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AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.
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Diabetes Gestacional , Ácido Fólico , Metilenotetrahidrofolato Reductasa (NADPH2) , Humanos , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/metabolismo , Embarazo , Ácido Fólico/sangre , Estudios Prospectivos , Adulto , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Biomarcadores/sangre , Estudios de Seguimiento , Ferredoxina-NADP Reductasa/genética , Genotipo , China/epidemiología , Pronóstico , Segundo Trimestre del Embarazo/sangre , Homocisteína/sangre , Homocisteína/metabolismoRESUMEN
BACKGROUND: Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. METHODS: Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1ß, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. RESULTS: The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin ß1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin ß1-dependent manner, while both plexin C1 and integrin ß1 contributed to Sema7A-induced HCAEC hyperpermeability. CONCLUSIONS: Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin ß1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
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Antígenos CD , Integrina beta1 , Síndrome Mucocutáneo Linfonodular , Receptores de Superficie Celular , Semaforinas , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteína ADAM17/metabolismo , Antígenos CD/metabolismo , Permeabilidad Capilar , Estudios de Casos y Controles , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Proteínas Ligadas a GPI , Inflamación/metabolismo , Integrina beta1/metabolismo , Monocitos/metabolismo , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/sangre , Proteínas del Tejido Nervioso/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/sangre , Semaforinas/metabolismo , Semaforinas/sangreRESUMEN
BACKGROUND: Parental exposure to rare earth elements (REEs) could increase the risk of premature rupture of membranes, a major cause of spontaneous preterm birth (SPB). In addition, different subtypes of SPB, such as spontaneous preterm labor (SPL) and preterm premature rupture of membranes (PPROM), may have different susceptibility to environmental exposure. Therefore, we investigated the potential associations between REE exposure in different trimesters and SPB and its subtypes. METHODS: A nested case-control study was performed. We included 244 women with SPB as cases and 244 women with full-term delivery as controls. The plasma concentrations of light REEs were measured in the first and third trimesters. Logistic regression was used to analyze the associations between single REE levels and SPB, and Bayesian kernel machine regression (BKMR) was used to analyze the mixed-exposure effect. RESULTS: Exposure to light REEs was associated with SPB and its subtypes only in the third trimester. Specifically, the intermediate- and highest-tertile concentration groups of La and the highest-tertile concentration group of Sm were associated with an increased risk of SPL, with adjusted odds ratios (AORs) of 2.00 (95% CIs: 1.07-3.75), 1.87 (95% CIs: 1.01-3.44), and 1.82 (95% CIs: 1.00-3.30), respectively. The highest-tertile concentration group of Pr was associated with an increased risk of PPROM, with an AOR of 1.69 (95% CIs: 1.00-2.85). Similar results were also found in BKMR models. CONCLUSIONS: La and Sm levels in plasma may be associated with the risk of SPL, and Pr levels in plasma may be associated with the risk of PPROM.
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Nacimiento Prematuro , Recién Nacido , Femenino , Humanos , Nacimiento Prematuro/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Beijing/epidemiología , Teorema de BayesRESUMEN
Paleozoic and Precambrian sedimentary successions frequently contain massive dolomicrite [CaMg(CO3)2] units despite kinetic inhibitions to nucleation and precipitation of dolomite at Earth surface temperatures (<60 °C). This paradoxical observation is known as the "dolomite problem." Accordingly, the genesis of these dolostones is usually attributed to burial-hydrothermal dolomitization of primary limestones (CaCO3) at temperatures of >100 °C, thus raising doubt about the validity of these deposits as archives of Earth surface environments. We present a high-resolution, >63-My-long clumped-isotope temperature (TΔ47) record of shallow-marine dolomicrites from two drillcores of the Ediacaran (635 to 541 Ma) Doushantuo Formation in South China. Our T∆47 record indicates that a majority (87%) of these dolostones formed at temperatures of <100 °C. When considering the regional thermal history, modeling of the influence of solid-state reordering on our TΔ47 record further suggests that most of the studied dolostones formed at temperatures of <60 °C, providing direct evidence of a low-temperature origin of these dolostones. Furthermore, calculated δ18O values of diagenetic fluids, rare earth element plus yttrium compositions, and petrographic observations of these dolostones are consistent with an early diagenetic origin in a rock-buffered environment. We thus propose that a precursor precipitate from seawater was subsequently dolomitized during early diagenesis in a near-surface setting to produce the large volume of dolostones in the Doushantuo Formation. Our findings suggest that the preponderance of dolomite in Paleozoic and Precambrian deposits likely reflects oceanic conditions specific to those eras and that dolostones can be faithful recorders of environmental conditions in the early oceans.
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A Gram-negative, rod-shaped aerobic bacterium designated as strain 2R12T was isolated from the rhizosphere soil of Hosta plantaginea. Phylogenetic analyses based on the 16S rRNA gene revealed that strain 2R12T should be assigned to the genus Chitinophaga with the highest sequence similarity to Chitinophaga arvensicola DSM 3695T (99.1â%) and Chitinophaga ginsengisegetis DSM 18108T (98.6â%). The major fatty acids of strain 2R12T (>10â%) were iso-C15â:â0, C16â:1 ω5c and iso-C17â:â0 3-OH. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and five unidentified lipids. The predominant respiratory quinone was MK-7. The genomic DNA G+C content was 46.1âmol%. The average nucleotide identity values of strain 2R12T with C. arvensicola DSM 3695T and C. ginsengisegetis DSM 18108T were 77.9 and 78.8â%, respectively, while in silico DNA-DNA hybridization values for strain 2R12T with these strains were 22.8 and 23.3â%, respectively. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain 2R12T represents a novel species in the genus Chitinophaga, for which the name Chitinophaga hostae sp. nov. is proposed. The type strain is 2R12T (=ACCC 61757T=JCM 34719T).
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Gammaproteobacteria , Hosta , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/genética , Hosta/genética , Filogenia , ARN Ribosómico 16S/genética , Rizosfera , Análisis de Secuencia de ADN , Suelo , Microbiología del Suelo , Vitamina K 2RESUMEN
BACKGROUND: Patients with nonmetastatic pT3-4 colon cancers are prone to develop metachronous peritoneal carcinomatosis (mPC). Risk factors for mPC and the influence of mutant kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma rat sarcoma (NRAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and DNA mismatch repair (MMR) status on mPC remain to be described in these patients. METHOD: All enrolled patients were identified from the prospectively collected colorectal cancer database of a tertiary referral hospital between 2013 and 2018. Multivariate analysis was used to identify risk factors associated with mPC. RESULTS: Of the 1689 patients with nonmetastatic pT3-4 colon carcinoma, 8.4% (142/1689) progressed to mPC. Endoscopic obstruction (HR = 3.044, p < 0.001), elevated CA125 (HR = 1.795, p = 0.009), pT (T4a vs. T3, HR = 2.745, p < 0.001; T4b vs. T3, HR = 3.167, p = 0.001), pN (N1 vs. N0, HR = 2.592, p < 0.001; N2 vs. N0, HR = 4.049, p < 0.001), less than 12 lymph nodes harvested (HR = 2.588, p < 0.001), mucinous or signet ring cell carcinoma (HR = 1.648, p = 0.038), perineural invasion (HR = 1.984, p < 0.001), and adjuvant chemotherapy (HR = 1.522, p = 0.039) were strongly related to mPC but that mutant KRAS/NRAS/BRAF and MMR status was not associated with mPC. CONCLUSION: This study identified the high-risk factors for mPC in patients with nonmetastatic pT3-4 colon carcinoma, and these factors should be considered in selective preventive therapy and close follow-up for patients subsequently deemed to have high risk for mPC.
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Carcinoma de Células en Anillo de Sello , Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias Peritoneales , Animales , Carcinoma de Células en Anillo de Sello/patología , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/patología , Ratones , Mutación , Estadificación de Neoplasias , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Factores de RiesgoRESUMEN
This study determined the chemosensitizing potential of ginsenoside Rg1 in triple-negative MDA-MB-231 breast cancer cell lines. Ginsenoside Rg1 (10 µM) treated breast cancer cells were exposed to 8 nM of doxorubicin, and the chemosensitizing potential was measured by cell-based assays. Ginsenoside Rg1 (10 µM) treatment lowered the doxorubicin IC50 value to 0.01 nM. Furthermore, the ginsenoside pretreatment augments doxorubicin-mediated reactive oxygen species (ROS) generation and subsequent alterations of mitochondrial membrane potential in MDA-MB-231 cell lines. The alkaline comet assay results illustrated an increased % tail DNA during ginsenoside Rg1 plus doxorubicin treatment than doxorubicin alone treatment. In addition, the number of apoptotic cells was also increased in ginsenoside Rg1 plus doxorubicin-treated cells. Furthermore, the polymerase chain reaction array results illustrate activation of mitogen-activated protein kinase (MAPK) gene expression (AKT, ERK, and MAPK) during doxorubicin alone treatment and it has been attenuated by ginsenoside Rg1 pretreatment. Moreover, ginsenoside Rg1 treatment before doxorubicin activates the DNA damage response elements (ATM, H2AX, RAD51, and XRCC1) and subsequent apoptosis-related gene expression (p21, TP53. APAF1, Bax, CASP3, and CASP9) patterns in MDA-MB-231 cell lines. The ginsenoside Rg1 plus doxorubicin combination shows less cytotoxicity and ROS generation in MDA10A normal breast cancer cell lines. Therefore, the present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.
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Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Doxorrubicina/farmacología , Ginsenósidos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , HumanosRESUMEN
Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen's Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.
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Antineoplásicos , Mucositis , Estomatitis , Animales , Ratas , Ratones , Humanos , Conejos , Porcinos , Pez Cebra , Reproducibilidad de los Resultados , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Irinotecán/efectos adversos , Fluorouracilo/toxicidad , Antineoplásicos/toxicidad , Estomatitis/tratamiento farmacológico , Metotrexato/toxicidadRESUMEN
A new mechanism between the temperature sensitivity and the length ratio of PMMA coating to no-core fiber (NCF) is reported to realize an optical fiber temperature sensor with ultra-high sensitivity and compact size by PMMA-coated no-core fiber. By both theory and experiment, it is found that the sensitivity has a linear response to the length ratio of PMMA coating to NCF rather than the conventional viewpoint that it depends on the length of PMMA. Based on this conclusion and the high thermo-optic coefficient of PMMA, the temperature sensitivity is significantly enhanced as high as -9.582â nm/â through a simple, compact, and inexpensive sensor with 5â mm NCF and 3â mm PMMA coating. Our work opens a new avenue of a significant increase in the detection sensitivity of miniaturized fiber temperature sensors.
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Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the pathogenesis of ADS and puts an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with ß-estradiol (ß-E2) presented stronger proliferative and pro-angiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins. Meanwhile, these promoting effects were partially abrogated by Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of OV-Talin1 plus ß-E2 treatment. Results from the xenograft nude mice model showed that the hypodermic endometrial lesions from co-intervention group had the highest mean weight and volume, compared with that of individual OV-Talin1 or ß-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated the most in the co-intervention group. Our findings unveiled that overexpressed Talin1 might cooperate withß-E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.
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Adenomiosis/fisiopatología , Endometrio/patología , Células del Estroma/fisiología , Talina/fisiología , Adenocarcinoma , Adenomiosis/genética , Adenomiosis/metabolismo , Animales , División Celular/efectos de los fármacos , Línea Celular Tumoral , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Neoplasias Endometriales , Estradiol/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Miometrio/patología , Neovascularización Patológica/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas Recombinantes/metabolismo , Organismos Libres de Patógenos Específicos , Células del Estroma/efectos de los fármacos , Talina/biosíntesis , Talina/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Let-7a is a small non-coding RNA that has been found to take part in cell proliferation and apoptosis. The hippo-YAP1 axis, known as a tumour suppressor pathway, also plays an important role in cell proliferation and apoptosis. YAP1, TAZ, and phospho-YAP1 play key roles in actions of the hippo-YAP1 axis. Adenomyosis (ADS) is a proliferative disease leading to a large uterus in patients with prolonged illness. Abnormal proliferation of smooth muscle cells (SMCs) in the uterine endometrial-myometrial junctional zone (JZ) is an important reason for developing ADS. This study aimed to explore the expression levels of let-7a and components of the hippo-YAP1 axis in SMCs in the uterine endometrial-myometrial JZ in ADS and to explore the roles of let-7a and the hippo-YAP1 axis of JZ SMC proliferation and apoptosis in ADS. METHODS: We collected JZ tissues for the primary culture of SMCs from 25 women diagnosed with ADS and 27 women without ADS. We used quantitative real-time polymerase chain reaction and western blotting to measure the mRNA and protein expression levels of let-7a, YAP1, TAZ, and phospho-YAP1 in ADS JZ SMCs. A CCK-8 assay and flow cytometry analysis of apoptosis were utilized to test the proliferation and apoptosis of JZ SMCs. The let-7a overexpression lentiviral vector GV280 was used to increase the expression level of let-7a. We added verteporfin to block the phosphorylation of components of the hippo-YAP1 axis. RESULTS: We found that the let-7a level was decreased, while the YAP1 and TAZ levels were increased in ADS JZ SMCs. Upregulated let-7a affected the expression levels of components of the hippo-YAP1 axis, accelerated apoptosis, and inhibited proliferation in JZ SMCs. Furthermore, accumulated YAP1 led to increasing proliferation of JZ SMCs after verteporfin treatment to block the phosphorylation of components of the hippo-YAP1 axis. If components of the hippo-YAP1 axis were unphosphorylated, upregulated let-7a could not inhibit the proliferation of ADS JZ SMCs. Upregulated let-7a could not activate the hippo-YAP1 axis in verteporfin treatment. CONCLUSIONS: Our findings suggest that the let-7a and hippo-YAP1 axis may act as important regulators of JZ SMCs proliferation, and upregulated let-7a may be an effective method to treat ADS.
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Adenomiosis/genética , Endometrio/metabolismo , MicroARNs/genética , Miocitos del Músculo Liso/metabolismo , Miometrio/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/genética , Proteínas Señalizadoras YAP/genética , Adenomiosis/metabolismo , Adulto , Apoptosis/genética , Estudios de Casos y Controles , Proliferación Celular/genética , Femenino , Vía de Señalización Hippo , Humanos , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Proteínas Señalizadoras YAP/metabolismoRESUMEN
Disrupted endothelial permeability plays a crucial role in the vasculitis pathogenesis of Kawasaki disease (KD), which leads to pathological vascular leak and facilitates inflammatory cell infiltration in vascular lesions; however, the mechanisms involved in the development of endothelial barrier dysfunction during KD vasculitis are still largely unclear. Here, we found that sera from patients with KD can induce endothelial cell (EC) hyperpermeability compared to sera from healthy controls. We observed that serum vascular endothelial growth factor (VEGF) levels were increased in KD patients and sera from KD patients upregulated the expression of VEGF receptor 2 (VEGFR2) and neuropilin-1 (NRP1) in human coronary artery endothelial cells (HCAECs). Intriguingly, compared with silence of VEGFR2 in HCAECs, NRP1 silence resulted in a marked decrease in EC permeability. Furthermore, soluble NRP1 (sNRP1) remarkably reduced the stimulation of EC permeability by sera from KD patients compared with bevacizumab treatment. Importantly, we showed that besides VEGF, angiopoietin-like-4 (ANGPTL4), a NRP1-binding vasoactive factor, was also increased in KD and contributed to the EC permeability in KD conditions. In addition, levels of both ANGPTL4 and VEGF were inversely correlated with albumin levels in the serum of KD patients. Collectively, the data demonstrated that overexpressed NRP1, along with upregulated VEGFR2, in HCAECs treated with KD sera promotes endothelial permeability via interaction with the increased ANGPTL4 and VEGF in KD. Neutralization of hyperpermeability factors by sNRP1 may be a novel therapeutic strategy for KD vasculitis.
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Síndrome Mucocutáneo Linfonodular , Neuropilina-1/metabolismo , Factor A de Crecimiento Endotelial Vascular , Proteína 4 Similar a la Angiopoyetina , Células Endoteliales/metabolismo , Humanos , Permeabilidad , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Crecimiento Endotelial VascularRESUMEN
RATIONALE: Carbonate clumped isotope (Δ47 ) thermometry examines the temperature-dependent excess abundance of the 13 C-18 O bond in the carbonate lattice. Inconsistent temperature calibrations and standard values have been reported among laboratories, which has led to the use of equilibrated gases and carbonate standards for standardization. Furthermore, different acid fractionation factors and isotopic parameter sets have been proposed for improving inter-laboratory data comparability. However, few long-term datasets have been generated to explore the effects of these factors on the long-term reproducibility of Δ47 data within a laboratory. METHODS: Four standards (ISTB-1, NBS-19, GBWO4416, and GB04417) were analyzed as unknowns by isotope ratio mass spectrometry from 2015 to 2019. The values of Δ47 were calibrated using the ETH standards. We investigated the Assonov, Brand, and Gonfiantini isotope parameter sets for carbon and oxygen isotopes, as well as two correction schemes of equilibrated gas and carbonate standardization, using the same sample measurements to determine which procedures enhanced reproducibility. ISTB-1 (calcite) and ZK312-346W (dolomite) were measured to determine the 90°C acid fractionation factor. RESULTS: The corrected 90°C acid fractionation factors are 0.076 ± 0.008 for ISTB-1 and 0.077 ± 0.009 for ZK312-346W. The choice of isotope parameter set had no significant influence on final Δ47 values in this study. However, using the Assonov parameters to calculate Δ47 values improved the reproducibility of the results. The use of carbonate standards improved reproducibility through time compared with the use of equilibrated gases for standardization. CONCLUSIONS: At 90°C, the acid fractionation factors of calcite and dolomite are statistically indistinguishable. We find an insignificant effect from changing the isotope parameter set, suggesting that the choice of isotope parameter set among laboratories is not a major factor affecting inter-laboratory reproducibility. We find that using carbonate standards improved the reproducibility of results, suggesting that the use of carbonate standards may help to achieve inter-laboratory comparability of results in future studies.
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Tandem white organic light-emitting diodes (WOLEDs) are promising for the lighting and displays field since their current efficiency, external quantum efficiency and lifetime can be strikingly enhanced compared with single-unit devices. In this invited review, we have firstly described fundamental concepts of tandem device architectures and their use in WOLEDs. Then, we have summarized the state-of-the-art strategies to achieve high-performance tandem WOLEDs in recent years. Specifically, we have highlighted the developments in the four types of tandem WOLEDs (i.e., tandem fluorescent WOLEDs, tandem phosphorescent WOLEDs, tandem thermally activated delayed fluorescent WOLEDs, and tandem hybrid WOLEDs). Furthermore, we have introduced doping-free tandem WOLEDs. In the end, we have given an outlook for the future development of tandem WOLEDs.
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Luz , Iluminación/instrumentación , Compuestos Orgánicos/química , Color , Complejos de Coordinación/química , Equipos y Suministros Eléctricos , Electrodos , Estructura Molecular , Semiconductores , Relación Estructura-Actividad , TemperaturaRESUMEN
For the first time, compounds with lanthanum from the main family element Boron (LaBx) were investigated as an active layer for thin-film transistors (TFTs). Detailed studies showed that the room-temperature fabricated LaBx thin film was in the crystalline state with a relatively narrow optical band gap of 2.28 eV. The atom ration of La/B was related to the working pressure during the sputtering process and the atom ration of La/B increased with the increase of the working pressure, which will result in the freer electrons in the LaBx thin film. LaBx-TFT without any intentionally annealing steps exhibited a saturation mobility of 0.44 cm²·V−1·s−1, which is a subthreshold swing (SS) of 0.26 V/decade and a Ion/Ioff ratio larger than 104. The room-temperature process is attractive for its compatibility with almost all kinds of flexible substrates and the LaBx semiconductor may be a new choice for the channel materials in TFTs.
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Boro/química , Electrónica , Lantano/química , Temperatura , Cristalografía por Rayos X , Espectroscopía de Fotoelectrones , Espectrofotometría UltravioletaRESUMEN
Prior studies have demonstrated that the mouse hepatitis virus (MHV) A59 strain ns2 protein is a member of the 2H phosphoesterase family and exhibits 2',5'-phosphodiesterase (PDE) activity. During the IFN antiviral response, ns2 cleaves 2',5'-oligoadenylate (2-5A), a key mediator of RNase L activation, thereby subverting the activation of RNase L and evading host innate immunity. However, the mechanism of 2-5A cleavage by ns2 remains unclear. Here, we present the crystal structure of the MHV ns2 PDE domain and demonstrate a PDE fold similar to that of the cellular protein, a kinase anchoring protein 7 central domain (AKAP7(CD)) and rotavirus VP3 carboxy-terminal domain. The structure displays a pair of strictly conserved HxT/Sx motifs and forms a deep, positively charged catalytic groove with ß-sheets and an arginine-containing loop. These findings provide insight into the structural basis for 2-5A binding of MHV ns2.
Asunto(s)
Endorribonucleasas/química , Virus de la Hepatitis Murina/química , Hidrolasas Diéster Fosfóricas/química , Proteínas no Estructurales Virales/química , Proteínas de Anclaje a la Quinasa A/química , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Secuencias de Aminoácidos , Animales , Dominio Catalítico , Clonación Molecular , Secuencia Conservada , Cristalografía por Rayos X , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Virus de la Hepatitis Murina/enzimología , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rotavirus/química , Homología Estructural de Proteína , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismoRESUMEN
Rabies remains a major public health threat around the world. Once symptoms appear, there is no effective treatment to prevent death. In this work, we tested a recombinant parainfluenza virus 5 (PIV5) strain expressing the glycoprotein (G) of rabies (PIV5-G) as a therapy for rabies virus infection: we have found that PIV5-G protected mice as late as 6 days after rabies virus infection. PIV5-G is a promising vaccine for prevention and treatment of rabies virus infection.
Asunto(s)
Vectores Genéticos/genética , Virus de la Parainfluenza 5/genética , Vacunas Antirrábicas/administración & dosificación , Virus de la Rabia/inmunología , Rabia/prevención & control , Proteínas del Envoltorio Viral/administración & dosificación , Animales , Anticuerpos Antivirales/inmunología , Expresión Génica , Vectores Genéticos/metabolismo , Humanos , Ratones , Virus de la Parainfluenza 5/metabolismo , Rabia/inmunología , Rabia/virología , Vacunas Antirrábicas/genética , Vacunas Antirrábicas/inmunología , Virus de la Rabia/genética , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
Deep eutectic solvents (DESs) have emerged as promising alternative candidates for CO2 capture in recent years. In this work, several novel DESs were firstly prepared to enhance CO2 absorption. Structural and physical properties of DESs were investigated, as well as their absorption performance of CO2. A distinct depression in the melting point up to 80 K of DESs was observed compared with that of BMIMCl. The observed red shifts of the C2H group in an imidazolium ring and its chemical shifts downfield in NMR spectra are indicative of a hydrogen bond interaction between BMIMCl and MEA. In particular, CO2 uptake in MEA : ILs (4 : 1) at room temperature and atmospheric pressure is up to 21.4 wt%, which is higher than that of 30 wt% MEA (13%). A hydrogen bond related mechanism was proposed in which ILs act as a medium to improve CO2 uptake through hydrogen bonds. Finally, the firstly reported overall heat of CO2 absorption is slightly higher than that of 30 wt% MEA, implying that the hydrogen bonds of DESs contribute to the overall heat of CO2 absorption. This study reveals that the heat of CO2 absorption can be tailored by the proper molar ratio of MEA and ILs.
RESUMEN
The aim of this study was to examine the microbiological and related parameters (antibiotic resistance and pathogen identification) of water at two salmonid fish farms in Northern Ireland. Total Bacterial Counts at the Movanagher Fish Farm was 1730 colony forming units (cfu)/ml water (log10 3.24cfu/ml) and 3260cfu/ml (log10 3.51cfu/ml) at the Bushmills Salmon Station. Examination of resulting organisms revealed 10 morphological phenotypes, which were subsequently sequenced to determine their identification. All these organisms were Gram-negative and no Gram-positive organisms were isolated from any water sample. From these phenotypes, eight different genera were identified including Acinetobacter, Aeromonas, Chryseobacterium, Erwinia, Flavobacterium, Pseudomonas and Rheinheimera. One unnamed novel taxon was identified from water at the Movanagher Fish Farm, belonging to the genus Acinetobacter and has been tentatively named Acinetobacter movanagherensis. No other novel taxa were observed. All but one of these environmental organisms (Erwinia) are potential pathogens of fish disease. Total antibiotic resistance was observed to varying degrees in water specimens. The most resistant populations were observed in water taken from the Bushmills Salmon Station inlet, followed by water from the Movanagher Fish Farm. No resistance was observed against tetracycline and there was only one occurrence of resistance against ciprofloxacin. Overall, this study indicates that potential fish pathogens made up the majority of environmental organisms identified, even in the absence of recorded fish disease. There was also relatively high levels of total antibiotic resistance in the bacterial water populations examined, where tetracycline was the only antibiotic with zero resistance. These data indicate that the threat of bacterial disease is relatively close due to the indigenous colonization of farm water and that husbandry standards should be maintained at a high standard to avert bacterial disease outbreaks, rather than relying on the absence of specific pathogens in the immediate farm environment.