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N6-methyladenosine (m6A) modification on viral RNAs has a profound impact on infectivity. m6A is also a highly pervasive modification for influenza viral RNAs. However, its role in virus mRNA splicing is largely unknown. Here, we identify the m6A reader protein YTHDC1 as a host factor that associates with influenza A virus NS1 protein and modulates viral mRNA splicing. YTHDC1 levels are enhanced by IAV infection. We demonstrate that YTHDC1 inhibits NS splicing by binding to an NS 3' splicing site and promotes IAV replication and pathogenicity in vitro and in vivo. Our results provide a mechanistic understanding of IAV-host interactions, a potential therapeutic target for blocking influenza virus infection, and a new avenue for the development of attenuated vaccines.
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Virus de la Influenza A , Gripe Humana , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/metabolismo , Gripe Humana/genética , Replicación Viral/genética , ARN Mensajero/genética , Factores de Empalme de ARN/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Accidente Cerebrovascular Isquémico , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Accidente Cerebrovascular Isquémico/inducido químicamente , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Óxidos de Nitrógeno , Óxido Nítrico , Puntuación de Riesgo Genético , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
IMPORTANCE: Type I interferon (IFN-I), produced by the innate immune system, plays an essential role in host antiviral responses. Proper regulation of IFN-I production is required for the host to balance immune responses and prevent superfluous inflammation. IFN regulatory factor 3 (IRF3) and subsequent sensors are activated by RNA virus infection to induce IFN-I production. Therefore, proper regulation of IRF3 serves as an important way to control innate immunity and viral replication. Here, we first identified Prohibitin1 (PHB1) as a negative regulator of host IFN-I innate immune responses. Mechanistically, PHB1 inhibited the nucleus import of IRF3 by impairing its binding with importin subunit alpha-1 and importin subunit alpha-5. Our study demonstrates the mechanism by which PHB1 facilitates the replication of multiple RNA viruses and provides insights into the negative regulation of host immune responses.
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Proteína 58 DEAD Box , Prohibitinas , Virus ARN , Receptores Inmunológicos , Transducción de Señal , Replicación Viral , Proteína 58 DEAD Box/antagonistas & inhibidores , Proteína 58 DEAD Box/metabolismo , Inmunidad Innata , Factor 3 Regulador del Interferón/metabolismo , Carioferinas/metabolismo , Prohibitinas/metabolismo , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/metabolismo , Interferón Tipo I/biosíntesis , Interferón Tipo I/inmunología , Virus ARN/crecimiento & desarrollo , Virus ARN/inmunología , Virus ARN/metabolismoRESUMEN
Hydrogen isotopic effect, as the key to revealing the origin of Earth's water, arises from the H/D mass difference and quantum dynamics at the transition state of reaction. The ion-molecule charge-exchange reaction between water (H2O/D2O) and argon ion (Ar+) proceeds spontaneously and promptly, where there is no transition-state or intermediate complex. In this energetically resonant process, we find an inverse kinetic isotope effect (KIE) leading to the higher charge transfer rate for D2O, by the velocity map imaging measurements of H2O+/D2O+ products. Using the average dipole orientation capture model, we estimate the orientation angles of C2v axis of H2O/D2O relative to the Ar+ approaching direction and attribute to the difference of stereodynamics. According to the long-distance Landau-Zener charge transfer model, this inverse KIE could be also attributed to the density-of-state difference of molecular bending motion between H2O+ and D2O+ around the resonant charge transfer.
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The reactive collision between He+ and CO2 plays an important role in substance evolutions of the planetary CO2-rich atmosphere. Using a three-dimensional ion velocity map imaging technique, we investigate the low-energy ion-molecule reactions He+ + CO2 â He + CO2+/He + CO+ + O/He + CO + O+. The velocity images of the products CO+ and O+ of dissociative charge-exchange reactions are distinctly different from those of charge-exchange product CO2+. The remarkable features of stereodynamics are observed in the dissociative charge-exchange reaction and are attributed to the spatial alignment of the initially random target CO2 during the He+ approach. Branching ratios of different channels of dissociative charge exchange are further obtained with the Doppler kinematics model, indicating a high preference for the energy-resonant channel.
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INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. Despite an overall downward trend in cancer mortality, HCC-related mortality continues to increase. KIFC3 is involved in cell division and cancers. However, the role of KIFC3 in HCC has yet to be elucidated. METHODS: A total of 36 cases of HCC tissues, 4 HCC cell lines, and TCGA databases were searched to explore the expression of KIFC3 in HCC. Subsequently, Western blot analysis, immunofluorescence, bioinformatic analysis, molecular docking, and Co-IP were performed to investigate the molecular mechanisms of KIFC3 in HCC. RESULT: We found that the expression of KIFC3 was upregulated in HCC, and high KIFC3 expression was related to poor overall survival. In addition, the knockdown of KIFC3 inhibited the proliferation, migration, and invasion of HCC cells in vitro, and impeded the growth of HCC in vivo, while overexpression of KIFC3 in HCC cells revealed the opposite effect. Mechanistically, KIFC3 promotes the progression of HCC through the PI3K/AKT/mTOR signalling. And KIFC3 had slight effect on the protein expression of p-PI3K, p-AKT and p-mTOR in TRIP13-ablated or LY294002-treated HCC cells. The KIFC3 knockdown could further enhance the inhibitory effect of LY294002. CONCLUSION: Our data revealed that KIFC3 is upregulated in HCC and may serve as a novel biomarker for predicting survival in HCC patients. Targeting KIFC3 may serve as a novel therapeutic strategy for HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cinesinas/genética , Cinesinas/metabolismoRESUMEN
Anionic carbonate CO3- has been found in interstellar space and the Martian atmosphere, but its production mechanism is in debate so far. To mimic the irradiation-induced reactions on icy micrograins in the Martian atmosphere and the icy shell of interstellar dust, here we report a laboratory investigation on the dissociative electron attachments to the molecular clusters of CO2. We find that anionic species (CO2)n-1O- and (CO2)n- (n = 2, 3, 4) are produced in the concerted reaction and further stabilized by the evaporative cooling after the electron attachment. We further propose a dynamics model to elucidate their competitive productions: the (CO2)n- yields survive substantially in the molecular evaporative cooling at the lower electron attachment energy, while the reactions leading to (CO2)n-1O- are favored at the higher attachment energy. This work provides new insights into physicochemical processes in CO2-rich atmospheres and interstellar space.
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INTRODUCTION: This study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE). METHODS: A total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs. RESULTS: The average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns. CONCLUSIONS: We applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.
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Derrame Pleural Maligno , Derrame Pleural , Humanos , Biomarcadores de Tumor , Inteligencia Artificial , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/patología , Derrame Pleural Maligno/diagnóstico por imagen , Sensibilidad y EspecificidadRESUMEN
Reaction dynamics in the liquid-vapor interface is one of the crucial physical sciences but is still starving for in-depth exploration. It is challenging to selectively detect the interfacial species or the yields of chemical reaction therein, meanwhile shielding or reducing the interference from the vapor and liquid bulk. Mass spectrometry is a straightforward method but is also frustrated in such a selective detection. Using a liquid microjet in combination with a pulsed electron beam, a linear time-of-flight mass spectrometer, and a quadrupole mass filter, we recently innovated time-delayed mass spectrometry for investigations of the liquid-vapor interface. In this Account, we illustrate how this unique method succeeds in disentangling different sources, i.e., the vapor and liquid-vapor interface, of the ionic yields of the electron impacts with a liquid beam of alcohol in vacuum. These achievements are basically attributed to the application of an onion-peeling strategy in the ion detection. Concretely, the microsecond time scale of molecular volatilization can be resolved well by tuning the delay time between the nanosecond pulses of incident electron bunch and ion attractor. First, the specific orientation of the interfacial molecule, i.e., a well-known fact about the hydrophobic hydrocarbon groups pointing outside the liquid surface of alcohol, is validated again. More importantly, the dynamic features of time-delayed mass spectra, in particular, for the ionic yields from the liquid-vapor interface, are rationalized explicitly. Moreover, we demonstrate evidence of in situ molecular dimers in the liquid-vapor interface of 1-propanol. As the first example of electron-induced reaction in the liquid-vapor interface, dimethyl ether can be synthesized in the liquid methanol interface due to local interfacial acidification by high-energy electron impacts. On the contrary, the low energy electron can lead to local basicity through dissociative electron attachment (DEA). Besides the primary low-energy electrons, the low-energy secondary and inelastically scattered electrons in the higher-energy impacts of the primary electrons can also participate in the DEA process. In contrast to the gas- or solid-phase DEAs, that in the liquid-vapor interface shows distinct differences in both the types and efficiencies of anionic products. With these and efforts in the future, we develop a molecular-level understanding of how the chemical reactions happen in the liquid-vapor interface.
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Electrones , Metanol , Iones , Metanol/química , Aniones , GasesRESUMEN
Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.
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COVID-19 , Enfermedades Transmisibles , Subtipo H1N1 del Virus de la Influenza A , Infección por el Virus Zika , Virus Zika , Humanos , PrevalenciaRESUMEN
BACKGROUND: We aimed to evaluate the correlation of apoprotein E (APOE) transcription and its methylation with immune microenvironment in HCC patients. MATERIAL AND METHODS: The expression profiles of APOE transcription, APOE methylation, and APOE protein were investigated via comprehensive bioinformatic analyses. After that, the association between the immune activation of HCC and APOE transcription and methylation were analyzed. Finally, the prognostic role and immune correlation of the APOE protein in 92 HCC individuals was determined. RESULTS: Based on data from TCGA, GEO, and ICGC datasets, the APOE mRNA was differentially expressed in HCC tissues compared with normal liver tissues. Further, APOE methylation was down-regulated in HCC tissues compared to normal liver tissues. APOE methylation was negatively correlated with APOE transcription in HCC (r=-0.52, p < 0.0001). Based on APOE methylation, the HCC patients were stratified into hypermethylation and hypomethylation subgroups as they exhibited different immune activation statuses. Further, HCC individuals with APOE hypermethylation had a closer immune correlation than those with hypomethylation. Notably, APOE transcription was associated with weak immune infiltrates and activation. Finally, over-expression of the APOE protein was correlated with better survival outcomes, but not correlated with PD-1 or CTLA4 protein in HCC revealed by immunohistochemistry. CONCLUSION: APOE methylation had a closer correlation with immune cells than APOE mRNA, indicating that APOE methylation might play an important role in immune regulation in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Apolipoproteínas E/genética , Apoproteínas/genética , Apoproteínas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Metilación de ADN , Neoplasias Hepáticas/patología , Pronóstico , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Microambiente TumoralRESUMEN
BACKGROUND: Liver failure is severe hepatic cellular damage caused by multiple factors that leads to clinical manifestations. Hepatic infiltration by malignancy is rarely reported as a cause of liver failure. CASE PRESENTATION: A 51-year-old male patient was admitted to the Wuhan Union Hospital complaining of bloating and jaundice. He had been diagnosed with polymyositis ten prior and was taking oral glucocorticoids. Physical examination revealed seroperitoneum and icteric sclera; laboratory tests revealed liver dysfunction, a coagulopathy, and negative results for the common causes of liver failure. Moreover, an ascitic tap and bone marrow aspirate and trephine confirmed a metastatic, poorly differentiated adenocarcinoma. These findings indicate that malignant infiltration is the most likely cause of liver failure. Regrettably, the patient refused complete liver and lymph node biopsies and was discharged on day 31. CONCLUSION: Clinicians should consider the possibility of malignant infiltration when approaching a case of liver failure with prodromal symptoms or imaging abnormalities, especially in patients with autoimmune diseases, such as polymyositis.
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Adenocarcinoma , Ictericia , Hepatopatías , Fallo Hepático , Neoplasias Primarias Desconocidas , Masculino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/diagnóstico , Fallo Hepático/diagnóstico , Fallo Hepático/etiología , Hepatopatías/etiología , Adenocarcinoma/complicacionesRESUMEN
PURPOSE: This study aimed to investigate the risk and prognostic factors of lymph node metastasis (LNM) in early-onset colorectal cancer (EO-CRC) and to develop nomograms for quantitatively predicting LNM and the cancer-specific survival (CSS). METHODS: A total of 22,405 EO-CRC patients were included in this study using the SEER database from 2010 to 2017. Logistic and Cox regression were used to identify risk and the potential prognostic factors, respectively, for EO-CRC with LNM. Subsequently, nomograms regarding the risk of LNM in EO-CRC patients and its corresponding CSS were constructed based on these factors. The discriminative ability, calibration and clinical usefulness of the nomograms were assessed by the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA). RESULTS: T-stage and pathological grade were the most represented factors in the predicted LNM nomogram, while histological type and combined distant metastases were the most represented in the nomogram for CSS in EO-CRC patients with LNM (all P < 0.05). The nomogram constructed based on the prognostic factors screened by Cox regression had good performance with C-index of 0.807 and 0.802 for the training and validation cohorts, respectively. The calibration curve showed that the nomograms' predictions were in line with actual observations. Additionally, the ROC curves indicated good discrimination, and the DCA curves implied significant clinical utility of the nomograms. CONCLUSION: The nomograms we constructed have significant performance in predicting the incidence and prognosis of LNM in EO-CRC patients, which may help clinicians to make better treatment decision making.
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Neoplasias Colorrectales , Nomogramas , Humanos , Metástasis Linfática , Pronóstico , Factores de Riesgo , Programa de VERF , Estadificación de NeoplasiasRESUMEN
A resonant system consisting of an excess electron and a closed-shell atom or molecule, as a temporary negative ion, is usually in doublet-spin states that are analogous to bright states of photoexcitation of the neutral. However, anionic higher-spin states, noted as dark states, are scarcely accessed. Here, we report the dissociation dynamics of CO- in dark quartet resonant states that are formed by electron attachments to electronically excited CO (a3Π). Among the dissociations to O-(2P) + C(3P), O-(2P) + C(1D), and O-(2P) + C(1S), the latter two are spin-forbidden in the quartet-spin resonant states of CO-, while the first process is preferred in 4Σ- and 4Π states. The present finding sheds new light on anionic dark states.
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INTRODUCTION: Respiratory dysfunction in patients with Parkinson's disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. METHODS: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson's disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey's post hoc test. RESULTS: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF25-75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = -0.248, p = 0.046), disease duration (r = -0.276, p = 0.026), H&Y scale (r = -0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = -0.277, p = 0.025), disease duration (r = -0.291, p = 0.019), H&Y scale (r = -0.434, p = 0.0001). FEF25-75% was negatively correlated with disease duration (r = -0.247, p = 0.047), H&Y scale (r = -0.278, p = 0.025). CONCLUSION: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.
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Enfermedad de Parkinson , Calidad de Vida , Humanos , Enfermedad de Parkinson/complicaciones , Estudios Transversales , China , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: The accuracy of alpha-fetoprotein (AFP) as a diagnostic marker for hepatocellular carcinoma (HCC) is insufficient, and the application of abnormal prothrombin (PIVKA-II) in HCC is still controversial. METHODS: Serum AFP and PIVKA-II levels were analyzed in 145 cases of HCC, 57 of benign liver disease, 55 of cholangiocarcinoma and gallbladder carcinoma, 112 of other gastrointestinal tumors with liver metastasis, and 101 healthy controls. Receiver operating characteristic curve and area under the curve were used to evaluate the diagnostic value of AFP and PIVKA-II for HCC. The changes in serum AFP and PIVKA-II levels before and after treatment in 47 HCC patients who underwent surgery and 77 who received interventional treatment were used to evaluate treatment efficacy and prognosis in HCC. RESULTS: The concentrations of AFP and PIVKA-II in the HCC group were significantly higher than those in other groups (p < 0.01). The diagnostic value of PIVKA-II in HCC was better than that of AFP, and combined detection improved the diagnostic sensitivity and specificity. The levels of AFP and PIVKA-II after liver cancer surgery were significantly lower than those before surgery. Elevated levels of PIVKA-II before surgery predicted disease progression, and patients who remained positive for PIVKA-II after surgery had worse prognosis than those who became negative after surgery. CONCLUSIONS: Combined detection of AFP and PIVKA-II is superior to both tests alone. We found that higher serum level of PIVKA-II indicates more severe HCC, with worse prognosis, while the level of AFP had no correlation with the prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , alfa-Fetoproteínas , Protrombina , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Biomarcadores , Pronóstico , Biomarcadores de TumorRESUMEN
The role of exogenous adenosine 5'-triphosphate (ATP) in the regulation of antioxidant response in plants under heavy metal stress is unclear. Here, we investigated the effects of exogenous ATP application on plant growth, antioxidant response, and Cd accumulation in maize seedlings. Treatment with 0.1 mM CdCl2 moderately reduced dry weight, decreased chlorophyll content, impaired photosynthesis, and increased lipid peroxidation in maize seedlings compared with controls. However, toxicity due to Cd was alleviated after 10-200 µM ATP treatment. Subsequently, the activity of Cd-regulated antioxidant enzymes, antioxidant metabolite accumulation, and total antioxidant capacity were drastically enhanced after 50 µM ATP treatment. Similar patterns were observed in the ADP-treated group but not in the AMP-treated group under Cd stress. However, the ATP-induced elevation in antioxidant defense ability was decreased by the inhibition of NADPH oxidase (NOX). ATP-induced elevation in NOX activity and H2O2 production was partly reversed by the inhibition of NOX in maize seedlings under Cd stress. Furthermore, ATP promoted Cd accumulation in the roots and shoots of maize seedlings. However, the ATP-induced increase in Cd accumulation was partly abolished by the inhibition of NOX. To our knowledge, this is the first report on the role and mechanism of exogenous ATP in regulating plant growth, antioxidant response, and heavy metal phytoextraction. The study provides a new method based on exogenous ATP for enhancing heavy metal tolerance in plants.
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Antioxidantes , Metales Pesados , Antioxidantes/metabolismo , Plantones , Cadmio/metabolismo , Zea mays/metabolismo , Peróxido de Hidrógeno/metabolismo , Metales Pesados/metabolismo , Estrés OxidativoRESUMEN
Classified as a class B infectious disease by the World Organization for Animal Health (OIE), bovine viral diarrhea/mucosal disease is an acute, highly contagious disease caused by the bovine viral diarrhea virus (BVDV). Sporadic endemics of BVDV often lead to huge economic losses to the dairy and beef industries. To shed light on the prevention and control of BVDV, we developed two novel subunit vaccines by expressing bovine viral diarrhea virus E2 fusion recombinant proteins (E2Fc and E2Ft) through suspended HEK293 cells. We also evaluated the immune effects of the vaccines. The results showed that both subunit vaccines induced an intense mucosal immune response in calves. Mechanistically, E2Fc bonded to the Fc γ receptor (FcγRI) on antigen-presenting cells (APCs) and promoted IgA secretion, leading to a stronger T-cell immune response (Th1 type). The neutralizing antibody titer stimulated by the mucosal-immunized E2Fc subunit vaccine reached 1:64, which was higher than that of the E2Ft subunit vaccine and that of the intramuscular inactivated vaccine. The two novel subunit vaccines for mucosal immunity developed in this study, E2Fc and E2Ft, can be further used as new strategies to control BVDV by enhancing cellular and humoral immunity.
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Virus de la Diarrea Viral Bovina Tipo 2 , Inmunidad Mucosa , Vacunas Virales , Animales , Bovinos , Humanos , Anticuerpos Antivirales , Diarrea , Células HEK293 , Vacunas de Subunidad/inmunología , Vacunas Virales/inmunología , Síndrome Hemorrágico de los Bovinos/prevención & controlRESUMEN
Antioxidant activities of five essential oils (cinnamon, thyme, clove, lavender and peppermint oils) and their major components (eugenol, thymol, linalool, and menthol) were evaluated on scavenging DPPH (2,2-diphenyl-1 picrylhydrazyl) free radicals, inhibiting polyunsaturated fatty acid oxidation in fish oil emulsion (FOE), and reducing oxidative stress in human red blood cells (RBC). The essential oils from cinnamon, thyme, clove and their main components, eugenol and thymol, exhibited the highest antioxidant activity in the FOE and RBC systems. It was found that the antioxidant activity of essential oils was positively correlated to the content of eugenol and thymol, while lavender and peppermint oils and their main components, linalool and menthol, had very low antioxidant activity. Compared with scavenging DPPH free radical activity, the antioxidant activity in FOE and RBC systems could better reflect the actual antioxidant potential of essential oil in preventing lipid oxidation and reducing oxidative stress in biological system.