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High-temperature ultrasonic transducer (HTUT) is essential for non-destructive testing (NDT) in harsh environments. In this paper, a HTUT based on BiScO3-PbTiO3 (BS-PT) piezoelectric ceramics was developed, and the effect of different backing layers on its bandwidth were analyzed. The HTUT demonstrates a broad bandwidth and excellent thermal stability with operation temperature up to 400 °C. By using a 10 mm thick porous alumina backing layer, the HTUT achieves a broad -6 dB bandwidth of 100 %, which is about 4 times superior to the transducer with an air backing layer. The center frequency (fc) of the HTUT remains stable with fluctuations of less than 10 % across the temperature range from room temperature to 400 °C. The HTUT successfully detected simulated defects in pulse-echo mode for NDT over 200 °C. This research not only advances high-temperature ultrasonic transducer technology but also expands the NDT applications in harsh environmental conditions.
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Sphingolipids are a major lipid species found in all eukaryotes. Among structurally complex and diversified lipids, sphingoid bases have been heavily linked to various metabolic diseases. However, most current LC-MS-based methods lack the sensitivity to detect low-abundant sphingoid bases. The 6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization reagent, which efficiently forms covalent bonds with amino groups, has been widely used for amino acid detection. Nevertheless, the commonly used reverse-phase HPLC method for amino acid analysis is not suitable for amphipathic sphingolipids. To address this issue, we report a robust reverse-phase HPLC-MS/MS method capable of separating and detecting hydrophilic amino acids and sphingoid bases in a single run with high sensitivity. This method is also inclusive of other amino metabolites with an expandable target list. We tested this method under various conditions and samples, demonstrating its high reproducibility and sensitivity. Using this approach, we systematically analyzed human serum samples from healthy individuals, dyslipidemia, and type II diabetes mellitus (T2DM) patients, respectively. Two sphingolipids and five amino acids were identified with significant differences between the control and T2DM groups, highlighting the potential of this method in clinical studies.
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PURPOSE: Fibroblast activating protein is a promising target for tumor molecular imaging and therapy. Studies showed that fibroblast activating protein inhibitor (FAPI) radioactive tracers presented superiority over 18F-FDG PET/CT in the evaluation of various cancer types, including pancreatic cancer (PC). Therefore, we conducted this meta-analysis to evaluate and analyze the differences between 68Ga/18F-FAPI and 18F-FDG in PC, in order to provide evidence for the clinical application of FAPI PET imaging. METHODS: In the current meta-analysis, original studies published as of January 1, 2024 were analyzed using radiolabeled FAPI as a diagnostic radioactive tracer and compared to 18F-FDG for PET in PC. Databases searched included pubmed and web of science, and subject headings searched included PC and FAPI. The quality of the enrolled studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies 2, and the meta-analysis was conducted using R language. RESULTS: A total of seven studies including 322 patients compared the diagnostic performance of FAPI PET imaging and 18F-FDG PET/CT in PC. Overall, FAPI PET imaging showed higher pooled sensitivity (0.99 [95% CI: 0.97-1.00] vs. 0.84 [95% CI: 0.70-0.92]) and area under the curve (0.99 [95% CI: 0.98-1.00] vs. 0.91 [95% CI: 0.88-0.93]) than 18F-FDG PET/CT. The evidence showed that FAPI PET imaging is superior to 18F-FDG in pooled sensitivity to primary tumor, lymph node metastasis, and distant metastasis. Moreover, FAPI PET imaging improved TNM staging in 25% of PC patients and changed clinical management in 11.7% of PC patients compared to 18F-FDG. CONCLUSION: FAPI PET imaging is superior to that of 18F-FDG in the detection of primary PC, nodal and distant metastases, TNM staging and clinical management.
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Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.T132A) presented with persistent skin rash featuring hyperkeratosis, parakeratosis and acanthosis, with infiltration of lymphocytes and eosinophils around small blood vessels. In addition, circulating IgE levels and inflammatory cytokines, including IFNα, are found consistently elevated. Transcriptional analysis highlights a type I IFN gene signature in PBMC. Mechanistically, REXO2 (T132A) lacks the ability to cleave RNA and inhibits the activity of wild-type REXO2. This leads to an accumulation of mitochondrial dsRNA in the cytosol, which is recognized by MDA5, leading to the associated type I IFN gene signature. These results demonstrate that in the absence of appropriate regulation by REXO2, aberrant cellular nucleic acids may accumulate and continuously trigger innate sensors, resulting in an inborn error of immunity.
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Heterozigoto , Interferon Tipo I , Helicase IFIH1 Induzida por Interferon , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Helicase IFIH1 Induzida por Interferon/metabolismo , Interferon Tipo I/metabolismo , Interferon Tipo I/genética , Mutação , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/genética , Feminino , Imunidade Inata/genética , Exonucleases/metabolismo , Exonucleases/genética , Células HEK293 , Exorribonucleases/genética , Exorribonucleases/metabolismo , Citosol/metabolismo , RNA de Cadeia Dupla/metabolismo , RNA de Cadeia Dupla/genética , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Genes DominantesRESUMO
Twin births are related with maternal and fetal adverse outcomes. Little was known about the comparability of the cognitive, behavioral development and brain structure between twins and singletons in early adolescence. This retrospective cohort study was based on data from the United States population-based, prospective, longitudinal observational Adolescent Brain Cognitive Development study. Children with complete twin status information were enrolled, and the exposure variable was twin status. Primary outcomes were cognitive, behavioral development and brain structure in early adolescence. Cognitive and behavioral outcomes were assessed by using the NIH Toolbox and Child Behavioral Checklist, respectively. Brain structure was evaluated by the cortical thickness, area, and volume extracted from the magnetic resonance imaging (MRI) data. Subgroup analyses were conducted by prematurity, birth weight, with sibling, genetic profiles, and twin types (zygosity). From 1st September 2016 to 15th November 2018, 11545 children (9477 singletons and 2068 twins) aged 9-10 years were enrolled. Twins showed mildly lower cognitive performance (|t|> 5.104, P-values < 0.001, False Discovery Rate [FDR] < 0.001), better behavioral outcome (|t|> 2.441, P-values < 0.015, FDR < 0.042), such as lower scores for multiple psychiatric disorders and behavioral issues, and smaller cortical volume (t = - 3.854, P-values < 0.001, FDR < 0.001) and cortical area (t = - 3.872, P-values < 0.001, FDR < 0.001). The observed differences still held when stratified for prematurity, birth weight, presence of siblings, genetic profiles, and twin types (zygosity). Furthermore, analyses on the two-year follow-up data showed consistent results with baseline data. Twin status is associated with lower cognitive and better behavioral development in early adolescence accompanied by altered brain structure. Clinicians should be aware of the possible difference when generalizing results from adolescent twin samples to singletons.
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Introduction: Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease. Methods: From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience. Results: The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3. Conclusions: CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.
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BACKGROUND: CircRNA-encoded proteins (CEPs) are emerging as new players in health and disease, and function as baits for the common partners of their cognate linear-spliced RNA encoded proteins (LEPs). However, their prevalence across human tissues and biological roles remain largely unexplored. The placenta is an ideal model for identifying CEPs due to its considerable protein diversity that is required to sustain fetal development during pregnancy. The aim of this study was to evaluate circRNA translation in the human placenta, and the potential roles of the CEPs in placental development and dysfunction. METHODS: Multiomics approaches, including RNA sequencing, ribosome profiling, and LC-MS/MS analysis, were utilised to identify novel translational events of circRNAs in human placentas. Bioinformatics methods and the protein bait hypothesis were employed to evaluate the roles of these newly discovered CEPs in placentation and associated disorders. The pathogenic role of a recently identified CEP circPRKCB119aa in preeclampsia was investigated through qRT-PCR, Western blotting, immunofluorescence imaging and phenotypic analyses. RESULTS: We found that 528 placental circRNAs bound to ribosomes with active translational elongation, and 139 were translated to proteins. The CEPs showed considerable structural homology with their cognate LEPs, but are more stable, hydrophobic and have a lower molecular-weight than the latter, all of which are conducive to their function as baits. On this basis, CEPs are deduced to be closely involved in placental function. Furthermore, we focused on a novel CEP circPRKCB119aa, and illuminated its pathogenic role in preeclampsia; it enhanced trophoblast autophagy by acting as a bait to inhibit phosphorylation of the cognate linear isoform PKCß. CONCLUSIONS: We discovered a hidden circRNA-encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placental development, as well as placental disorders such as preeclampsia. Key points A hidden circRNA-encoded proteome in the human placenta was extensively identified and systematically characterised. The circRNA-encoded proteins (CEPs) are potentially related to placental development and associated disorders. A novel conserved CEP circPRKCB119aa enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear-spliced isoform protein kinase C (PKC) ß in preeclampsia.
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Placenta , Pré-Eclâmpsia , Proteoma , RNA Circular , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Feminino , RNA Circular/genética , RNA Circular/metabolismo , Placenta/metabolismo , Proteoma/metabolismo , Proteoma/genéticaRESUMO
Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.
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Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico , Receptor 7 Toll-Like , Lúpus Eritematoso Sistêmico/genética , Humanos , Animais , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Camundongos , Criança , Feminino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Masculino , Idade de Início , Variação Genética , NF-kappa B/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Adolescente , Células THP-1 , Interferon Tipo I/metabolismoRESUMO
We propose a high-resolution, broad-spectral-range spatial heterodyne Raman spectrometer (SHRS) having separate filters and multi-gratings (SFMG). A prototype of the SFMG-SHRS is built using multi-gratings with four sub-gratings having groove densities of 320, 298, 276, and 254 gr/mm and separate filters with filter bands corresponding to the sub-gratings. We use the SFMG-SHRS to measure the Raman spectra of inorganic and organic compounds with various integration times, laser power, and transparent containers, compare measurements of microplastics with and without the separate filters, and measure mixtures of inorganic powders and organic solutions. The designed SFMG-SHRS makes high-resolution, broad-spectral-range Raman measurements with improved signal-to-noise ratios and visibility of weak Raman peaks even in the presence of fluorescence.
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We propose a spatial heterodyne Raman spectrometer (SHRS) based on a field-widened grating-echelle (FWGE). A normal grating is combined with an echelle grating in a conventional spatial heterodyne spectrometer to eliminate ghost images without using masks, and prevents interference among the spatial frequencies of different diffraction orders. Mathematical expressions and derivation processes are given for the spectral parameters in the FWGE-SHRS and a verification breadboard system is fabricated. The FWGE-SHRS measures Raman spectra of single chemicals and mixed targets with different integration times, laser powers, concentrations, and transparent containers. The results of the experiments demonstrate that the FWGE-SHRS is suitable for high-resolution, broadband Raman measurements for a wide range of applications.
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BACKGROUND: Accurately predicting the hepatocellular carcinoma (HCC) grade may facilitate the rational selection of treatment strategies. The diagnostic efficacy of the combination of Gadolinium ethoxybenzy diethylenetriamine pentaacetic (Gd-EOB-DTPA) enhancement T1 mapping and apparent diffusion coefficient (ADC) values in predicting HCC grade needs further validation. OBJECTIVES: This study aimed to assess the capacity of Gd-EOB-DTPA-enhanced T1 mapping and ADC values, both individually and in combination, to discriminate between different grades of HCC. MATERIALS AND METHODS: From July 2017 to February 2020, 96 patients (male, 83; mean age, 53.67 years; age range, 29-71 years) clinically diagnosed with HCC were included in the present study. All patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI, including T1 mapping sequence) before surgery or biopsy. All the patients were categorized into 3 groups according to the pathological results (including 24 cases of well-differentiated HCCs, 59 cases of moderately differentiated HCCs, 13 cases of and poorly differentiated HCCs). The mean Gd-EOB-DTPA enhanced T1 values (ΔT1=[(T1pre-T1post)/T1pre]×100%) and ADC values between different grading groups of HCC were calculated and compared. The area under the characteristics curve (AUC), the diagnostic threshold, sensitivity, and specificity of ΔT1 and ADC for differential diagnosis were analyzed. RESULTS: Mean ΔT1 was 58% for well-differentiated HCCs, 50% for moderately-differentiated HCCs, and 43% for poorly-differentiated HCCs. ΔT1 showed statistical differences between the groups (P<0.001). The mean ADC values of the 3 groups were 1.11×10-3 mm2/s, 0.91×10-3 mm2/s, and 0.80×10-3mm2/s, respectively. ADC showed statistical differences between the groups (P<0.001). In discriminating well- differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.751 (95% CI: 0.642, 0.859), the AUC of ADC was 0.782 (95% CI: 0.671, 0.894), the AUC of combined model was 0.811 (95% CI: 0.709, 0.914). In discriminating the poorly differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.768 (95% CI: 0.634, 0.902), the AUC of ADC was 0.754 (95% CI: 0.603, 0.904), and the AUC of the combined model was 0.841 (95% CI: 0.729, 0.953). CONCLUSION: Gd-EOB-DTPA enhanced T1 mapping, and ADC values have complementary effects on the sensitivity and specificity for identifying different HCC grades. A combined model of Gd-EOB-DTPA-enhanced MRI T1 mapping and ADC values could improve diagnostic performance for predicting HCC grades.
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Carcinoma Hepatocelular , Meios de Contraste , Gadolínio DTPA , Neoplasias Hepáticas , Gradação de Tumores , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Curva ROCRESUMO
N6-methyladenosine (m6A) is the most abundant modification controlling RNA metabolism and cellular functions, but its roles in placental development are still poorly understood. Here, we characterized the synchronization of m6A modifications and placental functions by mapping the m6A methylome in human placentas (n = 3, each trimester), revealing that the dynamic patterns of m6A were associated with gene expression homeostasis and different biological pathways in placental development. Then, we generated trophoblast-specific knockout mice of Wtap, a critical component of methyltransferase complex, and demonstrated that Wtap was essential for trophoblast proliferation, placentation and perinatal growth. Further in vitro experiments which includes cell viability assays and series molecular binding assays demonstrated that WTAP-m6A-IGF2BP3 axis regulated the RNA stability and translation of Anillin (ANLN) and VEGFA, promoting trophoblast proliferation and secretion. Dysregulation of this regulatory axis was observed in placentas from pregnancies with fetal growth restriction (FGR) or preeclampsia, revealing the pathogenic effects of imbalanced m6A modifications. Therefore, our findings provide novel insights into the functions and regulatory mechanisms of m6A modifications in placental development and placental-related gestational diseases.
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Adenosina , Camundongos Knockout , Placentação , Trofoblastos , Feminino , Adenosina/análogos & derivados , Adenosina/metabolismo , Gravidez , Humanos , Animais , Placentação/genética , Trofoblastos/metabolismo , Trofoblastos/patologia , Camundongos , Placenta/metabolismo , Placenta/patologia , Proliferação de Células , Doenças Placentárias/metabolismo , Doenças Placentárias/patologia , Doenças Placentárias/genética , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/patologia , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fatores de Processamento de RNARESUMO
BACKGROUND: Unhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study. METHODS: Genome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, UK Biobank, and other prominent consortia, with a focus on individuals of European ancestry. The primary analysis utilized an inverse-variance-weighted MR approach supplemented by sensitivity analyses to mitigate potential biases introduced by pleiotropy. Furthermore, a two-step MR framework was employed for mediation analyses. RESULTS: The data analyzed included 200â000-500â000 individuals for each sleep trait, along with approximately 15â000 cases of HDPs. Genetically predicted excessive daytime sleepiness (EDS) exhibited a significant association with an increased risk of HDPs [odds ratio (OR) 2.96, 95% confidence interval (95% CI) 1.40-6.26], and the specific subtype of preeclampsia/eclampsia (OR 2.97, 95% CI 1.06-8.3). Similarly, genetically predicted obstructive sleep apnea (OSA) was associated with a higher risk of HDPs (OR 1.27, 95% CI 1.09-1.47). Sensitivity analysis validated the robustness of these associations. Mediation analysis showed that BMI mediated approximately 25% of the association between EDS and HDPs, while mediating up to approximately 60% of the association between OSA and the outcomes. No statistically significant associations were observed between other genetically predicted sleep traits, such as chronotype, daytime napping, sleep duration, insomnia, snoring, and the risk of HDPs. CONCLUSION: Our findings suggest a causal association between two sleep disorders, EDS and OSA, and the risk of HDPs, with BMI acting as a crucial mediator. EDS and OSA demonstrate promise as potentially preventable risk factors for HDPs, and targeting BMI may represent an alternative treatment strategy to mitigate the adverse impact of sleep disorders.
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Estudo de Associação Genômica Ampla , Hipertensão Induzida pela Gravidez , Análise da Randomização Mendeliana , Humanos , Feminino , Gravidez , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/epidemiologia , Fatores de Risco , Sono/genéticaRESUMO
PURPOSE: To assess the utility of apparent diffusion coefficients (ADCs) of whole tumor volume (WTV) and functional tumor volume (FTV) in determining the pathologicalprognostic factors in epithelial ovarian cancers (EOCs). METHODS: A total of 155 consecutive patients who were diagnosed with EOC between January 2017 and August 2022 and underwent both conventional magnetic resonance imaging and diffusion-weighted imaging were assessed in this study. The maximum, minimum, and mean ADC values of the whole tumor (ADCwmax, ADCwmin, and ADCwmean, respectively) and functional tumor (ADCfmax, ADCfmin, and ADCfmean, respectively) as well as the WTV and FTV were derived from the ADC maps. The univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to assess the correlation between these ADC values and the pathological prognostic factors, namely subtypes, lymph node metastasis (LNM), Ki-67 index, and p53 expression. RESULTS: The ADCfmean value was significantly lower in type II EOC, LNM-positive, and high-Ki-67 index groups compared to the type I EOC, LNM-negative, and low-Ki-67 index groups (p ≤ 0.001). Similarly, the ADCwmean and ADCfmean values were lower in the mutant-p53 group compared to the wild-type-p53 group (p ≤ 0.001). Additionally, the ADCfmean showed the highest area under the ROC curve (AUC) for evaluating type II EOC (0.725), LNM-positive (0.782), and high-Ki-67 index (0.688) samples among the given ROC curves, while both ADCwmean and ADCfmean showed high AUCs for assessing p53 expression (0.694 and 0.678, respectively). CONCLUSION: The FTV-derived ADC values, especially ADCfmean, can be used to assess preoperative prognostic factors in EOCs.
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Carcinoma Epitelial do Ovário , Imagem de Difusão por Ressonância Magnética , Neoplasias Ovarianas , Carga Tumoral , Humanos , Feminino , Imagem de Difusão por Ressonância Magnética/métodos , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Idoso , Adulto , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Metástase Linfática/diagnóstico por imagemRESUMO
Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.
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Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenêmicos , Genoma Viral , Terapia por Fagos , Filogenia , Esgotos , Acinetobacter baumannii/virologia , Acinetobacter baumannii/efeitos dos fármacos , Esgotos/virologia , Esgotos/microbiologia , Animais , Carbapenêmicos/farmacologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Infecções por Acinetobacter/microbiologia , Camundongos , Antibacterianos/farmacologia , Fases de Leitura Aberta , Modelos Animais de Doenças , Mariposas/virologia , Mariposas/microbiologia , Composição de BasesRESUMO
Primary clear cell carcinoma of liver (PCCCL) is a special and relatively rare subtype of hepatocellular carcinoma (HCC), which is more common in people over 50 years of age, with a preference for men and a history of hepatitis B or C and/or cirrhosis. Herein, we present a case of a 60-year-old woman who came to our hospital for medical help with right upper abdominal pain. The imaging examination showed a low-density mass in the right lobe of his liver. In contrast enhanced computed tomography (CT) or T1-weighted imaging, significant enhancement can appear around the tumor during the arterial phase, and over time, the degree of enhancement of the tumor gradually decreases. The lession showed obviously increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/CT. These imaging findings contribute to the diagnosis of PCCCL and differentiate it from other types of liver tumors.
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Phenolic resin (PF) is considered a promising precursor of hard carbon (HC) for advanced-performance anodes in sodium-ion batteries (SIBs) because of its facile designability and high residual carbon yield. However, understanding how the structure of PF precursors influences sodium storage in their derived HC remains a significant challenge. Herein, the microstructure of HC is controlled by the degree of cross-linking of resorcinol-benzaldehyde (RB) resin. We reveal that robust molecular cross-linking in RB resin induced by hydrothermal treatment promotes closed-pore formation in the derived HC. The mechanism is devised for the decomposition of a highly cross-linked RB three-dimensional network into randomly stacked short-range graphitic microcrystals during high-temperature carbonization, contributing to the abundant closed pores in the derived HC. In addition, the high cross-linking degree of RB resin endows its derived HC with a small-sized spherical morphology and large interlayer spacing, which improves the rate performance of HC. Consequently, the optimized hydrothermal treatment HC anode shows a higher specific capacity of 372.7 mAh g-1 and better rate performance than the HC anode without hydrothermal treatment (276.0 mAh g-1). This strategy can provide feasible molecular cross-linking engineering for the development of closed pores in PF-based HC toward enhanced sodium storage.
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BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.
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Cumarínicos , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Estresse Oxidativo , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Linhagem Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Inflamação/tratamento farmacológico , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Identifying environmental determinants of health and clarifying their variations is crucial for health promotion in different cities by providing tailored intervention strategies. Although the association between perceived urban environment and health (e.g., self-rated health) has been repeatedly explored, most studies have focused on cities of a specific size, and it is still unknown whether either significant environment variables or the magnitude of the association would vary across different-sized cities. This study investigated how perceived urban environment variables significantly associated with individuals' self-rated health varied from small cities to mega cities in China, based on a national survey including 5963 valid respondents. The results showed that the relationship between self-rated health and city size was U-shaped, with respondents in medium and large cities reporting a low-level self-rated health. Perceived greenness, public facilities, housing supply, and medical services were positively and significantly associated with self-rated health, with the odds ratio (OR) of 1.37 (95%CI: 1.29-1.46), 1.27 (95%CI: 1.19-1.35), 1.14 (95%CI: 1.09-1.20), and 1.17 (95%CI: 1.10-1.24), respectively. Furthermore, the magnitude of the association was significantly larger in mega cities. These findings provide useful evidence for promoting public health in cities of different sizes for achieving health equity and indicate that smaller cities and their health-supportive environment need further attention.
Assuntos
Cidades , Humanos , China , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Autorrelato , Percepção , Nível de Saúde , Idoso , Inquéritos e Questionários , AdolescenteRESUMO
Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.