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In this study, two types of microgel particles from egg yolk components were prepared by combining enzymatic hydrolysis with high-pressure homogenization (HPH), and their differences in physicochemical properties, foaming properties, and microstructure were compared. Results showed that the particle size of both types of microgel particles had decreased from 2744.07⯱â¯408.26â¯nm (egg yolk, EY) to 144.97⯱â¯3.19â¯nm (PLA2 hydrolyzed egg yolk microgel particles, PYM) and 535.07⯱â¯46.07â¯nm (egg yolk microgel particles hydrolyzed by PLA2, YMP), from 736.24⯱â¯34.61â¯nm (EG) to 182.76⯱â¯4.12â¯nm (PLA2 hydrolyzed egg yolk granules microgel particles, PGM) and 443.98⯱â¯27.09â¯nm (egg yolk granules microgel particles hydrolyzed by PLA2, GMP). Besides, their interfacial adsorption abilities were significantly improved, reflected in the increase values in overrun, from161.90â¯%⯱â¯9.84â¯% (EY) to 269.64â¯%⯱â¯16.73â¯% (PMY) and 307.20â¯%⯱â¯16.09â¯% (YMP), from 189.21â¯%⯱â¯5.02â¯% (EG) to 280.38â¯%⯱â¯36.05â¯% (PGM) and 261.91â¯%⯱â¯34.03â¯% (GMP). Their structural properties showed higher stabilities after treatments. When the microgel particles are applied to cakes, the specific volume was increased from 2.05⯱â¯0.1â¯mL/g (EY) to 2.25⯱â¯0.13â¯mL/g (PYM) and 2.45⯱â¯0.03â¯mL/g (YPM), and from 2.00⯱â¯0.09â¯mL/g (EG) to 2.51⯱â¯0.13â¯mL/g (PGM) and 2.75⯱â¯0.21â¯mL/g (GMP), respectively. The hardness and chewiness were reduced with both types of microgel particles from egg yolk components, which indicated their potential value as edible foam stabilizers in the baking industry.
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BACKGROUND: The significant expression of PD-L1 in thymic epithelial tumors (TETs) has been confirmed, and immunotherapy and its combination therapy have been effective in TETs. However, there is no present evidence that the expression levels of PD-L1 affects the efficacy of combination therapy. Our study aimed to shed light on this relationship. METHODS: Patients with thymic epithelial tumors (TETs) from multicenter hospitals were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) in 22 patients were included. We divided the patients the 22 patients with PD-L1 test into three levels (high expression, low expression and no expression) and analyzed the relationship between the levels of PD-L1 expression and the efficacy of combination therapy. RESULTS: Combination therapy showed an effective benefit in 22 patients with TETs, the median PFS (mPFS) was 16 months (95% CI: 8.5-23.5) and the median OS (mOS) was 38 months (95% CI: 21.5-54.5). Cox-regressive analysis found whether PD-L1 expression affected the PFS of patients (p = 0.017). Among the patients with PD-L1 expression, the levels of expression were correlated with curative effect (Kruskal-Wallis test, PFS: P = 0.012; OS: P = 0.01), and high expression group was along with better efficacy than low expression (Wilcoxon test, P = 0.01). Moreover, in 17 patients treated with immunotherapy combined with chemotherapy, the expression of PD-L1 was also associated with efficacy (Kruskal-Wallis test, p = 0.021). CONCLUSIONS: PD-L1 expression affects the PFS of patients. High expression of PD-L1 patients with TETs responded better to combination therapy, which could provide a therapeutic option in clinic. Besides, other targeted treatments should be considered.
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Tissue stiffening is a predominant feature of fibrotic disorders, but the response of macrophages to changes in tissue stiffness and cellular context in fibrotic diseases remains unclear. Here, we found that the mechanosensitive ion channel Piezo1 was up-regulated in hepatic fibrosis. Macrophages lacking Piezo1 showed sustained inflammation and impaired spontaneous resolution of early liver fibrosis. Further analysis revealed an impairment of clearance of apoptotic cells by macrophages in the fibrotic liver. Macrophages showed enhanced efferocytosis when cultured on rigid substrates but not soft ones, suggesting stiffness-dependent efferocytosis of macrophages required Piezo1 activation. Besides, Piezo1 was involved in the efficient acidification of the engulfed cargo in the phagolysosomes and affected the subsequent expression of anti-inflammation genes after efferocytosis. Pharmacological activation of Piezo1 increased the efferocytosis capacity of macrophages and accelerated the resolution of inflammation and fibrosis. Our study supports the antifibrotic role of Piezo1-mediated mechanical sensation in liver fibrosis, suggesting that targeting PIEZO1 to enhance macrophage efferocytosis could induce fibrosis regression.
Subject(s)
Ion Channels , Liver Cirrhosis , Macrophages , Phagocytosis , Ion Channels/metabolism , Ion Channels/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/genetics , Animals , Macrophages/metabolism , Mice , Humans , Apoptosis , Mice, Inbred C57BL , Disease Models, Animal , EfferocytosisABSTRACT
The component analysis of raw meal is critical to the quality of cement. In recent years, near-infrared (NIR) has been emerged as an innovative and efficient analytical method to determine the oxide content of cement raw meal. This study aims to utilize NIR spectroscopy combined with machine learning and chemometrics to improve the prediction of oxide content in cement raw meal. The Savitzky-Golay convolution smoothing method is applied to eliminate noise interference for the analysis of calcium carbonate ( C a C O 3 ), silicon dioxide ( S i O 2 ), aluminum oxide ( A l 2 O 3 ), and ferric oxide ( F e 2 O 3 ) in cement raw materials. Different wavelength selection techniques are used to perform a comprehensive analysis of the model, comparing the performance of several wavelength selection techniques. The back-propagation neural network regression model based on particle swarm optimization algorithm was also applied to optimize the extracted and screened feature wavelengths, and the model prediction performance was checked and evaluated using R p and RMSE. In conclusion, the results indicate that NIR spectroscopy in combination with ML and chemometrics has great potential to effectively improve the prediction performance of oxide content in raw materials and highlight the importance of modeling and wavelength selection techniques. By enabling more accurate and efficient determination of oxide content in raw materials, NIR spectroscopy coupled with meta-modeling has the potential to revolutionize quality assurance practices in cement manufacturing.
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Excessive dietary fat intake is closely associated with an increased risk of obesity, type 2 diabetes, cardiovascular disease, gastrointestinal diseases, and certain types of cancer. The administration of multi-strain probiotics has shown a significantly beneficial effect on the mitigation of obesity induced by high-fat diets (HFDs). In this study, Amuc_1100, an outer membrane protein of Akkermansia muciniphila, was fused with green fluorescent protein and LPXTG motif anchor protein and displayed on the surface of Lactobacillus rhamnosus (pLR-GAA) and Lactobacillus plantarum (pLP-GAA), respectively. The localization of the fusion protein on the bacterial cell surface was confirmed via fluorescence microscopy and Western blotting. Both recombinant strains demonstrated the capacity to ameliorate hyperglycemia and decrease body weight gain in a dose-dependent manner. Moreover, daily oral supplementation of pLR-GAA or pLP-GAA suppressed the HFD-induced intestinal permeability by regulating the mRNA expressions of tight junction proteins and inflammatory cytokines, thereby reducing gut microbiota-derived lipopolysaccharide concentration in serum and mitigating damage to the gut, liver, and adipose tissue. Compared with Lactobacillus rhamnosus treatment, high-dose pLR-GAA restored the expression level of anti-inflammatory factor interleukin-10 in the intestine. In conclusion, our approach enables the maintenance of intestinal health through the use of recombinant probiotics with surface-displayed functional protein, providing a potential therapeutic strategy for HFD-induced obesity and associated metabolic comorbidities.
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INTRODUCTION: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. METHODS: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr), and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the correlations of iron indices, PTH, and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. RESULTS: The average ERI value was 10.3 ± 5.3 IU w-1 kg-1 (g/dL) -1. ERI was correlated to PTH, hepcidin, CHr, and TSAT (all p < 0.05). Hepcidin and PTH were closely correlated with each other (r = 0.28, p = 0.020). Analysis by PTH categories yielded a total association effect of 2.53 (95% CI: 0.27-4.85, p = 0.027) for high PTH subgroup versus the reference low subgroup. No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-third of the total association between PTH and ERI in hemodialysis population (33.6%, p = 0.025). CONCLUSION: Iron indices and PTH levels were related to ERI values. Hepcidin appeared to be closely correlated to PTH and partly mediate the association between PTH and ERI in hemodialysis population.
Subject(s)
Erythropoietin , Hepcidins , Iron , Parathyroid Hormone , Renal Dialysis , Humans , Parathyroid Hormone/blood , Renal Dialysis/adverse effects , Male , Middle Aged , Erythropoietin/blood , Female , Cross-Sectional Studies , Iron/blood , Aged , Hepcidins/blood , Drug Resistance , Adult , Ferritins/bloodABSTRACT
Background: Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain. Objectives: Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice. Designs: Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients. Methods: Data for advanced thymic carcinoma patients receiving immunotherapy and their metastases sites were collected for analysis from seven different hospitals between January 2015 and January 2023. Progression-free survival (PFS) and overall survival (OS) analyses were performed using the Kaplan-Meier method. Cox analysis was used to evaluate factors influencing survival. Results: The present study analyzed 136 advanced thymic carcinoma patients from seven different hospitals.The PFS for all patients receiving immunotherapy was 6.4 months, while the OS was 24.0 months. The objective response rate was different for patients with liver and non-liver metastases (11.9% versus 37.2%, p = 0.003). The disease control rate values were also different between the two groups (47.6% versus 80.9%, p = 0.037). The PFS for patients with liver metastases demonstrated poor immunotherapy efficacy compared to patients with non-liver metastases (3.0 versus 8.0 months, p < 0.0001). The OS was also significantly different between these two patient groups (16.1 versus 29.1 months, p = 0.009). Conclusion: Immunotherapy had poor efficacy in advanced thymic carcinoma patients with liver metastases.
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BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease worldwide. Autophagy plays a pivotal role in lipid metabolism; however, the mechanism underlying the reduced autophagic activity in MAFLD remains elusive. METHODS: Autophagy was monitored by TUNEL assay and immunofluorescence staining of LC3. The expression of autophagy-related proteins, PPARα, HDAC2, and HRD1 was detected by Western blot. The association between HDAC2 and PPARα promoter was assessed by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, and the HRD1-mediated ubiquitin-proteasomal degradation of HDAC2 was detected by co-immunoprecipitation (co-IP). The in vitro findings were validated in a hypoxia-induced MAFLD mouse model. Histological changes, fibrosis, and apoptosis in liver tissues were detected by hematoxylin and eosin staining, Masson's trichrome staining, and TUNEL assay. The immunoreactivities of key molecules were examined by IHC analysis. RESULTS: Hypoxia-suppressed autophagy in hepatocytes. Hypoxic exposure downregulated HRD1 and PPARα, while upregulating HDAC2 in hepatocytes. Overexpression of PPARα promoted hepatic autophagy, while knocking down HDAC2 or overexpressing HRD1 reduced hypoxia-suppressed autophagy in hepatocytes. Mechanistically, HDAC2 acted as a transcriptional repressor of PPARα, and HRD1 mediated the degradation of HDAC2 through the ubiquitin-proteasome pathway. Functional studies further showed that hypoxia-suppressed hepatic autophagy via the HRD1/HDAC2/PPARα axis in vitro and in vivo. CONCLUSION: HRD1-mediated ubiquitination of HDAC2 regulates PPARα-mediated autophagy and ameliorates hypoxia-induced MAFLD.
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BACKGROUND: C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. METHODS: Accordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords 'IL-8' or 'interleukin-8' or 'CXCL8', 'polymorphism' and 'cancer' or 'tumor'. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay. RESULTS: About 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079-1.459), Pheterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046-1.666), Pheterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P < 0.01), and also shown similar trend as compared to genotype-matched normal controls (P < 0.01). Finally, several limitations, such as the potential for publication bias or heterogeneity among the included studies should be paid attention. CONCLUSION: Current study suggested that the CXCL8 -353 and +781 polymorphisms may be associated with a greater risk of cancer, which might impact cancer prevention, diagnosis, or treatment through the different expression of CXCL8. At the same time, the +781 polymorphism may further offer value as a biomarker that can aid in the early identification and prognostic evaluation of oral cancer.
Subject(s)
Genetic Predisposition to Disease , Interleukin-8 , Mouth Neoplasms , Humans , Interleukin-8/genetics , Mouth Neoplasms/genetics , Case-Control Studies , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
BACKGROUND: Aspiration is a frequently observed complication in individuals diagnosed with acute ischemic stroke, leading to potentially severe consequences. However, the availability of predictive tools for assessing aspiration probabilities remains limited. Hence, our study aimed to develop and validate a nomogram for accurately predicting aspiration probability in patients with acute ischemic stroke. METHODS: We analyzed 30 potential risk factors associated with aspiration in 359 adult patients diagnosed with acute ischemic stroke. Advanced statistical techniques, such as Least absolute shrinkage and selection operator (LASSO) and Multivariate Logistic regression, were employed to identify independent predictors. Subsequently, we developed a nomogram prediction model based on these predictors, which underwent internal validation through 1000 bootstrap resampling. Two additional cohorts (Cohort A n = 64; Cohort B, n = 105) were included for external validation. The discriminatory power and calibration performance of the nomogram were assessed using rigorous methods, including the Hosmer-Lemeshow test, area under the receiver operating characteristic curve (AUC), calibration curve analyses, and decision curve analyses (DCA). RESULTS: The nomogram was established based on four variables: sputum suction, brain stem infarction, temporal lobe infarction, and Barthel Index score. The predictive model exhibited satisfactory discriminative ability, with an area under the receiver operating characteristic curve of 0.853 (95 % confidence interval, 0.795-0.910), which remained consistent at 0.852 (95 % confidence interval, 0.794-0.912) during the internal validation. The Hosmer-Lemeshow test (P = 0.394) and calibration curve demonstrated favorable consistency between the predicted and observed outcomes in the development cohort. The AUC was 0.872 (95 % confidence interval, 0.783-0.962) in validation cohort A and 0.877 (95 % confidence interval, 0.764-0.989) in validation cohort B, demonstrating sustained accuracy. DCA showed a good net clinical benefit of the nomogram. CONCLUSIONS: A nomogram for predicting the probability of aspiration in patients with acute ischemia has been successfully developed and validated.
Subject(s)
Ischemic Stroke , Nomograms , Humans , Male , Female , Ischemic Stroke/diagnosis , Aged , Middle Aged , Risk Factors , Risk Assessment/methods , Aged, 80 and over , Cohort Studies , Respiratory Aspiration/diagnosis , Respiratory Aspiration/etiologyABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and the development of non-alcoholic steatohepatitis (NASH) might cause irreversible hepatic damage. Hyperlipidemia (HLP) is the leading risk factor for NAFLD. This study aims to illuminate the causative contributor and potential mechanism of Kallistatin (KAL) mediating HLP to NAFLD. 221 healthy control and 253 HLP subjects, 62 healthy control and 44 NAFLD subjects were enrolled. The plasma KAL was significantly elevated in HLP subjects, especially in hypertriglyceridemia (HTG) subjects, and positively correlated with liver injury. Further, KAL levels of NAFLD patients were significantly up-regulated. KAL transgenic mice induced hepatic steatosis, inflammation, and fibrosis with time and accelerated inflammation development in high-fat diet (HFD) mice. In contrast, KAL knockout ameliorated steatosis and inflammation in high-fructose diet (HFruD) and methionine and choline-deficient (MCD) diet-induced NAFLD rats. Mechanistically, KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) by LRP6/GÉs/PKA/GSK3ß pathway through down-regulating peroxisome proliferator-activated receptor γ (PPARγ) and up-regulating kruppel-like factor four (KLF4), respectively. CGI-58 is bound to NF-κB p65 in the cytoplasm, and diminishing CGI-58 facilitated p65 nuclear translocation and TNFα induction. Meanwhile, hepatic CGI-58-overexpress reverses NASH in KAL transgenic mice. Further, free fatty acids up-regulated KAL against thyroid hormone in hepatocytes. Moreover, Fenofibrate, one triglyceride-lowering drug, could reverse hepatic steatosis by down-regulating KAL. These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.
Subject(s)
Non-alcoholic Fatty Liver Disease , Serpins , Humans , Mice , Rats , Animals , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Inflammation/metabolism , Mice, TransgenicABSTRACT
Cucurbitacin IIa is a triterpenoid isolated exclusively from Hemsleya plants and a non-steroidal anti-inflammatory drug that functions as the main ingredient of prescription Hemslecin capsules and tablets in China. Synthetic biology provides new strategies for production of such valuable cucurbitacins at a large scale; however, the biosynthetic pathway of cucurbitacin IIa has been unknown, and the heterologous production of cucurbitacins in galactose medium has been expensive and low yielding. In this study, we characterized the functions of genes encoding two squalene epoxidases (HcSE1-2), six oxidosqualene cyclases (HcOSC1-6), two CYP450s (HcCYP87D20 and HcCYP81Q59), and an acyltransferase (HcAT1) in cucurbitacin IIa biosynthesis by heterologous expression in Saccharomyces cerevisiae and Nicotiana benthamiana. We achieved high-level production of the key cucurbitacin precursor 11-carbonyl-20ß-hydroxy-Cuol from glucose in yeast via modular engineering of the mevalonate pathway and optimization of P450 expression levels. The resulting yields of 46.41 mg/l 11-carbonyl-20ß-hydroxy-Cuol and 126.47 mg/l total cucurbitacin triterpenoids in shake flasks are the highest yields yet reported from engineered microbes. Subsequently, production of 11-carbonyl-20ß-hydroxy-Cuol by transient gene expression in tobacco resulted in yields of 1.28 mg/g dry weight in leaves. This work reveals the key genes involved in biosynthesis of prescription cucurbitacin IIa and demonstrates that engineered yeast cultivated with glucose can produce high yields of key triterpenoid intermediates. We describe a low-cost and highly efficient platform for rapid screening of candidate genes and high-yield production of pharmacological triterpenoids.
Subject(s)
Biosynthetic Pathways , Nicotiana , Saccharomyces cerevisiae , Triterpenes , Nicotiana/genetics , Nicotiana/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Triterpenes/metabolism , Cucurbitacins/genetics , Cucurbitacins/metabolism , Plants, Genetically Modified/genetics , Metabolic Engineering/methods , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms. METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3. RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury. CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.
Subject(s)
Adenosine , Asthma , Disease Models, Animal , Gastrointestinal Microbiome , Homeostasis , Methyltransferases , Probiotics , Saccharomyces boulardii , Up-Regulation , Animals , Asthma/therapy , Asthma/metabolism , Asthma/immunology , Asthma/etiology , Asthma/microbiology , Methyltransferases/metabolism , Methyltransferases/genetics , Gastrointestinal Microbiome/immunology , Mice , Adenosine/metabolism , Adenosine/analogs & derivatives , Probiotics/administration & dosage , Probiotics/therapeutic use , Female , Fecal Microbiota Transplantation , Ovalbumin/immunology , Mice, Inbred BALB CABSTRACT
BACKGROUND: Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning has been used for disease risk prediction; however, it lacks adherence to evidence-based medicine standards. Identifying the underlying mechanisms behind disease risk prediction is important and required. METHODS: We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. FINDINGS: HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. CONCLUSIONS: HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. FUNDING: This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.
Subject(s)
Atrial Fibrillation , Deep Learning , Heart Rate , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Humans , Risk Assessment , Heart Rate/physiology , Male , Risk Factors , Female , Artificial Intelligence , Electrocardiography/methods , Aged , Middle Aged , Early DiagnosisABSTRACT
BACKGROUND: Modelling academic self-concept through second-order factors or bifactor structures is an important issue with substantive and practical implications; besides, the bifactor model has not been analysed with a Chinese sample and cross-cultural studies in the academic self-concept are scarce. Likewise, latent structure validity evidence using network psychometrics has not been carried out. AIMS: The aim of this study is twofold: to analyse (1) the internal structure of ASC through the Self-Description Questionnaire II-Short (SDQII-S) in Chinese and Spanish samples using two approaches, structural equation modelling and network psychometrics conducting an exploratory graph analysis; and (2) the measurement invariance of the best model across countries and investigate the cross-cultural differences in ASC. SAMPLE: The sample was composed by 651 adolescents. Seven models of ASC were tested. RESULTS: Results supported the multi-dimensional nature of the data as well as the reliability. The best-fitted model for the two subsamples was the three-factor ESEM model, but only the configural invariance of this model was supported across countries. The graph function shows that the school dimension appears more related to the verbal factor in the Spanish subsample and to the math dimension in the Chinese subsample. Likewise, the relationship between verbal and math factors in Spanish students is non-existent, but this connection is more relevant for Chinese students. CONCLUSION: These two differences may be behind the difficulty in finding invariance using SEM models. It is a question of the construct's nature, less related to analytical phenomena, and deserves deeper discussion.
Subject(s)
Cross-Cultural Comparison , Self Concept , Adolescent , Humans , Spain , Reproducibility of Results , Surveys and Questionnaires , Psychometrics/methods , ChinaABSTRACT
PURPOSE: Metabolic-associated fatty liver disease (MAFLD) is an aging-related disease. Obstructive sleep apnea (OSA) may cause MAFLD. This study aimed to explore whether or not intermittent hypoxia (IH), the hallmark of OSA, induces liver aging through oxidative stress. METHODS: C57BL/6J male mice were administered normal air (control), IH, or antioxidant tempol + IH daily for 6 weeks before the collection of serum and liver tissue samples. A histological examination was conducted to assess liver aging. ELISA was performed to measure liver function indicator levels in the serum and oxidative stress indicator activities in the liver. Western blot analysis was carried out to determine the protein expression of the markers related to oxidative stress, inflammation, and senescence. RESULTS: Compared with control, IH resulted in significant increases in serum ALT, AST, and TG levels in mice (all P < 0.001), along with lobular inflammation and accumulation of collagen and fat in the liver. The protein levels of inflammatory factors and senescent markers were significantly increased in the IH mouse liver compared with those in the control mouse liver. Meanwhile, IH significantly reduced SOD and CAT activities while enhancing p22phox and Nrf2 protein expression in mouse liver compared with control. Importantly, antioxidant therapy with tempol effectively abrogated the effects of IH on oxidative stress response and aging-related liver injury. CONCLUSIONS: Our findings suggest that IH induces liver inflammation and aging through oxidative stress. OSA may exacerbate target organ aging and participate in target organ damage. Strategies targeting oxidative stress may prevent and treat OSA-related MAFLD.
Subject(s)
Antioxidants , Cyclic N-Oxides , Sleep Apnea, Obstructive , Spin Labels , Mice , Male , Animals , Antioxidants/pharmacology , Mice, Inbred C57BL , Oxidative Stress/physiology , Liver/pathology , Hypoxia , Inflammation/complicationsABSTRACT
The excretion care robot's (ECR) accurate recognition of transfer-assisted actions is crucial during its usage. However, transfer action recognition is a challenging task, especially since the differentiation of actions seriously affects its recognition speed, robustness, and generalization ability. We propose a novel approach for transfer action recognition assisted by a bidirectional long- and short-term memory (Bi-LSTM) network combined with a multi-head attention mechanism. Firstly, we utilize posture sensors to detect human movements and establish a lightweight three-dimensional (3D) model of the lower limbs. In particular, we adopt a discrete extended Kalman filter (DEKF) to improve the accuracy and foresight of pose solving. Then, we construct an action prediction model that incorporates a fused Bi-LSTM with Multi-head attention (MHA Bi-LSTM). The MHA extracts key information related to differentiated movements from different dimensions and assigns varying weights. Utilizing the Bi-LSTM network effectively combines past and future information to enhance the prediction results of differentiated actions. Finally, comparisons were made by three subjects in the proposed method and with two other time series based neural network models. The reliability of the MHA Bi-LSTM method was verified. These experimental results show that the introduced MHA Bi-LSTM model has a higher accuracy in predicting posture sensor-based excretory care actions. Our method provides a promising approach for handling transfer-assisted action individual differentiation in excretion care tasks.
Subject(s)
Body Fluids , Robotics , Humans , Individuality , Reproducibility of Results , Lower ExtremityABSTRACT
OBJECTIVE: The widespread use of assisted reproductive technology (ART) has led to an increased twin pregnancy rate and increased risk of pregnancy complications. Pre-pregnancy body mass index (BMI) and maternal age are both risk factors for pregnancy complications. This study aimed to explore whether there is an interaction effect between pre-pregnancy BMI and maternal age on pregnancy complications in women with twin pregnancies after ART. METHODS: Data of 445,750 women with twin pregnancies after ART were extracted from the National Vital Statistics System (NVSS) database in 2016-2021 in this retrospective cohort study. Univariate and multivariate logistic regression analyses were used to explore (1) the associations between pre-pregnancy BMI, maternal age, and total pregnancy complications; (2) interaction effect between pre-pregnancy BMI and maternal age on total pregnancy complications; and (3) this interaction effect in parity, race, gestational weight gain (GWG), and preterm birth subgroups. The evaluation indexes were odds ratios (ORs), relative excess risk of interaction (RERI), attributable proportions of interaction (AP), and synergy index (S) with 95% confidence intervals (CIs). RESULTS: A total of 6,827 women had pregnancy complications. After adjusting for the covariates, compared with women had non-AMA and pre-pregnancy BMI <25 kg/m2, higher maternal age combined with higher pre-pregnancy BMI was associated with higher odds of total pregnancy complications [OR = 2.16, 95%CI: (1.98-2.36)]. The RERI (95% CI) was 0.22 (0.04-0.41), AP (95% CI) was 0.10 (0.02-0.19), and S (95% CI) was 1.24 (1.03-1.49). Subgroup analysis results indicated that the potential additive effect between pre-pregnancy BMI and maternal age on total pregnancy complications was also found in women with different race, multipara/unipara, GWG levels, or preterm births/non-preterm births (all p < 0.05). CONCLUSION: Pre-pregnancy BMI and maternal age may have an additive effect on the odds of pregnancy-related complications in women with twin pregnancy after ART.