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Contrast-induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine-based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK-2 cells. BBR reduced ioversol-induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p-Akt and p-Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol-induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine-based contrast agents.
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Berberina , Yodo , Enfermedades Renales , Ácidos Triyodobenzoicos , Humanos , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt , Berberina/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Medios de Contraste/efectos adversos , Ratas Sprague-Dawley , Enfermedades Renales/tratamiento farmacológico , Yodo/efectos adversos , ApoptosisRESUMEN
BACKGROUND AND OBJECTIVES: Due partly to an ageing population, China faces an increasingly dire blood shortage crisis requiring greater voluntary blood donations. A better understanding of blood donation preferences can inform blood donation policies and potentially increase donations. We used an online survey and discrete choice experiment to achieve our study objective: identify the most influential structural facilitators and barriers to voluntary blood donation in China. MATERIALS AND METHODS: First, we identified six structural attributes (travel time, venue, donation volume, paid leave, scheduling and gifts) that were hypothesized to influence voluntary blood donation; attribute selection was based on a literature review and qualitative interviews. Second, a d-efficient design with 36 choice sets and 9 blocks was developed. Participants were asked to complete four choice sets, and in each choice set, they were asked to choose from three options: two voluntary blood donation scenarios and a 'Do not donate blood' option. Study participants were recruited through an online survey platform company in China. Voluntary blood donation preferences and preferences by blood donation history were estimated with random-parameter logit models and interaction terms. RESULTS: In 2022, 1185 individuals enrolled in the study. Most participants had college education (92%). Generally, participants preferred longer paid leave, lower blood donation volumes and gifts after donation. Based on interaction analyses, experienced and inexperienced donors exhibited similar preferences. CONCLUSION: Campaigns to increase voluntary blood donation rates in China should consider implementing paid leave after voluntary blood donation, lower blood donation volumes and small gifts conferred after donation.
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Donantes de Sangre , Humanos , Donantes de Sangre/psicología , China , Masculino , Femenino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Adolescente , Conducta de Elección , Adulto Joven , Anciano , Donación de SangreRESUMEN
As a vital pathway for cellular energy production, mitochondrial fatty acid ß-oxidation (FAO) is essential in regulating immune responses to bacterial pathogens and maintaining intracellular homeostasis in vertebrates. However, the specific role of FAO in antiviral innate immune response in macrophages remains insufficiently understood. In this study, virus infection simulated by poly(I:C) inhibited FAO, as indicated by the reduced expression of FAO-related genes and proteins in the head kidney of large yellow croaker, with similar results observed in poly(I:C)-stimulated macrophages. Then, inhibition of FAO by supplementary mildronate in vivo and etomoxir treatment in vitro revealed varying increases in the mRNA expression of antiviral innate immune response genes after stimulated by poly(I:C) in the head kidney and macrophages. Notably, etomoxir significantly facilitated the transcriptional up-regulation of the IFNh promoter by IRF3. Moreover, inhibiting FAO by knockdown of cpt1b promoted antiviral innate immune response triggered by poly(I:C) in macrophages. Conversely, activating FAO through overexpression of cpt1b or cpt2 significantly reduced the mRNA levels of antiviral response genes in macrophages stimulated by poly(I:C). Unlike etomoxir, cpt1b overexpression inhibited the transcriptional up-regulation of the IFNh promoter by IRF3. Furthermore, in vivo dietary palm oil feeding and in vitro exposure to palmitic acid inhibited the antiviral innate immune response triggered by poly(I:C) in the head kidney and macrophages, respectively. These effects were partly associated with FAO activation, as evidenced by etomoxir. In summary, this study elucidates FAO's critical role in regulating antiviral innate immune response in head kidney macrophages. These findings not only deepen insights into the interaction between metabolic remodeling and host immune responses, but also offer valuable guidance for developing nutritional strategies to improve antiviral immunity in aquaculture.
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In hospitals, contrast-induced acute kidney injury (CI-AKI) is a major cause of renal failure. This study evaluates berberine's (BBR) renal protection and its potential HDAC4 mechanism. CI-AKI in rats was induced with 10 mL kg-1 ioversol. Rats were divided into five groups: Ctrl, BBR, CI-AKI, CI-AKI + BBR, and CI-AKI + Tasq. The renal function of CI-AKI rats was determined by measuring serum creatinine and blood urea nitrogen. Histopathological changes and apoptosis of renal tubular epithelial cells were observed by HE and terminal deoxynucleotidyl transferase (TdTase)-mediated dUTP-biotin nick end labeling (TUNEL) staining. Transmission electron microscopy was used to observe autophagic structures. In vitro, a CI-AKI cell model was created with ioversol-treated HK-2 cells. Treatments included BBR, Rapa, HCQ, and Tasq. Analyses focused on proteins and genes associated with kidney injury, apoptosis, autophagy, and the HDAC4-FoxO3a axis. BBR showed significant protective effects against CI-AKI both in vivo and in vitro. It inhibited apoptosis by increasing Bcl-2 protein levels and decreasing Bax levels. BBR also activated autophagy, as indicated by changes in autophagy-related proteins and autophagic flux. The study further revealed that the contrast agent ioversol increased the expression of HDAC4, which led to elevated levels of phosphorylated FoxO3a (p-FoxO3a) and acetylated FoxO3a (Ac-FoxO3a). However, BBR inhibited HDAC4 expression, resulting in decreased levels of p-FoxO3a and Ac-FoxO3a. This activation of autophagy-related genes, regulated by the transcription factor FoxO3a, played a role in BBR's protective effects. BBR, a traditional Chinese medicine, shows promise against CI-AKI. It may counteract CI-AKI by modulating HDAC4 and FoxO3a, enhancing autophagy, and limiting apoptosis.
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Lesión Renal Aguda , Berberina , Ácidos Triyodobenzoicos , Animales , Ratas , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Apoptosis , Autofagia , Berberina/farmacología , Histona DesacetilasasRESUMEN
Contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN), has become the third leading cause of iatrogenic AKI. Serum creatinine (Scr) is currently used in CIN clinical diagnosis. Patients with increased Scr have developed severe kidney injury, so there is an urgent need to find a bio-marker for CIN early diagnosis. To investigate the changes in circulating microRNA-188-5p (miR-188-5p) after coronary angiography and its predictive value for the CIN occurrence, miR-188-5p expression in CIN rats from the GEO database and CIN patients and control patients from Lianshui People's Hospital was analyzed. The results showed that miR-188-5p expression in plasma and renal was higher in CIN group than in control group. Further, a total of 36 CIN patients and 108 non-CIN patients were included. There were significant differences in age, hypertension, diabetes, and contrast agent dosage. After 12 h of contrast agent application, circulating miR-188-5p expression in CIN group was higher than control group. Univariate and multivariate logistic regression analysis showed that age, hypertension, diabetes, contrast media dosage and postoperative miR-188-5p expression were closely related to CIN occurrence. For in vitro experiments, intracellular miR-188-5p expression was decreased with ioversol treatment, while miR-188-5p expression in supernatant was increased. To explore the potential mechanism of miR-188-5p in CIN, HK-2 cells were treated with NC mimic, ioversol, or miR-188-5p mimic. The results showed that the application of miR-188-5p mimic reduced apoptosis, reactive oxygen species and MDA, enhanced SOD and GSH contents. Further, it was confirmed that mRNA and protein levels of PTEN were up-regulated in ioversol-treated HK-2 cells, and down-regulated after miR-188-5p administration. Dual-luciferase reporter gene assay confirmed that PTEN was direct target gene of miR-188-5p. Above results suggest that circulating miR-188-5p has the potential to serve as a predictor of CIN.
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The structure and electronic and spintronic properties of two-dimensional (2D) ternary compounds ABC (A = Sb, Bi; B = Se, Te; C = Br; I) monolayers are investigated using the first-principles method. The ABC monolayers possess typical Janus structures with a considerable potential gradient normal to the surface, inducing intrinsic Rashba spin splitting (RSS) at the conduction band minimum near the Γ point. Among them, the splitting strength of the BiSeI monolayer is the largest and its Rashba coefficient can reach 1.84 eV Å. The projected energy band of the BiSeI monolayer suggests that the RSS state is mainly rooted in the Bi-pz orbital. The RSS strength can be modulated by applying the in-plane strain. The tensile strain can improve the RSS strength, which is ascribed to the increase of the potential gradient normal to the surface. These results indicate that these 2D ternary compounds have great potential for application in tunable spintronic devices.
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OBJECTIVE: To evaluate the association between plasma transfusion and bleeding complications in critically ill patients with an elevated international normalized ratios undergoing invasive procedures. METHODS: A retrospective study was conducted to evaluate a consecutive sample of critically ill adult patients undergoing invasive procedures (N = 487) with an international normalized ratio ≥ 1.5 between January 1, 2019 and December 31, 2019. Among the followed patients, 125 were excluded due to incomplete case records and 362 were finally included in this investigation. The exposure was whether plasma had been transfused within 24 h before the invasive procedure. The primary outcome was the occurrence of postprocedural bleeding complications. Secondary outcomes included transfusion of red blood cells within 24 h of the invasive procedure, and additional patient-important outcomes such as mortality and length of stay. Tests were performed with univariate and propensity-matched analyses. RESULTS: Of the 362 study participants, 99 (27.3 %) received a preprocedural plasma transfusion. In the propensity score-matched analysis, the rate of the occurrence of postprocedural bleeding complications between two groups was not statistically different (OR, 0.605[95 % CI, 0.341-1.071]; P = .085). The rate of postoperative red blood cell transfusion in the plasma transfusion group was higher than that in the non-plasma transfusion group (35.5 % vs 21.5 %; P < .05). No statistically significant difference in mortality was observed between the two groups (29.0 % vs 31.6 %; P = .101). CONCLUSIONS: Prophylactic plasma transfusion failed to reduce postprocedural bleeding complications in ill critically patients with a coagulopathy. Meanwhile, it was associated with increased red blood cell transfusion after invasive procedures. Findings suggest that abnormal preprocedural international normalized ratios should be managed more conservatively.
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Transfusión Sanguínea , Enfermedad Crítica , Adulto , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Enfermedad Crítica/terapia , Relación Normalizada InternacionalRESUMEN
BACKGROUND: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. METHODS: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. DISCUSSION: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .
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Sepsis , Humanos , Estudios Multicéntricos como Asunto , Puntuaciones en la Disfunción de Órganos , Reacción en Cadena de la Polimerasa , Ensayos Clínicos Pragmáticos como Asunto , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma. METHODS: A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion. RESULTS: Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r = 0.3375, p = 0.04). A possible estimation equation was as follows: Log10 (Reduction in viral load) = 0.18 + 0.001 × (Log2 S-RBD antibody titer × Plasma infusion volume) (r = 0.424, p = 0.009). In a single case, the viral nucleic acid persisted 14 days after the fourth plasma infusion. CONCLUSIONS: This study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.
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COVID-19 , Ácidos Nucleicos , Anticuerpos Antivirales , COVID-19/terapia , Niño , Humanos , Inmunización Pasiva , SARS-CoV-2 , Carga Viral , Sueroterapia para COVID-19RESUMEN
PURPOSE: To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). METHODS: One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. RESULTS: Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P = 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P < 0.05). In multivariate analysis, TLR (P < 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P < 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. CONCLUSION: Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Renales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
PURPOSE: Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[18F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Ninety patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[18F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy. RESULTS: Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value. CONCLUSIONS: Our findings demonstrated that 2-[18F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Renales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Microambiente TumoralRESUMEN
Metal sulfides are often used as cathode materials for lithium-ion batteries (LIBs) owing to their high theoretical specific capacity; however, excessively fast capacity decay during charging/discharging and rapid shedding during cycling limits their practical application in batteries. In this study, we proposed a strategy using plasma treatment combined with the solvothermal method to prepare cobalt sulfide (Co1-xS)-carbon nanofibers (CNFs) composite. The plasma treatment could introduce oxygen-containing polar groups and defects, which could improve the hydrophilicity of the CNFs for the growth of the Co1-xS, thereby increasing the specific capacity of the composite electrode. The results show that the composite electrode present a high discharge specific capacity (839 mAh g-1at a current density of 100 mA g-1) and good cycle stability (the capacity retention rate almost 100% at 2000 mA g-1after 500 cycles), attributing to the high conductivity of the CNFs. This study proves the application of plasma treatment and simple vulcanization method in high-performance LIBs.
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To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 µM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC50 = 2-3 µM for NO inhibition), amongst them, compound 5r also inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner. In cisplatin-induced AKI mice model, compound 5r significantly reduced the level of pro-inflammatory factors, ameliorated the pathological damage of kidney tissue, and maintained the normal metabolic capacity.
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Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/síntesis química , Urea/análogos & derivados , Urea/síntesis química , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Cisplatino/toxicidad , Diseño de Fármacos , Ácido Glicirretínico/farmacología , Inflamación/tratamiento farmacológico , Ratones , Células RAW 264.7 , Urea/farmacologíaRESUMEN
We recently reported that epiblast stem cells (EpiSCs)-like cells could be derived from preimplantation embryos (named as AFSCs). Here, we established AFSCs from pre-implantation embryos of multiple mouse strains and showed that unlike EpiSCs, the derivation efficiency of AFSCs was affected by the genetic background. We then used AFSCs lines to dissect the roles of Activin A (Act A) and basic fibroblast growth factor and reported that Act A alone was capable of maintaining self-renewal but not developmental potential in vivo. Finally, we established a novel experimental system, in which AFSCs were efficiently converted to multipotent progenitor stem cells using Act A and bone morphogenetic protein 4 (named as ABSCs). Importantly, these ABSCs contributed to neural mesodermal progenitors and lateral plate mesoderm in postimplantation chimeras. Taken together, our study established a robust experimental system for the generation of specific multipotent progenitor stem cells that was self-renewable and capable of contributing to embryonic and extra-embryonic tissues.
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Activinas/farmacología , Estratos Germinativos/efectos de los fármacos , Células Madre Multipotentes/efectos de los fármacos , Células Madre Pluripotentes/efectos de los fármacos , Activinas/metabolismo , Animales , Blastocisto/efectos de los fármacos , Blastocisto/metabolismo , Proteína Morfogenética Ósea 4/efectos de los fármacos , Proteína Morfogenética Ósea 4/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Desarrollo Embrionario/efectos de los fármacos , Células Madre Embrionarias/efectos de los fármacos , Células Madre Embrionarias/metabolismo , Estratos Germinativos/crecimiento & desarrollo , Ratones , Células Madre Pluripotentes/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
N6-methyladenosine (m6 A) RNA modification can alter gene expression and function by regulating RNA splicing, stability, translocation, and translation. Deregulation of m6 A has been involved in various types of cancer. However, its implications in non-small-cell lung cancer (NSCLC) are mostly unknown. This posttranscriptional modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6 A binding proteins. In this study, we comprehensively investigated the contributions and prognostic values of 13 common m6 A RNA modification regulators using The Cancer Genome Atlas database. We found that the expression levels of most of the studied genes were significantly altered in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Using consensus clustering, the gene-expression profiles of 13 m6 A regulators could classify patients with LUAD into two subgroups with significantly distinct clinical outcomes, but not the LUSC cohort or the combination of the two cohorts. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were applied to explore differential signaling pathways and cellular processes between the two LUAD subgroups. Moreover, we found that this gene-expression signature could better predict prognosis in the late-stage (III + IV) than in the early-stage (I + II) LUAD. Finally, we developed an optimal prognostic gene signature by using the least absolute shrinkage and selection operator Cox regression algorithm and compute risk score. In conclusion, our study unveiled the implication of m6 A RNA modification regulators in NSCLC and identified the m6 A gene expression classifiers for predicting the prognosis of NSCLC.
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Adenosina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN/genética , ARN/genética , Adenosina/genética , Adenosina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Metiltransferasas/genética , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Acute lung injury (ALI), which is induced by numerous pathogenic factors, especially sepsis, can generate alveolar damage, pulmonary edema and vascular hyper-permeability ultimately leading to severe hypoxemia. Fibroblast growth factor-2 (FGF2) is an important member of the FGF family associated with endothelial cell migration and proliferation, and injury repairment. Here, we conducted this study aiming to evaluate the therapeutic effect of FGF2 in sepsis-induced ALI. METHODS: Recombinant FGF2 was abdominally injected into septic mice induced by cecal ligation and puncture (CLP), and then the inflammatory factors of lung tissue, vascular permeability and lung injury-related indicators based on protein levels and gene expression were detected. In vitro, human pulmonary microvascular endothelial cells (HPMEC) and mouse peritoneal macrophages (PMs) were challenged by lipopolysaccharides (LPS) with or without FGF2 administration in different groups, and then changes in inflammation indicators and cell permeability ability were tested. RESULTS: The results revealed that FGF2 treatment reduced inflammation response, attenuated pulmonary capillary leakage, alleviated lung injury and improved survival in septic mice. The endothelial injury and macrophages inflammation induced by LPS were inhibited by FGF2 administration via AKT/P38/NF-κB signaling pathways. CONCLUSION: These findings indicated a therapeutic role of FGF2 in ALI through ameliorating capillary leakage and inflammation.
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Permeabilidad Capilar/genética , Factor 2 de Crecimiento de Fibroblastos/genética , Sepsis/etiología , Animales , Biomarcadores , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Inmunohistoquímica , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/efectos adversos , Masculino , Ratones , FN-kappa B/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sepsis/metabolismo , Sepsis/mortalidad , Sepsis/patología , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Recently two dimensional (2D) metal-organic frameworks have been successfully used as electrocatalysts, which exhibited a high catalytic activity. Herein, we investigated the catalytic mechanism of the oxygen reduction reaction (ORR) on M3(hexaiminotriphenylene)2 (M3(HITP)2, M = Ni, Cu) in an acidic medium using the density functional theory (DFT) method. The results indicate that the first electron transfer (ET) to nonadsorbed O2 is a process of long-range ET on the outer Helmholtz plane (i.e. the ET-OHP mechanism). On the surface of M3(HITP)2 (M = Ni, Cu), both the 2e reduction pathway and the 4e reduction pathway are feasible, while the 2e pathway to form H2O2 is more favorable. In the several competing reactions for the 4e reduction pathway on M3(HITP)2, the favorable path is OOH* â O* + H2O â OH* â H2O. Our study provides theoretical guidance for gaining deeper insights into the reaction mechanism of the ORR on M3(HITP)2 (M = Ni, Cu) catalysts.
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OBJECTIVE: The effect of flavonoids from alfalfa on the microbial flora was determined using molecular techniques of 16S ribosome deoxyribonucleic acid (rDNA) analysis. METHODS: Four primiparous Holstein heifers fitted with ruminal cannulas were used in a 4×4 Latin square design and fed a total mixed ration to which alfalfa flavonoids extract (AFE) was added at the rates of 0 (A, control), 20 (B), 60 (C), or 100 (D) mg per kg of heifer BW. RESULTS: The number of operational taxonomic units in heifers given higher levels of flavonoid extract (C and D) was higher than for the two other treatments. The Shannon, Ace, and Chao indices for treatment C were significantly higher than for the other treatments (p<0.05). The number of phyla and genera increased linearly with increasing dietary supplementation of AFE (p<0.05). The principal co-ordinates analysis plot showed substantial differences in the microbial flora for the four treatments. The microbial flora in treatment A was similar to that in B, C, and D were similar by the weighted analysis. The richness of Tenericutes at the phylum level tended to increase with increasing AFE (p = 0.10). The proportion of Euryarchaeota at the phylum level increased linearly, whereas the proportion of Fusobacteria decreased linearly with increasing AFE supplementation (p = 0.04). The percentage of Mogibacterium, Pyramidobacter, and Asteroleplasma at the genus level decreased linearly with increasing AFE (p<0.05). The abundance of Spirochaeta, Succinivibrio, and Suttonella at the genus level tended to decrease linearly with increasing AFE (0.05
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Nanotubes are one of the most promising functional materials in nanotechnology. Silicon nanotubes (SiNTs) have been experimentally validated; they are unique puckered nanotubular structures unlike carbon nanotubes (CNTs). Although the electronic and optical properties of SiNTs have been previously studied, their structure-related capability for electron transport has not been investigated. Here we report a comparative study of the intrinsic electronic and transport properties of four pairs of SiNTs and CNTs (one armchair nanotubes (3,3) and three zigzag nanotubes (5,0), (6,0) and (7,0)) using density functional theory (DFT) combined with the nonequilibrium Green's function (NEGF) method. All our investigated systems of SiNTs and CNTs are conductors. Both the armchair SiNTs and CNTs possess superior electron transport performance to their zigzag counterparts. Compared with CNTs, SiNTs have more advantages in the high bias voltage region. Especially, Si(3,3) possesses around double the potential charge capacity of C(3,3) under the bias voltage of 2.0 V. In particular, the CNT(6,0) exhibits distinct negative differential resistance (NDR) behavior and the peak-valley ratio (PVR) for C(6,0) is about 1.2.
RESUMEN
Quantum chemical calculations were performed to explore the structural and electronic properties of the two polyoxoaurates, [Au(III)4As(V)4O20](8-) (Au4As4) and [Au(III)4Se(IV)4O16](4-) (Au4Se4), known to date, and a number of hypothetical polyoxoaurate derivatives comprising heteroatoms different from arsenic and selenium (namely, Si, Ge and P). In addition, the interactions of [Au(III)4X4Om](n-) (X = As, Se) with alkali-metal cations (Li(+), Na(+), K(+) and Rb(+)) are also analysed. The studies suggest that the geometry structure, electronic properties and nucleophilicity of oxygen atoms of these polyoxoaurates are tuned by the size or electronegativity of the heteroatoms (Si, Ge, P, As and Se). Then, the geometry of [Au(III)4X4Om](n-) (X = As and Se) coordinating with alkali cations from Li(+) to Rb(+) and the complexation energy between [Au(III)4X4Om](n-) and alkali cations were compared. The results show that the stability and electronic structure of heteropolyoxoaurates depend on the entrapped cations. On the basis of the complexation energy, it can be concluded that the ion-pairing effect in arsenate-capped oxoaurate is stronger than that in selenite-capped oxoaurate. These heteropolyoxoaurates are expected to play a role in aqueous behaviour, self-assembly characteristics of polyoxoaurates, ion recognition, selectivity studies and may exhibit potential guest-switchable redox properties.