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Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.
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Preterm delivery (PTD) is associated with severe adverse maternal and neonatal outcomes and higher medical costs. Therefore, PTD warrants more attention. However, predicting PTD remains a challenge for researchers. This study aimed to investigate potential prenatal predictors of PTD. We retrospectively recruited pregnant women who experienced either PTD or term delivery (TD) and underwent laboratory examinations at 32 weeks of gestation. We compared the test results between the two groups and performed logistic regression analysis and receiver operating characteristic (ROC) curve analysis to identify risk factors and predictive factors for PTD. Our investigation revealed that the PTD cohort exhibited statistically significant elevations in lymphocyte count, mean corpuscular hemoglobin concentration, calcium, uric acid, alkaline phosphatase, triglycerides, and total bile acids. Conversely, the PTD group demonstrated statistically significant reductions in mean corpuscular volume, homocysteine, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), neutrophils to (white blood cells-neutrophils) ratio (dNLR), and (neutrophils × monocytes) to lymphocyte ratio (SIRI). The ROC curve analysis revealed that calcium had an area under the curve (AUC) of 0.705, with a cut-off value of 2.215. Logistic regression analysis showed that premature rupture of membranes was an independent risk factor for PTD. Our study demonstrated that serum calcium levels, NLR, dNLR, and other laboratory tests conducted at 32 weeks of gestation can serve as predictors for PTD. Furthermore, we identified premature rupture of membranes as a risk factor for PTD.
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Calcio , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Calcio/sangre , Adulto , Nacimiento Prematuro/sangre , Edad Gestacional , Factores de Riesgo , Curva ROC , Biomarcadores/sangreRESUMEN
The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, with clinical outcomes ranging from asymptomatic infections to severe invasive diseases. The innate immune system, particularly macrophages, is of paramount importance in resisting the invasion of host tissues and organs by the trophozoites of E. histolytica. Parasite-derived pathogenic factors, such as lectins, play a pivotal role in the promotion of macrophage polarization phenotypes that have undergone alteration. Nevertheless, the precise mechanisms by which E. histolytica modulates immune polarization remain largely unknown. The current study focused on the immunomodulatory effects of the Igl-C fragment of E. histolytica Gal/GalNAc lectin on macrophage polarization. These results demonstrated that Igl-C could induce the secretion of IL-1ß, IL-6, and other cytokines, activating a mixed M1/M2 polarization state. M1 polarization of macrophages occurs in the early stages and gradually transitions to M2 polarization in the later stages, which may contribute to the persistence of the infection. Igl-C induces the macrophage M1 phenotype and causes the release of immune effector molecules, including iNOS and cytokines, by activating the NF-κB p65 and JAK-STAT1 transcription factor signaling pathways. Furthermore, Igl-C supports the macrophage M2 phenotype via JAK-STAT3 and IL-4-STAT6 pathways, which activate arginase expression in later stages, contributing to the tissue regeneration and persistence of the parasite. The involvement of distinct signaling pathways in mediating this response highlights the complex interplay between the parasite and the host immune system. These findings enhance our understanding of the Igl-C-mediated pathogenic mechanisms during E. histolytica infection.
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Entamoeba histolytica , Entamebiasis , Lectinas , Macrófagos , Entamoeba histolytica/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/parasitología , Entamebiasis/inmunología , Entamebiasis/parasitología , Animales , Ratones , Lectinas/metabolismo , Lectinas/inmunología , Citocinas/metabolismo , Activación de Macrófagos , Humanos , Transducción de Señal , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismoRESUMEN
The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.
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Glucósidos , Hipertensión Pulmonar , Subunidad alfa del Factor 1 Inducible por Hipoxia , Hipoxia , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Rehmannia , Serina-Treonina Quinasas TOR , Animales , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratones , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Rehmannia/química , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Glucósidos/farmacología , Hipoxia/tratamiento farmacológico , Hipoxia/fisiopatología , Hipoxia/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Apoptosis/efectos de los fármacosRESUMEN
The hard suckers commonly used in surgical operations often cause adsorption extrusion damage to the biological tissue. To tackle this problem, from the perspective of bionics, through in-depth observation and research on the special sucker adsorption process and adsorption mechanism of hypostomus plecostomus (HP), this paper proposes a bionic soft hypostomus plecostomus sucker (BSHPS) with a variable stiffness gradient structure with a good adsorption performance on soft moist irregular biological tissues. The BSHPS comprises a lip disc, a pre-valvular cavity, and a post-valvular cavity. Through the volume changes of the pre- and post-valvular cavities, a pressure difference is generated between the inside and outside of the sucker, enabling the lip disc to remain sealed. The experiments were carried out by an automatic tensile force measurement system equipped with a vacuum pump, and the results showed that in slippery environment, the adsorption performance of the BSHPS is improved by a maximum of 61.9% compared to that in dry environment. On a biological tissue surface, the adsorption force is as high as 13.7765 N. The most important advantage of the proposed BSHPS is that it can be firmly adsorbed the surface of soft moist irregular biological tissues, effectively slowing down or avoiding adsorption extrusion damage to the biological tissue. Therefore, the BSHPS is expected to have good application prospects in modern surgical medicine.
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Non-suicidal self-injury (NSSI) is an international public health problem. Qualitative synthesis of the psychological experiences associated with NSSI in adolescents remains limited. This study aimed to systematically review the factors, emotional experiences, coping strategies, and help-seeking experiences of adolescents who engage in NSSI. A comprehensive search of 10 databases was conducted. Two researchers independently conducted study screening, data extraction, and quality assessment. Eighteen articles were included and analyzed using a meta-aggregation approach. Four themes were identified: (1) factors contributing to NSSI, (2) emotions associated with engaging in NSSI, (3) coping strategies, and (4) potential barriers to seeking help. Our findings provide a comprehensive picture of the psychological experiences of adolescents who engage in NSSI. They primarily adopt negative coping strategies to deal with serious problems, and there are potential barriers to seeking help. Further research is needed to explore the true needs of adolescents, as well as how schools, families, and hospitals can play a collaborative role in improving adolescents' psychological issues.
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Adaptación Psicológica , Investigación Cualitativa , Conducta Autodestructiva , Humanos , Adolescente , Conducta Autodestructiva/psicología , Conducta del Adolescente/psicología , Aceptación de la Atención de Salud/psicología , Conducta de Búsqueda de Ayuda , EmocionesRESUMEN
The early monitoring and inactivation of bacteria are of crucial importance in preventing the further spread of foodborne pathogens. Staphylococcus aureus (S. aureus), a prototypical foodborne pathogen, is widely present in the natural environment and has the capability to trigger a range of diseases at low concentrations. In this work, we designed Fe3O4@SiO2-Au core-shell-satellite nanocomposites (NCs) modified with aptamer for efficient capture, high-sensitivity surface-enhanced Raman scattering (SERS) detection, and photothermal therapy (PTT) against S. aureus. Fe3O4@SiO2-Au NCs with tunable Au nanocrystal nanogaps were prepared. By combining the finite-difference time-domain (FDTD) method and experimental results, we studied the electric field distribution of Fe3O4@SiO2-Au under different Au nanogaps and ultimately obtained the optimal SERS substrate FSA-60. The modification of aptamer on the surfaces of FSA-60 could be used for the specific capture and selective detection of S. aureus, achieving a detection limit of as low as 50 cfu/mL. Furthermore, Apt-FSA-60 possessed excellent photothermal properties, demonstrating the strong photothermal killing ability against S. aureus. Therefore, Apt-FSA-60 is a promising high-sensitivity SERS substrate and efficient photothermal agent and is expected to be widely applied and promoted in future disease prevention and treatment.
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Aptámeros de Nucleótidos , Oro , Nanocompuestos , Dióxido de Silicio , Espectrometría Raman , Staphylococcus aureus , Staphylococcus aureus/efectos de los fármacos , Dióxido de Silicio/química , Nanocompuestos/química , Espectrometría Raman/métodos , Oro/química , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Terapia Fototérmica/métodosRESUMEN
BACKGROUND: Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are prevalent metabolic disorders with overlapping pathophysiological mechanisms. A comprehensive understanding of the shared molecular pathways involved in these conditions can advance the development of effective therapeutic interventions. METHODS: We used two datasets sourced from the Gene Expression Omnibus (GEO) database to identify common differentially expressed genes (DEGs) between T2D and NAFLD. Subsequently, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify the enriched biological processes and signaling pathways. In addition, we performed a protein-protein interaction (PPI) network analysis to identify hub genes with pivotal roles. To validate our findings, we established a type 2 diabetic mouse model with NAFLD. RESULTS: Our analysis identified 53 DEGs shared between T2D and NAFLD. Enrichment analysis revealed their involvement in signal transduction, transcriptional regulation, and cell proliferation as well as in the ferroptosis signaling pathways. PPI network analysis identified ten hub genes, namely CD44, CASP3, FYN, KLF4, HNRNPM, HNRNPU, FUBP1, RUNX1, NOTCH3, and ANXA2. We validated the differential expression of FYN, HNRNPU, and FUBP1 in liver tissues of a type 2 diabetic mouse model with NAFLD. CONCLUSIONS: Our study offers valuable insights into the shared molecular mechanisms underlying T2D and NAFLD. The identified hub genes and pathways present promising prospects as therapeutic targets to address these prevalent metabolic disorders.
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Biología Computacional , Diabetes Mellitus Tipo 2 , Modelos Animales de Enfermedad , Enfermedad del Hígado Graso no Alcohólico , Mapas de Interacción de Proteínas , Animales , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Ratones , Biología Computacional/métodos , Factor 4 Similar a Kruppel , Masculino , Ratones Endogámicos C57BL , Redes Reguladoras de Genes , Transducción de Señal , Perfilación de la Expresión Génica , HumanosRESUMEN
Generating antibodies specific to the functional epitope containing phosphotyrosine remains highly challenging. Here, we create an "epitope-directed immunogen" by incorporating fluorosulfate-l-tyrosine (FSY) with cross-linking activities into a specific tyrosine phosphorylation site of insulin receptor substrate 1 (IRS1) and immunizing mice to elicit site-specific antibody responses. By taking advantage of antibody clonal selection and evolution in vivo, we efficiently identified antibodies that target the IRS1 Y612 epitope and are capable of neutralizing the binding interactions between IRS1 and p85α mediated by the phosphorylation of Y612. This epitope-directed antibody elicitation by encoding the cross-linking reactivity in the immunogen potentially enables a general method for facile generation of neutralizing antibodies to protein tyrosine phosphorylation sites.
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BACKGROUND: Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). However, currently there are no tools specifically designed for predicting the occurrence of SIC in septic patients earlier. This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients. METHODS: Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to externally validate the nomogram. Univariate logistic regression analysis of the development cohort was performed firstly, and then multivariate logistic regression analysis was performed using backward stepwise method to determine the best-fitting model and obtain the nomogram from it. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram. RESULTS: A total of 548 and 245 patients, 55.1 and 49.4% with SIC occurrence, were included in the development and validation cohorts, respectively. Predictors contained in the prediction nomogram included shock, platelets, and international normalized ratio (INR). Patients with shock (odds ratio [OR]: 4.499; 95% confidence interval [CI]: 2.730-7.414; p < 0.001), higher INR (OR: 349.384; 95% CI: 62.337-1958.221; p < 0.001), and lower platelet (OR: 0.985; 95% CI: 0.982-0.988; p < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.879 (95% CI: 0.850-0.908) and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872 (95% CI: 0.826-0.917) and good calibration. The decision curve analysis of the nomogram provided better net benefit than the alternate options (intervention or no intervention). CONCLUSION: By incorporating shock, platelets, and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients. However, external validation is still required for further generalizability improvement of this nomogram.
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The investigation into the impact of gravel on water infiltration process and hydraulic parameters in stony soil could offer a theoretical basis to enhance water availability in rocky mountain area. A one-dimensional vertical infiltration experiment was used in this study. Six groups of gravel content of 0% (CK), 10% (W1), 20% (W2), 30% (W3), 40% (W4) and 50% (W5) were established to explore the changes in the wetting front, cumulative infiltration volume and infiltration rate. Then the accuracy of four infiltration models in simulating soil water infiltration processes was evaluated. Finally, Hydrus-1D was used to perform numerical inversion of the soil water content after infiltration. The findings revealed that: (1) When the infiltration time reached 300 min, the wetting front of the W1, W2, W3, W4 and W5 treatments was 11.00%, 17.00%, 32.25%, 38.75% and 54.50% lower than CK, the cumulative infiltration volume was 29.80%, 38.97%, 45.62%, 54.74% and 73.17% lower than CK, and the stable infiltration rate was 50.98%, 52.94%, 66.67%, 68.63% and 86.27% lower than CK. (2) The soil-water infiltration processes were accurately described by the Horton model, the coefficient of determination (R2) > 0.935. (3) The simulation results of Hydrus-1D showed that with the increase of gravel content, the values of the retention water content (θr), saturated water content (θs), shape coefficient (n) and saturated hydraulic conductivity (Ks) were decreased, the values of the reciprocal of air-entry (α) were increased. The value of R2 was more than 0.894, the root mean square error (RMSE) and mean absolute error (MAE) were less than 2%, which demonstrated that the Hydrus-1D model exhibited superior capability in simulating the changes of water content in stony soil in rocky mountain area. The findings of this study demonstrated that gravel could decrease the water infiltration process and affect the water availability. It could provide data support for the water movement process of stony soil and rational utilization of limited water resources in mountainous area.
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To improve product quality and obtain suitable processing parameters for crab apple slices (CASs) produced by continuous microwave drying (CMD), the effects of processing parameters, including slice thickness, microwave power, air velocity, and conveyor belt speed, on the evaluation indexes in terms of temperature, moisture content, color (L*, a*, b*), hardness, brittleness, and total phenolic content of CASs were investigated via the response surface method. The results indicated that microwave power has the greatest effect on the evaluation indexes applied to the CASs under CMD, followed by air velocity, slice thickness, and conveyor belt speed. To produce the desired product quality, the appropriate parameters for CMD of CASs were optimized as 1.25 mm slice thickness, 14,630 W microwave power, 0.50 m·s-1 air velocity, and 0.33 m·min-1 conveyor belt speed. Following that, the moisture content under CMD was found to be 13.53%, the desired color, hardness 0.79 g, brittleness 12.97 (number of peaks), and the total phenolic content 5.48 mg·g-1. This research provides a theoretical framework for optimizing the processing parameters of CASs using the response surface method.
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In this study, the removal effect of a new MOF-on MOF adsorbent based on Cu-Co bimetallic organic frameworks on tetracycline antibiotics (TCs) in water system was studied. The adsorbent (Cu-MOF@Co-MOF) were synthesized by solvothermal and self-assembly method at different concentrations of Co2+/Cu2+. The characterization results of SEM, XRD, XPS, FTIR and BET indicated that the MOF-on MOF structure of Cu-MOF@Co-MOF exhibited the best recombination and physicochemical properties when the molar ratio of Co2+: Cu2+ is 5:1. In addition, the Cu-MOF@Co-MOF have a high specific surface area and bimetallic clusters, which can achieve multi-target synergistic adsorption of TCs. Based on above advantages, Cu-MOF@Co-MOF provided a strong affinity and could efficiently adsorb more than 80% of pollutants in just 5 to 15 min using only 10 mg of the adsorbent. The adsorption capacity of tetracycline and doxycycline was 434.78 and 476.19 mg/g, respectively, showing satisfactory adsorption performance. The fitting results of the experimental data were more consistent with the Langmuir isotherm model and pseudo-second-order kinetic model, indicating that the adsorption process of TC and DOX occurred at the homogeneous adsorption site and was mainly controlled by chemisorption. Thermodynamic experiments showed that Cu-MOF@Co-MOF was thermodynamically advantageous for the removal of TCs, and the whole process was spontaneous. The excellent adsorption capacity and rapid adsorption kinetics indicate the prepared MOF-on MOF adsorbent can adsorb TCs economically and quickly, and have satisfactory application prospects for removing TCs in practical environments. The results of the study pave a new way for preparing novel MOFs-based water treatment materials with great potential for efficient removal.
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Antibacterianos , Cobre , Estructuras Metalorgánicas , Tetraciclina , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Cobre/química , Estructuras Metalorgánicas/química , Antibacterianos/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Tetraciclina/química , Tetraciclina/aislamiento & purificación , Purificación del Agua/métodos , Cobalto/química , CinéticaRESUMEN
The coarctation of the aorta (CoA) combined with heart defects or cerebral artery aneurysms is more prevalent in clinical practice. However, cases of concurrent bilateral iliac artery dissection (IAD) are extremely rare and have not been reported. Here, we described a case with CoA combined with bilateral IAD. The patient, a 62-year-old male, presented with acute intermittent claudication accompanied by pain and aching in both lower limbs after walking. Following a thorough medical history inquiry and examination, the patient was diagnosed with acute bilateral IAD combined with CoA. The patient underwent endovascular treatment. Postoperatively, the aortic diameter recovered, and the bilateral IAD disappeared, yielding satisfactory therapeutic results. Conclusively, endovascular treatment of aortic coarctation combined with IAD is an effective therapeutic approach, enhancing patient survival and improving their quality of life.
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Coartación Aórtica , Disección Aórtica , Procedimientos Endovasculares , Humanos , Masculino , Persona de Mediana Edad , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Procedimientos Endovasculares/métodos , Coartación Aórtica/complicaciones , Coartación Aórtica/cirugía , Coartación Aórtica/diagnóstico , Arteria Ilíaca , Aneurisma Ilíaco/complicaciones , Aneurisma Ilíaco/cirugía , Aneurisma Ilíaco/diagnóstico , Claudicación Intermitente/etiología , Claudicación Intermitente/diagnóstico , Resultado del Tratamiento , Calidad de VidaRESUMEN
OBJECTIVE: Head and Neck Squamous Cell Carcinoma (HNSCC) ranks as the sixth most prevalent form of cancer worldwide. MRE11 protein contains multiple domains that play a role in the initiation of DNA repair. This study aimed to elucidate the expression and prognostic significance of MRE11 in HNSCC. MATERIAL AND METHODS: The Cancer Genome Atlas (TCGA-HNSCC) dataset comprising 520 HNSCC tissues and 44 normal tissues was initially used to evaluate the association between MRE11 expression and clinicopathologic characteristics. Kaplan-Meier plot was utilized for survival analysis. MRE11-immune cell interaction was analyzed using Tumor Immune Estimation Resource (TIMER) database. Further, Insilco methods were used to explore the protein network and its association with other pathways. Quantitative reverse transcription PCR (RT-qPCR) was used to validate the MRE11 mRNA expression in oral squamous cell carcinoma (OSCC) tissues in patient samples. RESULTS: MRE11 expression was upregulated in HNSCC, and the expression significantly varied across different clinical stages, pathological grades, and initial treatment outcomes. Further, high MRE11 expression is associated with poorer survival outcomes. MRE11 overexpression is also linked to the activation of the HIPPO signaling pathway, the mTOR signaling pathway, and the MYC/MYCN signaling pathway. CONCLUSION: MRE 11 can be considered a novel prognostic biomarker for HNSCC, which can be leveraged for promising treatment outcomes. This research highlights MRE11 as a novel molecular biomarker for HNSCC and offers a new direction for its treatment, explicitly targeting MRE11 and its network for therapeutic intervention.
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Secondary nephrosis is a series of chronic kidney diseases secondary to other underlying diseases, mainly manifesting as structural and functional abnormalities of the kidneys and metabolic disorders. It is one of the important causes of end-stage renal disease, with high morbidity and significant harm. Iron is an essential metal element in human cells, and ferroptosis is a non-traditional form of iron-dependent cell death, and its main mechanisms include iron accumulation, lipid metabolism disorders, abnormal amino acid metabolism, and damage to the antioxidant system. Recently studies have found that ferroptosis is involved in the occurrence and progression of secondary nephrosis, and the mechanism of ferroptosis in different secondary nephrosis vary. Therefore, an in-depth and systematic understanding of the association between ferroptosis and secondary nephrosis, as well as their specific regulatory mechanisms, can provide a theoretical basis for the diagnosis, prevention, treatment, and prognosis assessment of secondary nephrosis, laying the foundation for exploring new clinical therapeutic targets for secondary nephrosis.
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Ferroptosis , Hierro , Nefrosis , Humanos , Ferroptosis/fisiología , Hierro/metabolismo , Nefrosis/metabolismo , Animales , Fallo Renal Crónico/complicaciones , Metabolismo de los LípidosRESUMEN
Three-dimensional (3D) network provide a promising platform for construction of high sensitive electrochemical immunosensor due to the benefits of high specific surface area and electron mobility. Herein, a sensitive label-free electrochemical immunosensor based on Au nanoparticles modified Ni-B nanosheets/graphene matrix was constructed to detect diethylstilbestrol (DES). The 3D network not only could increase the electron transport rate and surface area, but also could provide confinement area, which is conducive to increases the collision frequency with the active site. Moreover, Au NPs also have good biocompatibility, which is beneficial for ligating antibodies. Benefiting from the 3D network structure and Au collective effect, the electrochemical immunosensor possess sterling detection ability with wide linear response range (0.00038-150 ng/mL) and low detection limit (31.62 fg/mL). Moreover, the constructed immunosensor can also be extend to detect DES in Tap-water and river water. This work may provide a novel material model for the construction of high sensitive immunosensor.
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Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment released into the bloodstream during the death of lung epithelial cells, serving as a predictive biomarker in diagnosing non-small cell lung cancer (NSCLC) and need to be accurately detected. Herein, a dual-responsive label-free electrochemical immunosensor was developed based on a three-dimensional ordered interconnecting macroporous carbon skeleton material modified with gold-cobalt nanoparticles (Au/Co NPs-3D MCF) to detect cytokeratin-19 fragment (CYFRA21-1). The three-dimensional ordered interconnect macroporous structure, by providing a high specific surface area and an electrochemically active area, not only enhances the electron transport channel and reduces mass transfer resistance, but also offers a confined region that elevates the collision frequency with the active site. In addition to exhibiting excellent biocompatibility for antibody binding, gold-cobalt nanoparticles contribute significantly to the overall robustness of the immunosensor. By capitalizing on the 3D network structure and collective effect of Au and Co NPs, the Au/Co NPs-3D MCF immunosensors exhibit exceptional response signals in both chronocurrent testing and square-wave voltammetry, allowing for a wide linear response range of 0.0001-100â¯ng/mL and a low detection limit. Moreover, the constructed immunosensor is capable of detecting CYFRA21-1 in human serum and has the potential for further extension to detect multiple biomarkers. This work opens up new avenues for the construction of other highly selective 3D network immunosensors.
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To this date, COVID-19 remains an unresolved pandemic, and the impairment of redox homeostasis dictates the severity of clinical outcomes. Here we examined initial UCLA cohort of 440 COVID-19 patients hospitalized between March 1st and April 1st, 2020, representing the first wave of the pandemic. The mean age was 58.88 ± 21.12, among which males were significantly more than females (55.5 % vs. 44.5 %), most distinctively in age group of 50-69. The age groups of 50-69 (33.6 %) and ≥70 (34.8 %) dominated. The racial composition was in general agreement with Census data with slight under-representation of Hispanics and Asians, and over-representation of Caucasians. Smoking was a significant factor (28.8 % vs. 11.0 % in LA population), likewise for obesity (BMI ≥30) (37.4 % vs. 27.7 % in LA population). Patients suffering from obesity or BMI<18.5 checked into ICU at a significantly higher rate. A 74.5 % of the patients had comorbidities including diabetes, chronic kidney disease, chronic pulmonary disease, congestive heart failure and peripheral vascular disease. The levels of d-dimer were drastically upregulated (1159.5 ng/mL), indicating hypercoagulative state. Upregulated LDH (328 IU/L) indicated significant tissue damages. A distorted redox hemeostasis is a common trait associated with these risk factors and clinical markers. A quarter of the patients received antivirals, among which Remdesivir most prescribed (23.6 %). Majority received antithrombotics (75 %), and antibiotics. Upon admission, 67 patients were intubated or received CPR; 177 patients eventually received intensive care (40.2 %). While 290 were discharged alive, 10 remained hospitalized, 73 were transferred, and 36 died with 3 palliatively discharged. In summary, our data fully characterized a Californian cohort of COVID-19 at the breaking phase of the pandemic, indicating that population demographics, biophysical characters, comorbidities and molecular pathological parameters have significant impacts on the evolvement of a pandemic. These provide critical insights into effective management of COVID-19, and future break from another pathogen.
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Solanum lycopersicum L. can be classified into low Cd-accumulating and high Cd-accumulating types based on their accumulation characteristics of cadmium (Cd). There are many common S. lycopersicum varieties available in the market, but their specific Cd tolerance and enrichment abilities are not well understood. This article uses two S. lycopersicum cultivars, Yellow Cherry and Yellow Pearl, as experimental materials. The experimental method of soil pot planting was adopted, and Cd concentrations in the soil were added at 0, 0.6, 1.5, 2.5, 5, and 10 mg/kg. The changes in Cd content, biomass, photosynthetic pigment content, and photosynthetic parameters of the two S. lycopersicum cultivars were analyzed to screen for low-accumulation S. lycopersicum cultivars. The results showed that S. lycopersicum are Cd-sensitive plants. The Cd accumulation, photosynthetic parameters, and other basic indicators of Yellow Cherry basically showed significant differences when the soil Cd concentration was 0.6 mg/kg, and the biomass showed significant differences when the soil Cd concentration was 1.5 mg/kg. Except for the Cd accumulation in the roots and leaves of Yellow Pearl, which showed significant differences at a soil Cd concentration of 0.6 mg/kg, the other indicators basically showed significant differences when the soil Cd concentration was 1.5 mg/kg. When the soil Cd concentration was 0.6 mg/kg, the Cd accumulation in the fruit of Yellow Pearl was 0.04 mg/kg, making it a low-accumulation S. lycopersicum variety suitable for promoting cultivation in Cd-contaminated soil at 0.6 mg/kg. In conclusion, the Cd accumulation in the fruit of Yellow Pearl is significantly lower than that of Yellow Cherry and even below the Cd limit value for fresh vegetables specified in GB2762-2017. Therefore, Yellow Pearl can be grown as edible crops in soils with Cd concentrations ≤0.6 mg/kg. Furthermore, Yellow Cherry demonstrate strong Cd tolerance and can be used for the remediation of Cd-contaminated soils.