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The oriented attachment (OA) of nanoparticles (NPs) is an important crystal growth mechanism in many materials. However, a comprehensive understanding of the atomic-scale alignment and attachment processes is still lacking. We conducted in situ atomic resolution studies using high-resolution transmission electron microscopy to reveal how two Pt NPs coalesce into a single particle via OA, which involves the formation of atomic-scale links and a grain boundary (GB) between the NPs, as well as GB migration. Density functional theory calculations showed that the system energy changes as a function of the number of disconnections during the coalescence process. Additionally, the formation and annihilation processes of disconnection are always accompanied by the cooperative reorientation motion of atoms. These results further elucidate the growth mechanism of OA at the atomic scale, providing microscopic insights into OA dynamics and a framework for the development of processing strategies for nanocrystalline materials.
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Prenylation of amino acids is a critical step for synthesizing building blocks of prenylated alkaloid family natural products, where the corresponding prenyltransferase that catalyzes prenylation on free l-histidine (l-His) has not yet been identified. Here, we first discovered and characterized a prenyltransferase FunA from the antifungal agent fungerin pathway that efficiently performs C4-dimethylallylation on l-His. Crystal structure-guided engineering of the prenyl-binding pocket of FunA, a single M181A mutation, successfully converted it into a C4-geranyltransferase. Furthermore, FunA and its variant FunA-M181A show broad substrate promiscuity toward substrates that vary in substituents of the imidazole ring. Our work furthers our knowledge of free amino acid prenyltransferase and expands the arsenal of alkylation biocatalysts for imidazole-containing small molecules.
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OBJECTIVES: Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. METHODS: A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. RESULTS: The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512â mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. CONCLUSIONS: These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.
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A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.
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OBJECTIVE: The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. METHODS: We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. RESULTS: We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P < 0.001; recurrence-free survival , P < 0.001), E (exophytic/endophytic) (overall survival, P = 0.003; recurrence-free survival, P < 0.001), N (nearness) (overall survival, P = 0.063; recurrence-free survival, P < 0.001), A (anterior/posterior) (overall survival, P < 0.001; recurrence-free survival, P = 0.005), L (location) (overall survival, P = 0.008; recurrence-free survival, P < 0.001) and suffix 'h' (overall survival, P = 0.237; recurrence-free survival, P = 0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P < 0.001; recurrence-free survival, P < 0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P = 0.027, hazard ratio (95% confidence interval) = 1.151 (1.016-1.303)] and recurrence-free survival [P < 0.001, hazard ratio (95% confidence interval) = 1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. CONCLUSION: Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.
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Neoplasias Renales , Humanos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Riñón/cirugía , Riñón/patología , Nefrectomía , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the effect of immune checkpoint inhibitors (ICIs) on left ventricular myocardial work by pressure-strain loop (PSL). METHODS: Forty-three immunotherapy patients were enrolled in the case group, and another 43 healthy volunteers were enrolled in the control group. They were examined by echocardiography before immunotherapy (T0 phase), after three cycles of treatment (T3 phase) and after six cycles of treatment (T6 phase). Conventional echocardiographic parameters, left ventricular global longitudinal strain (GLS), and myocardial work indices, including global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), were collected for analysis to compare the results of the different immunotherapy cycles. RESULTS: There were no statistically significant differences of baseline characteristics, conventional echocardiographic parameters, left ventricular strain, and myocardial work indices between T0 phase and control group (all p > .05). There were no statistically significant differences in LVEF between T0, T3, and T6 phase (all p > .05). GLS, GWI, GCW, and GWE were decreased and GWW was increased in T3 and T6 phase. There were no statistically significant difference between GLS in T3 and T0 phase (q = .9057, p > .05). The difference was statistically significant between GLS in T6 and T0 phase (q = 5.5651, p < .01). The difference was statistically significant between GLS in T3 and T6phase(q = 4.6594, p < .01). There were statistically significant difference in GWI, GCW, GWE, and GWW in the T3 and T6 phase compared with the T0 phase (p < .01). CONCLUSION: PSL can effectively evaluate the effect of ICIs on left ventricular myocardial work, to provide a new method for the early clinical detection of ICIs-related cardiotoxicity.
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Cardiotoxicidad , Inhibidores de Puntos de Control Inmunológico , Humanos , Cardiotoxicidad/diagnóstico por imagen , Cardiotoxicidad/etiología , Miocardio , Ecocardiografía , Voluntarios Sanos , Función Ventricular Izquierda , Volumen SistólicoRESUMEN
BACKGROUND: The daily physical activity (PA) patterns of children and adolescents are intricate and ambiguous, with varying effects on myopia resulting from different combinations of PA. This study aims to scrutinize the spectrum of PA patterns among children and adolescents and assess their impact on myopia. METHODS: Data sourced from the 2014 National Student Physical Fitness Survey (Tianjin segment) encompassed PA records and visual acuity measurements of participants. Latent Class Analysis and a generalized linear model were employed to investigate the relationship between PA categories and visual acuity across different educational stages. RESULTS: The study comprised 6465 primary and middle school students, among whom 50.13% were male. PA patterns were categorized into high (27.16%), medium (29.88%) and low visual acuity regulation groups (13.97%) and the nonmainstream group (28.99%). Following adjustments for sex, age, region and BMI, the medium visual acuity regulation group exhibited a lower risk of myopia (OR = 0.617, 95% CI = 0.424-0.897, p = 0.012; OR = 0.654, 95% CI = 0.438-0.976, p = 0.038) compared to the nonmainstream group among junior and senior middle school students. CONCLUSION: The efficacy of diverse PA patterns in mitigating myopia risk varies across educational stages and is influenced by sex-specific factors. It is imperative to advance myopia management strategies by emphasizing tailored PA interventions, discerning between PA patterns and delivering timely guidance and interventions tailored to distinct educational stages and sexes.
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Ejercicio Físico , Análisis de Clases Latentes , Miopía , Agudeza Visual , Humanos , Masculino , Femenino , Niño , Miopía/fisiopatología , Miopía/epidemiología , Ejercicio Físico/fisiología , Adolescente , Agudeza Visual/fisiología , Estudiantes/estadística & datos numéricos , Factores de Riesgo , Estudios TransversalesRESUMEN
OBJECTIVE: To analyze the co-existing patterns of health-related behaviors among children and adolescents at different education stages and the association with obesity. DESIGN: Cross-sectional study. SAMPLE: A total of 5651 primary and secondary school students were drawn from the National Student Physical Health Survey in 2014 with an average age of 13.53 ± 2.87 years. MEASUREMENTS: Physical measurements and questionnaires were completed, which concluded height, weight, and health-related behaviors (sleep, physical activity, dietary, and screen behavior et al.). Latent profile analysis (LPA) was conducted using Mplus 8.3 and SPSS 26.0 was used for other statistical analysis. RESULTS: Three latent classes of health-related behaviors were fitted for each of the education stages. After adjustment for age, gender, and region, the high-screen behavior group were 2.217 (95%CI = 1.030-4.772, p = .042) times more likely to be obesity than the health-behavior group in primary school, and the poor-diet group and poor-diet and high-screen behavior group were 2.101 (95%CI = 1.396-3.396, p < .001) and 1.788 (95%CI = 1.003-3.190, p = .049) times more likely to be overweight than the health-behavior group in junior middle school respectively. CONCLUSION: Obesity is mainly influenced by screen behavior and dietary patterns among children and adolescents. Health-related behavior patterns should be accurately identified and comprehensive joint interventions should be carried out to prevent obesity.
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Conductas Relacionadas con la Salud , Estudiantes , Humanos , Masculino , Femenino , Estudios Transversales , Adolescente , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Niño , Encuestas y Cuestionarios , Obesidad Infantil/epidemiología , Instituciones Académicas , Ejercicio Físico , Encuestas Epidemiológicas , Análisis de Clases LatentesRESUMEN
BACKGROUND: Founder parents play extremely important roles in wheat breeding. Studies into the genetic basis of founder parents and the transmission rules of favorable alleles are of great significance in improving agronomically important traits in wheat. RESULTS: Here, a total of 366 founder parents, widely grown cultivars, and derivatives of four representative founder parents were genotyped based on efficient kompetitive allele-specific PCR (KASP) markers in 87 agronomically important genes controlling yield, quality, adaptability, and stress resistance. Genetic composition analysis of founder parents and widely grown cultivars showed a consistently high frequency of favorable alleles for yield-related genes. This analysis further showed that other alleles favorable for resistance, strong gluten, dwarf size, and early heading date were also subject to selective pressure over time. By comparing the transmission of alleles from four representative founder parents to their derivatives during different breeding periods, it was found that the genetic composition of the representative founder parents was optimized as breeding progressed over time, with the number and types of favorable alleles carried gradually increasing and becoming enriched. There are still a large number of favorable alleles in wheat founder parents that have not been fully utilized in breeding selection. Eighty-seven agronomically important genes were used to construct an enrichment map that shows favorable alleles of four founder parents, providing an important theoretical foundation for future identification of candidate wheat founder parents. CONCLUSIONS: These results reveal the genetic basis of founder parents and allele transmission for 87 agronomically important genes and shed light on breeding strategies for the next generation of elite founder parents in wheat.
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Pan , Triticum , Alelos , Triticum/genética , Fitomejoramiento , GenotipoRESUMEN
Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long-time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron-electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu.
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NAD , Marcadores de Spin , Espectroscopía de Resonancia por Spin del Electrón/métodos , NADP , MaleimidasRESUMEN
BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2 = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Imagen por Resonancia Magnética , Neoplasias de la Próstata , Masculino , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/patología , Inteligencia Artificial , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodosRESUMEN
Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.
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Suspensión Trasera , Mitocondrias Cardíacas , Ratones , Animales , Mitocondrias Cardíacas/metabolismo , Dinámicas Mitocondriales/genética , Proteína X Asociada a bcl-2/metabolismo , Apoptosis/fisiología , Autofagia , Miocitos Cardíacos/metabolismoRESUMEN
We report herein a concise method for the construction of phosphinonyl-azaindoline and -azaoxindole derivatives via a palladium-catalyzed cascade cyclization with P(O)H compounds. Various H-phosphonates, H-phosphinates, and aromatic secondary phosphine oxides are all tolerated under the reaction conditions. Furthermore, the phosphinonyl-azaindoline isomer families such as 7-, 5-, and 4-azaindolines could be synthesized in moderate to good yields.
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Dapagliflozin (DAPA), sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is used to treat Type 2 diabetes. In this study, a highly sensitive and selective analytical method based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was established and validated for the determination of DAPA in rat plasma. The separation of DAPA and internal standard (DAPA-d5) were performed on a reversed-phase ACQUITY UPLC® BEH C18 column (100 × 3.0 mm, 1.7 µm). The mobile phase is composed of 0.1% formic acid in water (solvent A) and methanol (solvent B) in gradient elution. Under the negative ion mode, full MS/dd-MS2 was adopted to collect data via Q-Orbitrap. DAPA was effectively separated from matrix backgrounds within 10 min, and DAPA in plasma showed a good linear relationship in the range of 10-10000 µg/L. The determination coefficient (R2) was 0.9987, and the lower limit of quantification (LLOQ) was 10 µg/L. The precision and accuracy were all less than 10%, and the extraction recovery of DAPA was 86.16-96.06% from plasma. This study offered an efficient separation and quantification method for DAPA. The improved and validated method succeeded in evaluating the pharmacokinetics of DAPA in rat plasma samples after a single oral administration of 1 mg/kg.
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Diabetes Mellitus Tipo 2 , Ratas , Animales , Ratas Sprague-Dawley , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Solventes , Reproducibilidad de los ResultadosRESUMEN
In practical applications, the coalescence of metal nanoparticles (NPs) is a major factor affecting their physical chemistry properties. Currently, due to a lack of understanding of the atomic-level mechanisms during the nucleation and growth stages of coalescence, the correlation between the different dynamic factors in the different stages of NP coalescence is unclear. In this study, we used advanced in situ characterization techniques to observe the formation of atomic material transport channels (Au chains) during the initiation of coalescence nucleation. We focused on the movement and migration states of Au atoms and discovered an atomic ordered arrangement growth mechanism that occurs after the completion of nucleation. Simultaneously, we used density functional theory to reveal the formation principle of Au chains. These findings improve our understanding of the atomic-scale coalescence process, which can provide a new perspective for further research on coalescence atomic dynamics.
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Under climate change, drought is one of the most limiting factors that influences wheat (Triticum aestivum L.) production. Exploring stress-related genes is vital for wheat breeding. To identify genes related to the drought tolerance response, two common wheat cultivars, Zhengmai 366 (ZM366) and Chuanmai 42 (CM42), were selected based on their obvious difference in root length under 15% PEG-6000 treatment. The root length of the ZM366 cultivar was significantly longer than that of CM42. Stress-related genes were identified by RNA-seq in samples treated with 15% PEG-6000 for 7 days. In total, 11,083 differentially expressed genes (DEGs) and numerous single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) were identified. GO enrichment analysis revealed that the upregulated genes were mainly related to the response to water, acidic chemicals, oxygen-containing compounds, inorganic substances, and abiotic stimuli. Among the DEGs, the expression levels of 16 genes in ZM366 were higher than those in CM42 after the 15% PEG-6000 treatment based on RT-qPCR. Furthermore, EMS-induced mutants in Kronos (T. turgidum L.) of 4 representative DEGs possessed longer roots than the WT after the 15% PEG-6000 treatment. Altogether, the drought stress genes identified in this study represent useful gene resources for wheat breeding.
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Sequías , Triticum , Triticum/genética , Triticum/metabolismo , Fitomejoramiento , Perfilación de la Expresión Génica , RNA-Seq , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
OBJECTIVES: To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments. METHODS: ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells. RESULTS: PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 µmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-ß, and protein expression of p-Akt (P<0.05). CONCLUSIONS: PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-ß and activating the PI3K/Akt pathway, and the PDGFR-ß inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.
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Síndrome Mucocutáneo Linfonodular , Trombocitosis , Niño , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Becaplermina , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Trombocitosis/tratamiento farmacológico , Trombocitosis/etiología , ARN MensajeroRESUMEN
OBJECTIVES: To study the clinical and gastroscopic features of children with cyclic vomiting syndrome. METHODS: A retrospective analysis was performed on the medical data of 63 children with cyclic vomiting syndrome who were hospitalized and followed up in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University from August 2019 to March 2022. RESULTS: Among the 63 children, there were 30 boys and 33 girls, with a mean age of 6.11 years, a mean course of disease of 2.57 years, and a mean vomiting period of 4.04 days. The most common accompanying symptom was listlessness or somnolence (55/63, 87%), followed by anorexia (45/63, 71%), abdominal pain or abdominal discomfort (40/63, 63%), constipation (19/63, 30%), salivation (12/63, 19%), nausea (11/63, 17%), headache (11/63, 17%), fever (6/63, 10%), and rash (1/63, 2%). All 63 children underwent gastroscopy, among whom 3 had no marked abnormalities, 22 (35%) had chronic superficial gastritis or chronic non-atrophic gastritis alone, and 38 (60%) had other abnormal changes aside from chronic gastritis (16 children with reflux esophagitis, 12 with bile reflux gastritis, 13 with duodenitis, 10 with erosive gastritis, and 5 with gastric or duodenal ulcer). Among the 63 children, 42 underwent pathological examinations of gastric mucosa, among whom 5 had no marked abnormalities, 34 had mild chronic gastritis, 2 had moderate chronic gastritis, and 1 had severe chronic gastritis. Among the 63 children, 15 received 24-hour dynamic esophageal pH monitoring during the interictal period, among whom 9 children were found to have pathological acid reflux. CONCLUSIONS: In addition to recurrent vomiting, most children with cyclic vomiting syndrome also have the symptoms such as somnolence or listlessness, anorexia, and abdominal pain. The main manifestation on gastroscopy is chronic gastritis, and most children may also have reflux esophagitis, bile reflux gastritis, and erosive gastritis. Mild chronic gastritis is the main pathological change of gastric mucosa.
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Reflujo Biliar , Esofagitis Péptica , Gastritis , Masculino , Femenino , Humanos , Niño , Gastroscopía , Esofagitis Péptica/patología , Reflujo Biliar/patología , Anorexia/patología , Estudios Retrospectivos , Somnolencia , Gastritis/diagnóstico , Gastritis/patología , Mucosa Gástrica/patología , Vómitos/etiología , Vómitos/patología , Dolor AbdominalRESUMEN
As possible alternatives to traditional thermoelectric (TE) materials, carbon nanomaterials and their hybrid materials have great potential in the future application of flexible and lightweight temperature detection. In this work, an integrated, highly flexible, and tailorable TE temperature detector with high performance has been fabricated based on a continuous single-walled carbon nanotube (SWCNT) fiber. The detector consists of more than one pairs of thermocouples composed of p-type SWCNT fiber and n-type SWCNT hybrid fiber in situ doped by polyethylenimine. Due to the node contact mechanism of the detection, the sensitivity of the detector can be improved with the increase of the number of p-n thermocouples, independent of the length of the thermocouple. The temperature detection process of the detector has been studied in detail. In particular, the integrated and flexible detector can be divided into several sub-detectors easily by cutting, illustrating the prospect of large-scale preparation of this kind of novel temperature detectors. Its high flexibility ensures the detector to maintain excellent detection performance after 15 000 bending circles. Furthermore, the as-designed TE type temperature detector demonstrates a great application promise for real-time temperature detection and temperature change sensing even in complex surface and harsh environment.
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Tumour-infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumour-infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 patients with mRCC; TIMs (mast cells density positive to tryptase), along with CD8+ and CD4+ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log-rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression-free survival (OS, P = .008, and PFS, P = .016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR = 0.624, 95% CI: 0.420-0.927, P = .020) and PFS (HR = 0.658, 95% CI: 0.466-0.930, P = .019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one- and two-year OS (P = .002 and P = .004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (P = .008 and P = .001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co-existence of CD8+ and CD4+ TILs, which have anti-tumour effects on activation status.