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BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.
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BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.
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BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.
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Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Hepatectomía , Fallo Hepático , Neoplasias Hepáticas , Hígado , Nomogramas , Bazo , Humanos , Hepatectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Diagnóstico por Imagen de Elasticidad/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Estudios Prospectivos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Hígado/diagnóstico por imagen , Hígado/cirugía , Hígado/patología , Bazo/diagnóstico por imagen , Bazo/patología , Bazo/cirugía , Fallo Hepático/etiología , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Medición de Riesgo/métodos , Valor Predictivo de las Pruebas , Tamaño de los Órganos , Adulto , Curva ROC , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Cirrosis Hepática/patología , Cirrosis Hepática/complicacionesRESUMEN
Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.
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Aedes , Receptores Acoplados a Proteínas G , Animales , Aedes/metabolismo , Aedes/genética , Femenino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Células CHO , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Cricetulus , Conducta Alimentaria/fisiología , Mosquitos VectoresRESUMEN
Pseudomonas plecoglossicida is one of most important pathogenic bacterial species in large yellow croaker and several other commercially valuable fish species. In our previous study, a GacS deficient mutant (ΔgacS) was constructed and its virulence showed substantially attenuated. In present study, the safety, immunogenicity and protective effect of the ΔgacS were evaluated in large yellow croaker as a live-attenuated vaccine candidate. It was shown that the ΔgacS strain exhibited good safety to large yellow croaker and there was no mortality or clinical symptoms observed in all fish that infected by ΔgacS strain with the doses range from 2×105ï½107 CFU per fish via intraperitoneal injection (IP) or immersion (IM), and almost all bacteria were cleaned up in the spleen of the fish at 14-day post infection. Specific antibodies could be detected at 7-day and 14-day post infection by direct agglutination method, and the valences of antibodies and bactericidal activities of the serum were significant increased with vaccination doses and vaccination time. Moreover, the expressions of some molecules and cytokines involved in specific immune responses were detected in the ΔgacS strain immunization group and control group. After challenged by the wild-type (WT) strain XSDHY-P, the relative percentage survival (RPS) showed highly correlated with the immunized dosage regardless of vaccination methods. It showed that the RPS of the IP groups were 39.47%, 57.89%, 71.05% with the immune dosage in a descending order, respectively, and the RPS of the IM groups were 26.31%, 36.84%, 76.31% with the immune dosage in a descending order, respectively. In summary, the ΔgacS strain exhibited safety and good protective effect to large yellow croaker and was a potential live vaccine candidate.
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OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0âcm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873-0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC.
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Microbial degradation is an important solution for antibiotic pollution in livestock and poultry farming wastes. This study reports the isolation and identification of the novel bacterial strain Serratia entomophila TC-1, which can degrade 87.8 % of 200 mg/L tetracycline (TC) at 35 °C, pH 6.0, and an inoculation amount of 1 % (v/v). Based on the intermediate products, a possible biological transformation pathway was proposed, including dehydration, oxidation ring opening, decarbonylation, and deamination. Using Escherichia coli and Bacillus subtilis as biological indicators, TC degraded metabolites have shown low toxicity. Whole-genome sequencing showed that the TC-1 strain contained tet (d) and tet (34), which resist TC through multiple mechanisms. In addition, upon TC exposure, TC-1 participated in catalytic and energy supply activities by regulating gene expression, thereby playing a role in TC detoxification. We found that TC-1 showed less interference with changes in the bacterial community in swine wastewater. Thus, TC-1 provided new insights into the mechanisms responsible for TC biodegradation and can be used for TC pollution treatment.
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Biodegradación Ambiental , Serratia , Tetraciclina , Serratia/metabolismo , Serratia/genética , Tetraciclina/metabolismo , Antibacterianos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Aguas Residuales/microbiología , Animales , Eliminación de Residuos Líquidos/métodosRESUMEN
Delta like non-canonical Notch ligand 1 (DLK1), as a member of epidermal growth factor-like family, plays a critical role in somatic growth, tissue development and possibly tissue renewal. Though previous studies had indicated that DLK1 contributed to adipogenesis and myogenesis, it's still controversial whether DLK1 affects angiogenesis and how it interacts with Notch signaling with numerous conflicting reports from different models. Based on our preliminary finding that DLK1 expression was up-regulated in mice ischemic gastrocnemius and in the border zone of infarcted myocardium, we administered either recombinant DLK1 (rDLK1) or PBS in C57BL/6 mice after establishment of hindlimb ischemia (HLI) and myocardial infarction (MI), respectively. Exogenous rDLK1 administration significantly improved both blood perfusion of mice ischemic hindlimbs and muscle motor function on the 3rd, 7th day after HLI, by promoting neovascularization. Similar effect on neovascularization was verified in mice on the 28th day after MI as well as improvement of cardiac failure. Correspondingly, the number of CD34+KDR+ cells, indicated as endothelial progenitor cells (EPCs), was significantly in mice ischemic gastrocnemius by rDLK1 administration, which was abrogated by DAPT as the specific inhibitor of Notch intracellular domain (NICD). Furthermore, bone marrow mononuclear cells were obtained from C57BL/6 mice and differentiated to EPCs ex vivo. Incubation with rDLK1 triggered Notch1 mRNA and NICD protein expressions in EPCs as exposed to hypoxia and serum deprivation, promoting EPCs proliferation, migration, anti-apoptosis and tube formation. Otherwise, rDLK1 incubation significantly decreased intracellular and mitochondrial reactive oxygen species, increased ATP content and mitochondrial membrane potential, downregulated short isoform of OPA-1 expression whereas upregulated mitofusin (-1, -2) expression in EPCs by Notch1 signaling, which were all abrogated by DAPT. In summary, the present study unveils the pro-angiogenesis and its mechanism of rDLK1 through activation of Notch1 signaling in endothelial progenitor cells.
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Background: The relationship between the intake of dietary fatty acids (FA) and bone mineral density (BMD) has been the subject of prior investigations. However, the outcomes of these studies remain contentious. The objective of this research is to examine the link between dietary FA consumption among adolescents and BMD. Methods: This study utilized high-quality data from the National Health and Nutrition Examination Survey database, spanning 2011 to 2018, to explore the association between dietary fatty acids and bone health indicators in adolescents, including BMD and bone mineral content (BMC). Analyses were performed using weighted multivariate linear regression models, incorporating detailed subgroup analysis. Results: The study included 3440 participants. Analysis demonstrated that intake of saturated fatty acids (SFA) was positively correlated with total BMD, left arm BMD, total BMC, and left arm BMC. Monounsaturated fatty acid (MUFA) intake was positively correlated with BMC across most body parts, though it showed no correlation with BMD. Intake of polyunsaturated fatty acids (PUFA) was significantly inversely correlated with both BMD and BMC in most body parts. Additionally, subgroup analysis indicated that variables such as sex, age, standing height, and race significantly influenced the correlation between FA intake and BMD. Conclusions: Our study indicates that dietary intake of SFA may benefit to BMD in adolescents, in contrast to PUFA and MUFA. Therefore, we recommend that adolescents maintain a balanced intake of SFA to promote optimal bone mass development while preserving metabolic health.
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Densidad Ósea , Ácidos Grasos , Encuestas Nutricionales , Humanos , Densidad Ósea/efectos de los fármacos , Adolescente , Femenino , Masculino , Niño , Ácidos Grasos/administración & dosificación , Adulto Joven , Grasas de la Dieta/administración & dosificación , Estudios TransversalesRESUMEN
Gully erosion is a serious global environmental problem associated with land degradation and ecosystem security. Examining the influencing factors of gullies and determining susceptibility hold significance in environmental sustainability. The study evaluates the spatial distribution, influencing factors, and susceptibility of gullies in the Sunshui River Basin in Sichuan Province, Southwest China. The frequency ratio method supported by satellite images and the gully inventory dataset (1614 gully head points) with different influencing factors were applied to assess the distribution and susceptibility of gullies. Additionally, gully head points were grouped into a training set (70%, 1130 points) and a test set (30%, 484 points). Spatial distribution results indicated that most gullies are located in the middle and upper part of the basin, characterized by moderate elevation (2100-3300 m), steep slopes (11.63-27.34°), abandoned farmland, and Cambisols soil, and fewer gullies are located in lower part characterized by lower elevation, gentle slopes, and low vegetation coverage. Land use and land cover influence on susceptibility is significantly greater than other factors with a prediction rate of 33.9, especially farmland abandonment, while the occurrence of gullies is also more often on southwest-orientated slopes. Gully susceptibility highlighted that the study area affected by the very low, low, moderate, high, and very high susceptibilities to these gullies covered an area of about 16%, 23%, 32%, 26%, and 3% of the total basin respectively, which indicates 61% of the study area is susceptible to gully erosion. Moderate to high susceptibility is situated in the upper and middle part, consistent with the spatial distribution of gullies in the basin, and very high susceptibility (3%) is distributed in both the lower and upper parts of the basin. These results have important implications for soil loss control, land planning, and integrated watershed management in the mountainous areas of Southwest China.
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Monitoreo del Ambiente , Tecnología de Sensores Remotos , Ríos , China , Monitoreo del Ambiente/métodos , Ríos/química , Animales , Ecosistema , Conservación de los Recursos Naturales , Erosión del SueloRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries. AIM OF THE STUDY: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging. MATERIALS AND METHODS: We applied doses of 10-20 µL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-ß-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging. RESULTS: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-ß-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling. CONCLUSIONS: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging.
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Asteraceae , Fibroblastos , Envejecimiento de la Piel , Rayos Ultravioleta , Animales , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Ratones , Asteraceae/química , Aceites de Plantas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/patología , Piel/metabolismo , Masculino , FN-kappa B/metabolismo , FemeninoRESUMEN
Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.
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Infecciones por Circoviridae , Circovirus , FN-kappa B , Polisacáridos , ARN Largo no Codificante , Transducción de Señal , Sophora , Animales , Ratones , Circovirus/inmunología , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Infecciones por Circoviridae/inmunología , Polisacáridos/farmacología , Porcinos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , MicroARNs/genética , MicroARNs/metabolismo , Tolerancia Inmunológica/efectos de los fármacosRESUMEN
Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.
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Cardiotoxicidad , Poliestirenos , Proteínas Serina-Treonina Quinasas , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Proteína p53 Supresora de Tumor , Regulación hacia Arriba , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Cardiotoxicidad/etiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Poliestirenos/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Nanopartículas/toxicidad , Miocardio/metabolismo , Miocardio/patologíaRESUMEN
Tryptophan, commonly regarded as buried within the interior cores of proteins to maintain secondary structures, is now being recognized for its significant contributions to protein functionality. However, investigating functional tryptophan-involved interactions across the proteome and manipulating these interactions in live cells are considerable challenges. In this In Focus article, we summarize emerging advances in the field, describing innovative chemistries that leverage distinctive biochemical properties of the indole moiety for targeting and functionally manipulating tryptophan interactions.
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Proteínas , Triptófano , Triptófano/metabolismo , Triptófano/química , Proteínas/metabolismo , Proteínas/química , Humanos , Indoles/química , Indoles/metabolismo , Unión ProteicaRESUMEN
Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%-38.7%), level III aggression was 29.5% (95%CI = 26.3%-32.6%), and level VI aggression was 7.0% (95%CI = 5.4%-8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, "Increased motor activity-energy" emerged as the central symptom, with the highest centrality expected influence, followed by "Emotional Instability" and "Disruptive/aggression behavior". Notably, "Emotional Instability" appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, "Speech rate and amount" exhibited the strongest positive correlation with testosterone levels, followed closely by "Disruptive/aggression behavior". The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, "Increased motor activity-energy" stood out as the most influential symptom, and "Speech rate and amount" acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.
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Agresión , Trastorno Bipolar , Testosterona , Humanos , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/sangre , Testosterona/sangre , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Comorbilidad , Manía , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.
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Antivirales , Dioscorea , Virus de la Hepatitis B , Polisacáridos , Proteínas Quinasas p38 Activadas por Mitógenos , Humanos , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Polisacáridos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Células Hep G2 , Antivirales/farmacología , Dioscorea/química , Sinergismo Farmacológico , Nucleósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/genética , Antígenos e de la Hepatitis B/metabolismo , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Guanina/análogos & derivados , Guanina/farmacologíaRESUMEN
OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.