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OBJECTIVE: The present study aimed to develop the utility of a nomogram based on clinical and radiomics as a tool for predicting post-acute pancreatitis diabetes mellitus (PPDM-A). METHODS: This retrospective investigation evaluated 244 patients with acute pancreatitis (AP). Patients were randomized in a 7:3 ratio into training and validation cohorts. Radiomics feature selection was then achieved using the variance threshold, select best K, and least absolute shrinkage and selection operator (LASSO) methods. The area under the curve (AUC) values, decision, and calibration curves have been used to determine the models' predictive value. RESULTS: The developed nomogram performed superior to the clinical model in the validation (0.815 vs 0.677, p = 0.016) and training groups (0.803 vs 0.683, p = 0.002). The calibration curves demonstrated that the expected and actual values were satisfactory. In contrast, decision curve analysis revealed a stronger relationship between the nomogram and net clinical value than with the distinct radiomics or clinical signature effects. CONCLUSIONS: In summary, the findings of this study demonstrated that establishing a predictive nomogram as a non-invasive technique may be useful in predicting the risk of PPDM-A. ADVANCES IN KNOWLEDGE: This is the first time to use a CT radiomics nomogram to predict PPDM-A. The nomogram is conducive to the personalized prediction of patients. It only needs to input the patient's information, and a simple addition operation can quantitatively obtain its risk. The resultant tool has the potential to provide new opportunities to treat or prevent PPDM-A more effectively.
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Cultivated peanut (Arachis hypogaea L.) is an important economic and oilseed crop worldwide, providing high-quality edible oil and high protein content. Seed size/weight and oil content are two important determinants of yield and quality in peanut breeding. To identify key regulators controlling these two traits, two peanut cultivars with contrasting phenotypes were compared to each other, one having a larger seed size and higher oil content (Zhonghua16, ZH16 for short), while the second cultivar had smaller-sized seeds and lower oil content (Zhonghua6, ZH6). Whole transcriptome analyses were performed on these two cultivars at four stages of seed development. The results showed that ~40% of the expressed genes were stage-specific in each cultivar during seed development, especially at the early stage of development. In addition, we identified a total of 5356 differentially expressed genes (DEGs) between ZH16 and ZH6 across four development stages. Weighted gene co-expression network analysis (WGCNA) based on DEGs revealed multiple hub genes with potential roles in seed size/weight and/or oil content. These hub genes were mainly involved in transcription factors (TFs), phytohormones, the ubiquitin-proteasome pathway, and fatty acid synthesis. Overall, the candidate genes and co-expression networks detected in this study could be a valuable resource for genetic breeding to improve seed yield and quality traits in peanut.
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Introduction: Congenital or acquired bone defects in the oral and cranio-maxillofacial (OCMF) regions can seriously affect the normal function and facial appearance of patients, and cause great harm to their physical and mental health. To achieve good bone defect repair results, the prosthesis requires good osteogenic ability, appropriate porosity, and precise three-dimensional shape. Tantalum (Ta) has better mechanical properties, osteogenic ability, and microstructure compared to Ti6Al4V, and has become a potential alternative material for bone repair. The bones in the OCMF region have unique shapes, and 3D printing technology is the preferred method for manufacturing personalized prosthesis with complex shapes and structures. The surface characteristics of materials, such as surface morphology, can affect the biological behavior of cells. Among them, nano-topographic surface modification can endow materials with unique surface properties such as wettability and large surface area, enhancing the adhesion of osteoblasts and thereby enhancing their osteogenic ability. Methods: This study used 3D-printed porous tantalum scaffolds, and constructed nano-topographic surface through hydrothermal treatment. Its osteogenic ability was verified through a series of in vitro and in vivo experiments. Results: The porous tantalum modified by nano-topographic surface can promote the proliferation and osteogenic differentiation of BMSCs, and accelerate the formation of new bone in the Angle of the mandible bone defect of rabbits. Discussion: It can be seen that 3D-printed nano-topographic surface modified porous tantalum has broad application prospects in the repair of OCMF bone defects.
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BACKGROUND: anti-Programmed Death-1 (anti-PD-1) immunotherapy has shown promising manifestation in improving the survival rate of patients with advanced melanoma, with its efficacy closely linked to Programmed cell death-Ligand 1 (PD-L1) expression. However, low clinical efficacy and drug resistance remain major challenges. Although the metabolic alterations from tricarboxylic acid (TCA) cycle to glycolysis is a hallmark in cancer cells, accumulating evidence demonstrating TCA cycle plays critical roles in both tumorigenesis and treatment. METHODS: The plasma levels of metabolites in patients with melanoma were measured by nuclear magnetic resonance (NMR) spectroscopy. The effect of pyruvate dehydrogenase subunit 1 (PDHA1) and oxoglutarate dehydrogenase (OGDH) on immunotherapy was performed by B16F10 tumor-bearing mice. Flow cytometry analyzed the immune microenvironment. RNA sequencing analyzed the global transcriptome alterations in CPI613-treated melanoma cells. The regulation of PD-L1 and glycolysis by PDHA1/OGDH-ATF3 signaling were confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, dual-luciferase reporter gene, Chromatin immunoprecipitation (ChIP)-quantitative PCR and Seahorse assay. The relationship between PDHA1/OGDH-ATF3-glycolysis and the efficacy of melanoma anti-PD-1 immunotherapy was verified in the clinical database and single-cell RNA-seq (ScRNA-Seq). RESULTS: In our study, the results showed that significant alterations in metabolites associated with glycolysis and the TCA cycle in plasma of patients with melanoma through NMR technique, and then, PDHA1 and OGDH, key enzymes for regulation TCA cycle, were remarkable raised in melanoma and negatively related to anti-PD-1 efficacy through clinical database analysis as well as ScRNA-Seq. Inhibition of PDHA1 and OGDH by either shRNA or pharmacological inhibitor by CPI613 dramatically attenuated melanoma progression as well as improved the therapeutic efficacy of anti-PD-1 against melanoma. Most importantly, suppression of TCA cycle remarkably raises PD-L1 expression and glycolysis flux through AMPK-CREB-ATF3 signaling. CONCLUSIONS: Taken together, our results demonstrated the role of TCA cycle in immune checkpoint blockade and provided a novel combination strategy for anti-PD-1 immunotherapy in melanoma treatment.
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Antígeno B7-H1 , Melanoma , Animais , Camundongos , Imunoterapia , Caprilatos , Melanoma/tratamento farmacológico , Microambiente TumoralRESUMO
Solar and wind resources are vital for the sustainable energy transition. Although renewable potentials have been widely assessed in existing literature, few studies have examined the statistical characteristics of the inherent renewable uncertainties arising from natural randomness, which is inevitable in stochastic-aware research and applications. Here we develop a rule-of-thumb statistical learning model for wind and solar power prediction and generate a year-long dataset of hourly prediction errors of 30 provinces in China. We reveal diversified spatiotemporal distribution patterns of prediction errors, indicating that over 60% of wind prediction errors and 50% of solar prediction errors arise from scenarios with high utilization rates. The first-order difference and peak ratio of generation series are two primary indicators explaining the uncertainty distribution. Additionally, we analyze the seasonal distributions of the provincial prediction errors that reveal a consistent law in China. Finally, policies including incentive improvements and interprovincial scheduling are suggested.
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Background: Young children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children. Methods: The influenza vaccination records for all children born during 2013-2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses. Results: During the study period, the annual vaccination coverage rate ranged from 10.40% in 2013-2014 to 27.62% in 2015-2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23-0.34) during 2013-2014 (PF: 6.15%, range: 5.11-7.38%) to a high of 15.34 (range: 12.38-18.51) during 2017-2018 (PF: 16.54%, range: 13.79-19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27-10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2-5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses. Conclusion: Influenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.
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Influenza Humana , Humanos , Criança , Pré-Escolar , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vacinação , Cobertura Vacinal , China/epidemiologia , Efeitos Psicossociais da DoençaRESUMO
Background: Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. Materials and Methods: Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. Results: Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. Conclusions: The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Tireoidite , Humanos , Dipeptidil Peptidase 4/genética , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
Introduction: Language media from one's hometown is an important means of maintaining cultural identification, especially for minorities. Cantonese media plays an active role in shaping the Chinese cultural identification of ethnic Chinese all over the world. To date, few researchers have undertaken quantitative empirical analyses of the mechanism through which Cantonese media influences cultural identification. Methods: Using data from 642 Malaysian Chinese, this study established a structural equation model with the partial least squares method. Results: We found that the emotional affinity of ethnic Chinese to Cantonese media can influence identification with Chinese culture through the perceived value of Cantonese media and cognition of Chinese culture. The perceived value of Cantonese media (IE = 0.208) and cognition of Chinese culture (IE = 0.068) play partial mediation roles. Meanwhile, emotional affinity to Cantonese media influences cognition of Chinese culture (IE = 0.069) through the chain mediation of perceived value of Cantonese media and cognition of Chinese culture. Age has a partial moderating effect in the structural equation model. Compared with minors, adults' emotional affinity to Cantonese media can eventually influence identification with Chinese culture (TEdiff = 0.126) more strongly through several mediation paths. Discussion: The study suggests a need to cultivate the emotional affinity of ethnic Chinese to Cantonese media, improve the multidimensional values of Cantonese media, and endow Cantonese media with functions of cultural dialog and knowledge transmission. The international transmission of Cantonese media could play a vital role in building a cultural community for ethnic Chinese globally.
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INTRODUCTION: Peanut is susceptible to infection of Aspergillus fungi and conducive to aflatoxin contamination, hence developing aflatoxin-resistant variety is highly meaningful. Identifying functional genes or loci conferring aflatoxin resistance and molecular diagnostic marker are crucial for peanut breeding. OBJECTIVES: This work aims to (1) identify candidate gene for aflatoxin production resistance, (2) reveal the related resistance mechanism, and (3) develop diagnostic marker for resistance breeding program. METHODS: Resistance to aflatoxin production in a recombined inbred line (RIL) population derived from a high-yielding variety Xuhua13 crossed with an aflatoxin-resistant genotype Zhonghua 6 was evaluated under artificial inoculation for three consecutive years. Both genetic linkage analysis and QTL-seq were conducted for QTL mapping. The candidate gene was further fine-mapped using a secondary segregation mapping population and validated by transgenic experiments. RNA-Seq analysis among resistant and susceptible RILs was used to reveal the resistance pathway for the candidate genes. RESULTS: The major effect QTL qAFTRA07.1 for aflatoxin production resistance was mapped to a 1.98 Mbp interval. A gene, AhAftr1 (Arachis hypogaea Aflatoxin resistance 1), was detected structure variation (SV) in leucine rich repeat (LRR) domain of its production, and involved in disease resistance response through the effector-triggered immunity (ETI) pathway. Transgenic plants with overexpression of AhAftr1(ZH6) exhibited 57.3% aflatoxin reduction compared to that of AhAftr1(XH13). A molecular diagnostic marker AFTR.Del.A07 was developed based on the SV. Thirty-six lines, with aflatoxin content decrease by over 77.67% compared to the susceptible control Zhonghua12 (ZH12), were identified from a panel of peanut germplasm accessions and breeding lines through using AFTR.Del.A07. CONCLUSION: Our findings would provide insights of aflatoxin production resistance mechanisms and laid meaningful foundation for further breeding programs.
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The lignin plays one of the most important roles in plant secondary metabolism. However, it is still unclear how lignin can contribute to the impressive height of wood growth. In this study, C3'H, a rate-limiting enzyme of the lignin pathway, was used as the target gene. C3'H3 was knocked out by CRISPR/Cas9 in Populus tomentosa. Compared with wild-type popular trees, c3'h3 mutants exhibited dwarf phenotypes, collapsed xylem vessels, weakened phloem thickening, decreased hydraulic conductivity and photosynthetic efficiency, and reduced auxin content, except for reduced total lignin content and significantly increased H-subunit lignin. In the c3'h3 mutant, the flavonoid biosynthesis genes CHS, CHI, F3H, DFR, ANR, and LAR were upregulated, and flavonoid metabolite accumulations were detected, indicating that decreasing the lignin biosynthesis pathway enhanced flavonoid metabolic flux. Furthermore, flavonoid metabolites, such as naringenin and hesperetin, were largely increased, while higher hesperetin content suppressed plant cell division. Thus, studying the c3'h3 mutant allows us to deduce that lignin deficiency suppresses tree growth and leads to the dwarf phenotype due to collapsed xylem and thickened phloem, limiting material exchanges and transport.
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Serine/threonine protein kinase PLK4 is a master regulator of centriole duplication, which is significant for maintaining genome integrity. Accordingly, due to the detection of PLK4 overexpression in a variety of cancers, PLK4 has been identified as a candidate anticancer target. Thus, it is a very meaningful to find effective and safe PLK4 inhibitors for the treatment of cancer. However, the reported PLK4 inhibitors are scarce and have potential safety issues. In this study, a series of novel and potent PLK4 inhibitors with an aminopyrimidine core was obtained utilizing the scaffold hopping strategy. The in vitro enzyme activity results showed that compound 8h (PLK4 IC50 = 0.0067 µM) displayed high PLK4 inhibitory activity. In addition, compound 8h exhibited a good plasma stability (t1/2 > 289.1 min), liver microsomal stability (t1/2 > 145 min), and low risk of DDIs. At the cellular level, it presented excellent antiproliferative activity against breast cancer cells. Taken together, these results suggest that compound 8h has potential value in the further research of PLK4-targeted anticancer drugs.
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BACKGROUND: Cancer has become significant comorbidity in patients with atrial fibrillation (AF). However, little is known about the efficacy and safety of AF ablation, the first-line rhythm control strategy, in patients with cancer. This study aims to evaluate the incidence and risk of AF recurrence and safety endpoints in patients with cancer compared to the non-cancer group after ablation. METHODS: From August 2011 to December 2020, we consecutively enrolled cancer patients in the China-AF cohort. We used propensity score matching (1:3) to select the control group and assessed the risk of AF recurrence and adverse events after ablation in cancer patients using a multivariable Fine and Gray competing risk model. RESULTS: A total of 203 patients with cancer were enrolled and 21 of them were active cancer, with a median follow-up of 12.3 months. The cumulative incidence of AF recurrence was comparable between patients with and without cancer (43.8% vs. 51.1%; p = .88). No difference in the risk of AF recurrence, thromboembolism, major bleeding, and mortality was observed after adjusting confounders. Active cancer was not associated with an increased risk of AF recurrence compared to the stable disease (SHR = 1.32; 95% CI 0.72-2.43; p = .46). Cancer was associated with a low risk of cardiovascular hospitalization (SHR, 0.54; 95% CI, 0.36-0.81; p = .01). Subgroup analysis found that hematological malignancy was associated with a high risk of AF recurrence (SHR, 5.68; 95% CI, 3.00-10.8; p < .001). CONCLUSIONS: This study suggests that catheter ablation could be feasible for rhythm control of AF patients with concomitant cancer.
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Background The knowledge gap regarding whether the correlation between atrial fibrillation (AF) and dementia in observational studies is causation or driven by other shared risk factors remains substantially unfilled. Methods and Results We performed a comprehensive 2-sample Mendelian randomization study to evaluate the causal effect of AF on overall dementia and its subtypes, including vascular dementia, Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. The primary results in inverse variance-weighted analyses were further validated by various Mendelian randomization sensitivity analyses. Additionally, we conducted multivariable Mendelian randomization to examine 10 candidate mediators of the causal association of AF and dementia. Genetic predisposition to AF was modestly associated with an increased risk of overall dementia (odds ratio, 1.140 [95% CI, 1.023-1.271]; P=0.018) and strongly associated with vascular dementia (odds ratio, 1.350 [95% CI, 1.076-1.695]; P=0.010). Genetically predicted AF indicated neutral effects on Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. In multivariable Mendelian randomization analysis, the total effect of AF on overall dementia was remarkably attenuated by adjusting for genetic effect for ischemic stroke (odds ratio, 1.068 [95% CI, 0.953-1.197]; P=0.259) and low cardiac output (odds ratio, 1.046 [95% CI, 0.926-1.181]; P=0.475), indicating that the causal association of genetically predicted AF with dementia was potentially mediated by ischemic stroke and low cardiac output. The causal effect of genetically predicted AF on dementia was independent of cerebral small-vessel disease and brain volume phenotypes. Conclusions Our findings provided novel evidence supporting the causal effect of genetically predicted AF on dementia mediated by ischemic stroke and low cardiac output. Future clinical trials are warranted to evaluate the potential role of appropriate AF management in dementia prevention.
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Doença de Alzheimer , Fibrilação Atrial , Demência Vascular , Demência Frontotemporal , AVC Isquêmico , Doença por Corpos de Lewy , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Doença de Alzheimer/genética , Demência Vascular/diagnóstico , Demência Vascular/epidemiologia , Demência Vascular/genética , Doença por Corpos de Lewy/complicações , Análise da Randomização Mendeliana , Demência Frontotemporal/complicações , Baixo Débito Cardíaco/complicações , AVC Isquêmico/complicações , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla/métodosRESUMO
The versatility of cellular metabolism in converting various substrates to products inspires sustainable alternatives to conventional chemical processes. Metabolism can be engineered to maximize the yield, rate, and titer of product generation. However, the numerous combinations of substrate, product, and organism make metabolic engineering projects difficult to navigate. A perfect trifecta of substrate, product, and organism is prerequisite for an environmentally and economically sustainable metabolic engineering endeavor. As a step toward this endeavor, we propose a reverse engineering strategy that starts with product selection, followed by substrate and organism pairing. While a large bioproduct space has been explored, the top-ten compounds have been synthesized mainly using glucose and model organisms. Unconventional feedstocks (e.g. hemicellulosic sugars and CO2) and non-model organisms are increasingly gaining traction for advanced bioproduct synthesis due to their specialized metabolic modes. Judicious selection of the substrate-organism-product combination will illuminate the untapped territory of sustainable metabolic engineering.
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Engenharia Metabólica , Açúcares , Glucose/metabolismoRESUMO
In animal studies, sodium-glucose co-transporter-2 inhibitors-such as empagliflozin-have been shown to improve heart failure and impaired cardiac contractility induced by anthracyclines-including doxorubicin-although the therapeutic mechanism remains unclear. Moreover, abnormalities in Ca2+ handling within ventricular myocytes are the predominant feature of heart failure. Accordingly, this study aimed to investigate whether empagliflozin can alleviate Ca2+ handling disorders induced by acute doxorubicin exposure and elucidate the underlying mechanisms. To this end, ventricular myocytes were isolated from C57BL/6 mice. Contraction function, Ca2+ handling, and mitochondrial reactive oxygen species (ROS) generation were then evaluated using IonOptix or confocal microscopy. Ca2+ handling proteins were detected by western blotting. Results show that incubation with 1 µmol/L of doxorubicin for 120-min impaired cardiac contractility in isolated myocytes, which was significantly alleviated by pretreatment with 1 µmol/L of empagliflozin. Doxorubicin also markedly induced Ca2+ handling disorders, including decreased Ca2+ transients, prolonged Ca2+ transient decay time, enhanced frequency of Ca2+ sparks, and decreased Ca2+ content in the sarcoplasmic reticulum. These dysregulations were improved by pretreatment with empagliflozin. Moreover, empagliflozin effectively inhibited doxorubicin-induced mitochondrial ROS production in isolated myocytes and rescued doxorubicin-induced oxidation of Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) and CaMKII-dependent phosphorylation of RyR2. Similarly, preincubation with 10 µmol/L Mito-TEMPO mimicked the protective effects of empagliflozin. Collectively, Empagliflozin ameliorated the doxorubicin-induced contraction malfunction and Ca2+-handling disorders. These findings suggest that empagliflozin alleviates Ca2+-handling disorders by improving ROS production in the mitochondria and alleviating the enhanced oxidative CaMKII signaling pathway induced by doxorubicin.
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BACKGROUND: Systolic blood pressure (SBP) time in target range (TTR) indicates the mean value, exposure time, and variability in blood pressure over time. The prognostic value of SBP TTR for incident atrial fibrillation (AF) in patients with hypertension is unclear. METHODS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. SBP target ranges for intensive and standard arms were defined as 110 to 130 and 120 to 140 mm Hg, respectively. TTR was calculated by linear interpolation method using SBP from months 0 to 3. We used Cox proportional regression models to assess the association of SBP TTR with incident AF. RESULTS: Among 7939 participants included in this analysis, 187 incident AF cases occurred during follow-up. After multivariable adjustment, a 10% increase in SBP TTR was independently associated with a 7% lower risk of incident AF (hazard ratio, 0.93 [95% CI, 0.88-0.97]; P=0.003). The restricted spline curve depicted a linear and inverse relationship between SBP TTR and incident AF. Sensitivity analyses generated consistent results when calculating TTR over a longer period or setting target range as 110 to 140 mm Hg for the whole population. CONCLUSIONS: Higher SBP TTR independently predicts a lower risk of incident AF. Efforts to attain SBP within 110 to 140 mm Hg over time may be an effective strategy to prevent AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.
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Rationale and objectives: To investigate the predictive value of lipid metabolism in predicting the recurrence of hypertriglyceridemic acute pancreatitis (HTG-AP). Materials and methods: A total of 892 patients were admitted to our hospital for acute pancreatitis (AP) from January 2017 to December 2020, of whom 198 diagnosed with HTG-AP were enrolled in this retrospective study. Demographic information, length of stay, smoking index, alcohol abuse, necrosis, severity, baseline lipid metabolism and other blood biochemical indicators were recorded. The risk factors of recurrence were evaluated using univariate and multivariate Cox proportional risk analyses, and the cumulative recurrence-free survival rate of patients were calculated using Kaplan Meier method and the differences between groups were compared using the log-rank test. Results: Univariate and multivariate analysis showed that triglyceride (hazard ratio, 2.421; 95% CI, 1.152-5.076; P = 0.020), non high-density lipoprotein (hazard ratio, 4.630; 95% CI, 1.692-12.658; P = 0.003) and apolipoprotein A1 (hazard ratio, 1.735; 95% CI, 1.093-2.754; P = 0.019) were important predictors for recurrence of HTG-AP. Subsequently, patients were divided into four groups according to the cut off values of triglyceride, non high-density lipoprotein and apolipoprotein A1. It was found that the cumulative recurrence-free survival rate of patients in highest-risk group or high-risk group was significantly lower than that of medium-risk group (P < 0.001, P = 0.003) or low risk group (P < 0.001). Conclusion: Serum triglycerides, non high-density lipoprotein and apolipoprotein A1 are independent predictors of recurrence in HTG-AP patients, which can provide reference for individualized treatment and prevention of recurrence in HTG-AP patients.
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Since the exosomal protein level is related to many diseases, sensitive detection of exosomal protein is highly desirable. Here, we describe a polymer-sorted high-purity semiconducting carbon nanotubes (CNTs) films-based field-effect transistor (FET) biosensor for ultrasensitive and label-free detection of MUC1, a transmembrane protein highly expressed in breast cancer exosomes. Polymer-sorted semiconducting CNTs hold advantages including high purity (>99%), high CNT concentration, and short processing time (<1 h), but they are difficult to be stably functionalized with biomolecules because of lacking hanging bonds on their surface. To solve this issue, poly-lysine (PLL) was employed to modify the CNT films after they were deposited on the sensing channel surface of the fabricated FET chip. To specifically recognize the exosomal protein, sulfhydryl aptamer probes were immobilized on the gold nanoparticles (AuNPs) surface that was assembled on PLL substrate. The aptamer-modified CNT FET was capable of sensitively and selectively detecting exosomal MUC1 as high as 0.34 fg/mL. Moreover, the CNT FET biosensor was able to recognize breast cancer patients from healthy individuals by comparing the expression level of exosomal MUC1. The developed CNT FET biosensor is expected to be a novel assay for early diagnosis of cancer.
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Técnicas Biossensoriais , Neoplasias da Mama , Nanopartículas Metálicas , Nanotubos de Carbono , Humanos , Feminino , Ouro/química , Nanotubos de Carbono/química , Nanopartículas Metálicas/química , Proteínas , Neoplasias da Mama/diagnósticoRESUMO
Purpose: To evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment. Method: 64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model's performance. A nomograph was constructed to visualize the model. Results: The D value of the sufficient ablation group (931.0(851.5-987.4) × 10-6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10-6 mm2/s) (p<0.001). However, differences in D*, f, and rBF values between the groups were not significant (p>0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance. Conclusion: The IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.
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Dihydroflavonol 4-reductase (DFR) is a key enzyme in the flavonoid biosynthetic pathway and is essential for the formation of plants' color. In this study, 26 BnDFR genes were identified using 6 Arabidopsis DFR genes as reference. The physicochemical properties, subcellular localization, and conserved structure of BnDFR proteins were analyzed; the evolutionary relationship, collinearity analysis, and expression characteristics of BnDFR genes were studied; and the correlation between the expression level of BnDFR genes and anthocyanin content in rape petals were analyzed. The results showed that the 26 BnDFRs were located in chloroplasts, cytoplasm, nuclei, and mitochondria, distributed on 17 chromosomes, and divided into 4 groups; members of the same group have a similar function, which may be related to the environmental response elements and plant hormone response elements. Intraspecific collinearity analysis showed 51 pairs of collinear genes, and interspecific collinearity analysis showed 30 pairs of collinear genes. Analysis of the expression levels of BnDFRs and anthocyanin content in different color rape petals showed that BnDFR6 and BnDFR26 might play an important role in the synthesis of anthocyanins in rape petals. This provides theoretical guidance for further analysis of the anthocyanin anabolism mechanism involved in the DFR gene in Brassica napus.