HR = 2.554, 95% CI: 1.261-5.174, P = 0.0092) in cancer patients. Meanwhile, TSA substantiated adequate power to demonstrate the relationship between SOX2-OT expression and OS. The cancer patients with elevated SOX2-OT expression were more likely to have advanced clinical stage (RR = 1.468, 95% CI: 1.106-1.949, P = 0.0079), earlier lymphatic metastasis (P = 0.0005), earlier distant metastasis (P < 0.0001), greater tumor size (P < 0.0001), and more extreme tumor invasion (P < 0.0001) compared to those with low SOX2-OT expression. Meta-regression and subgroup analysis revealed that follow-up time, sample type, and tumor type could significantly contribute to heterogeneity for survival outcomes. The follow-up time could significantly explain heterogeneity for tumor, node, metastasis (TNM) stage. Furthermore, up to 500 validated target genes were distinguished, and the gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the validated targets of SOX2-OT were substantially enriched in cell adhesion, mRNA binding, and mRNA surveillance pathways. CONCLUSIONS: Elevated expression of SOX2-OT predicted a poor OS and DFS. Overexpression of SOX2-OT was correlated with more advanced tumor stage, earlier lymphatic metastasis, earlier distant metastasis, larger tumor size, and deeper tumor invasion. SOX2-OT-mediated cell adhesion, mRNA binding, or mRNA surveillance could be intrinsic mechanisms for invasion and metastasis.
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BACKGROUND: Reduced folate carrier 1 (RFC1) gene is a candidate for susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P). Association between RFC1 A80G polymorphism and NSCL/P have been studied. The published results are conflicting. METHODS: A meta-analysis of the association between RFC1 A80G polymorphism and NSCL/P was carried out using Stata13.0. A systematic literature search was performed through the PubMed, EMBASE, the Cochrane Library, Web of Science, ScienceDirect, EBSCOhost, China Biology Medicine databases, China National Knowledge Infrastructure and the Wanfang databases. All relevant studies up to 9 September 2019 were identified. RESULTS: Nine case-control studies including 4,229 total participants (1,334 NSCL/P children, 1,515 healthy children, 656 mothers of the NSCL/P children, and 724 mothers of healthy control children) were included in this study. The meta-analysis revealed that two genetic models of RFC1 A80G polymorphism in NSCL/P children increased risk of NSCL/P: the homozygote model (GG vs. AA, OR =2.346, 95% CI: 1.127-4.884) and the recessive model (GG vs. AG + AA, OR =1.503, 95% CI: 1.049-2.152). Further sensitivity analysis indicated that the frequency of G allele and GG genotype in NSCL/P children was significantly higher than those in the control. However, there was no significant statistical differences after Bonferroni correction. Subgroup analyses indicated the presence of the association of all the model with NSCL/P risk in the Indian children. RFC1 A80G polymorphism in the maternal population of NSCL/P children was not significantly associated with children NSCL/P. CONCLUSIONS: The RFC1 A80G polymorphism was a candidate for susceptibility to NSCL/P in the Indian pediatric population. More studies with larger samples are necessary to reach more conclusive outcomes.
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The interactions between Orange G (OG) with three kinds of ionic liquid surfactants (C10mimBF4, C12mimBF4, C16mimBF4) and CTAB were studied with UV-Vis spectra and conductivity measurements. The systematic changes in UV-Vis spectra with an increase of carbon-chain length may be observed in presence of OG. They correspond to CMC of every system, respectively, and the CMCs of four systems have exhibit the decrease of CMCs compared to pure surfactant. The binding constants are calculated from the results of conductivity measurements in the order of C16mimBF4>CTAB>C12mimBF4>C10mimBF4. Furthermore, system behaviors presented significant association of complex formation and micelles formation, i.e. the change in UV-Vis spectra before and after the formation of micelles in mixed systems. In addition, Fourier-transform infrared (FT-IR) spectroscopy and 1H NMR analysis further confirmed that the complexes are formed by hydrogen bond and van der Waal force. These findings could provide scientific guidance for extraction and separation of dyes.
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BDE-209 is the most commonly used commercial polybrominated diphenyl ether, and is of particular concern due to its accumulation and debromination to more toxic congeners in aquatic organisms. In this study, Japanese medaka were continuously exposed to BDE-209 with the exposure concentrations ranging from 1 to 1000 ng/L for 15, 30 and 60 days in a flowing-through exposure device. The results showed that BDE-209 could be accumulated in fish muscle at environmental relevant concentrations and its concentration in the muscle increased with the increase of exposure time and reached to a steady state. Toxicokinetic data showed that the dose-dependent half-life of BDE-209 in the muscle of medaka ranged from 16.5 to 19.4 days. Low brominated congeners could be detected, where tri- to hexa-BDEs were predominant congeners with up to 46% to 93% of total PBDEs and lower brominated BDEs may have slower elimination rates. Concentration level of BDE-155 ranged from several ng/g wet weight (ww) to a maximum of 178 ng/g ww. BDE-154 and BDE-153 as intermediates in fish under continuous exposure were negligible. By comparing with previous work, fish may have a different bioaccumulation capacity and metabolic pattern from other species, either because of species difference or the manner of exposures.
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Éteres Difenilos Halogenados/metabolismo , Éteres Difenilos Halogenados/toxicidad , Oryzias/metabolismo , Animales , Monitoreo del Ambiente , Halogenación , Músculos/efectos de los fármacos , Músculos/metabolismo , Bifenilos Polibrominados/metabolismo , Bifenilos Polibrominados/toxicidadRESUMEN
Accumulation of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in different phases in water was assessed in a wetland in Guanting, Beijing, China, by analyzing their concentrations in sediment, 30 d-exposed caged Chinese rare minnow (Gobiocypris rarus) and triolein embedded cellulose acetate membrane (TECAM). The applicability of TECAM to bioavailability assessment of PAHs and OCPs for aquatic organisms was also examined. The results showed that there were great differences of both bio-sediment accumulation factors (BSAFs) and TECAM-sediment accumulation factors (TSAFs) for target analytes between experiment sites with variation coefficients of 10%-70% and 20%-50%, respectively. The BSAFs and TSAFs were independent of relevant Kow. For the target pollutants especially PAHs, BSAFs for rare minnow were lower about one order of magnitude than those (1-4) predicted by equilibrium partitioning theory (EPT). However, TSAFs of PAHs and OCPs for TECAM were almost consistent with the EPT. Meanwhile, good correlations were found between the BSAFs and TSAFs for OCPs at 5 experiment sites (r = 0.80, 0.87, 0.83, 0.85 and 0.84, p < 0.01), but not good for PAHs (p > 0.1). It can be concluded that it is more reliable and accurate to assess the pollution status jointly using sediment, fish and TECAM, and that TECAM can be used as a biomimetic sampler to predict bioaccumulation potential of poorly biodegradable organic compounds like OCPs in fish.
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Peces/metabolismo , Hidrocarburos Clorados/metabolismo , Plaguicidas/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Animales , Disponibilidad Biológica , Materiales Biomiméticos , Monitoreo del Ambiente , Sedimentos Geológicos/química , Hidrocarburos Clorados/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Membranas Artificiales , Plaguicidas/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Chinese researchers have commenced a great deal of researches on the development of application fields of basic oxygen steel making furnace slag (BOF slag) for many years. Lots of new applications and properties have been found, but few of them in asphalt mixture of road construction engineering. This paper discussed the feasibility of BOF steel slag used as aggregate in asphalt pavement by two points of view including BOF steel slag's physical and micro-properties as well as steel slag asphalt materials and pavement performances. For the former part, this paper mainly concerned the mechanochemistry and physical changes of the steel slag and studied it by performing XRD, SEM, TG and mercury porosimeter analysis and testing method. In the second part, this paper intended to use BOF steel slag as raw material, and design steel slag SMA mixture. By using traditional rutting test, soak wheel track and modified Lottman test, the high temperature stability and water resistance ability were tested. Single axes compression test and indirect tensile test were performed to evaluate the low temperature crack resistance performance and fatigue characteristic. Simultaneously, by observing steel slag SMA pavement which was paved successfully. A follow-up study to evaluate the performance of the experimental pavement confirmed that the experimental pavement was comparable with conventional asphalt pavement, even superior to the later in some aspects. All of above test results and analysis had only one main purpose that this paper validated the opinion that using BOF slag in asphalt concrete is feasible. So this paper suggested that treated and tested steel slag should be used in a more extensive range, especially in asphalt mixture paving projects in such an abundant steel slag resource region.
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Hidrocarburos , Residuos Industriales , Metalurgia , Microscopía Electrónica de Rastreo , Minerales , Oxígeno , Porosidad , Silicatos , Estrés Mecánico , Propiedades de Superficie , TemperaturaRESUMEN
OBJECTIVE: To evaluate therapeutic effects suprapubic transvesical prostatectomy with opening the prostatic cavity wide on BPH with small volume. METHODS: From Aug 1994 to Dec 2003, fifty-six patients with BPH of small volume were treated by suprapubic trans vesical prostatectomy with opening the prostatic cavity wide. RESULTS: Forty-two patients have been followed up for 3 approximately 22 months. Neither incontinence nor bladder outlet obstruction had been observed. IPSS, QOL and PVR decreased from (31.0 +/- 2.3) score, (4.5 +/- 0.4) score and (230.0 +/- 30.0) ml (pre-operative) to (7.5 +/- 2.0) score, (1.5 +/- 0.5) score and disappearance (post-operative) respectively. All these differences were statistically significant (P <0.01). CONCLUSION: The procedure is effective for the patient with BPH of small volume.