Purpose
: Heart rate is the most commonly used indicator in clinical medicine to assess the functionality of the cardiovascular system. Most studies have focused on age-based equations to estimate ...the maximal heart rate, neglecting multiple factors that affect the accuracy of the prediction.
Methods
: We studied 121 middle-aged adults at an average age of 57.2years with an average body mass index (BMI) of 25.9. The participants performed on a power bike with a starting wattage of 0W that was increased by 25W every 3min until the experiment terminated. Ambulatory blood pressure and electrocardiography were monitored through gas metabolic analyzers for safety concerns. Six descriptive characteristics of participants were observed, which were further analyzed using a multivariate regression model and an artificial neural network (ANN).
Results
: The input variables for the multivariate regression model and ANN were selected by correlation for the reduction of dimension. The accuracy of estimation by multivariate regression model and ANN was 9.74 and 9.42%, respectively, which outperformed the traditional age-based model (with an accuracy of 10.31%).
Conclusion
: This study provides comprehensive approaches to estimate the maximal heart rate using multiple indicators, revealing that both the multivariate regression model and ANN incorporated with age, resting heart rate (RHR), and second-order heart rate (SOHR) are more accurate than univariate models.
Background:
The cause of sarcopenia has been observed over decades by clinical trials, which, however, are still insufficient to systematically unravel the enigma of how resistance exercise mediates ...skeletal muscle mass.
Materials and Methods:
Here, we proposed a minimal regulatory network and developed a dynamic model to rigorously investigate the mechanism of sarcopenia. Our model is consisted of eight ordinary differential equations and incorporates linear and Hill-function terms to describe positive and negative feedbacks between protein species, respectively.
Results:
A total of 720 samples with 10 scaled intensities were included in simulations, which revealed the expression level of AKT (maximum around 3.9-fold) and mTOR (maximum around 5.5-fold) at 3, 6, and 24 h at high intensity, and non-monotonic relation (ranging from 1.2-fold to 1.7-fold) between the graded intensities and skeletal muscle mass. Furthermore, continuous dynamics (within 24 h) of AKT, mTOR, and other proteins were obtained accordingly, and we also predicted the delaying effect with the median of maximized muscle mass shifting from 1.8-fold to 4.6-fold during a 4-fold increase of delay coefficient.
Conclusion:
The
de novo
modeling framework sheds light on the interdisciplinary methodology integrating computational approaches with experimental results, which facilitates the deeper understandings of exercise training and sarcopenia.
Prediction of delivery is important for assessing due dates, providing adequate prenatal care, and suggesting appropriate interventions in preterm and post-term pregnancies. Recent metabolomic ...findings suggested that the temporal abundance information of metabolome can be used to predict delivery timing with high accuracy in a cohort of healthy women. However, a targeted and quantitative assay is required to further validate the clinical performance and utility of this group of metabolomic candidates in delivery prediction with a larger and independent cohort.
LC-MS/MS quantitative assays were applied to determine the plasma concentrations of four steroid metabolites, including oestriol-16-glucuronide (E3-16-Gluc), 17-alpha-hydroxyprogesterone (17-OHP), tetrahydrodeoxycorticosterone (THDOC), and androstane-3,17-diol (A-3,17-Diol) in asymptomatic women of singleton pregnancies (≥30
th
gestational weeks). Subsequent statistical analysis was conducted to assess the performance of the above candidates in delivery prediction.
Using LC-MS/MS, four steroids were separated and quantified in 5.5 min. The coefficients of variation (CVs) of the four analytes at the lower limit of quantification ranged from 7.9% to 14.6%, with the R
2
values greater than 0.990 in the calibration curves. Of the 585 recruited pregnant women who ended up with spontaneous delivery, 17.1% and 82.9% of the subjects delivered within and after 7 days since plasma collection, respectively. In the receiver operator curve analysis, the gestational age-adjusted area under the curve of the combined measurements of E3-16-Gluc and 17-OHP was 0.69 (95% CI: 0.60-0.76), with the sensitivity of 87.0% (95% CI: 78.8%-92.9%) and specificity of 60.2% (95% CI: 55.7%-64.6%). Moreover, the positive and the negative predictive values were 28.3%-34.0% and 93.1%-97.4% respectively for this combined panel.
We performed analytical and clinical validation of a quantitation LC-MS/MS panel for the four steroids in the plasma of pregnant women. The steroid metabolites panel of E3-16-Gluc and 17-OHP was potentially useful for predicting delivery within one week in asymptomatic women of singleton pregnancies.
Key messages
A quantitative LC-MS/MS assay for determining the plasma levels of 17-OHP, THDOC, A-3,17-Diol and E3-16-Gluc was developed and validated, in order to evaluate their predictive performance in asymptomatic delivery of singleton pregnancy. The levels of E3-16-Gluc and 17-OHP were found to be significantly elevated at the time of sampling in women that delivered within one week and their combinational testing may be potentially useful in delivery prediction.
Alzheimer's disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. ...Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action.
The present study aimed to clarify CR's active constituents and its pharmacological mechanisms in treating AD.
A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia.
The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR's efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation.
The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.
Camellia oleifera is an economic tree species in southern China and is famous for its oil. The surrounding climate is filtered by the tree itself, resulting in the canopy microclimate, which affects ...the growth and fruit quality of C. oleifera. This study investigated the effect of canopy positions on microclimate and fruit growth, maturation and qualities by comparing the differences in canopy position. This study also considered the relationship between microclimate and fruit qualities during the oil conversion period. The fruit qualities and microclimate were studied by dividing the canopy into two vertical layers and horizontal layers, creating the following canopy positions: upper outer canopy (UO), upper inner canopy (UI), lower outer canopy (LO) and lower inner canopy (LI). The light intensity increased significantly from inside to outside and from top to bottom in the canopy; however, there were no significant differences in temperature and relative humidity. At maturity, the moisture content of fruits and kernels in UO and LO was approximately <5% of those in UI and LI. The soluble sugar content increased by 10.90%, 8.47% and 6.84% in UO, UI and LO in November, while no significant change was observed in LI. The kernel oil content (KOC) obtained a higher value in UO and UI at maturity. However, KOC decreased by 5.16%, 3.02%, 3.10% and 0.67% in UO, UI, LO and LI in November. Light intensity in September and October was correlated, and temperature and relative humidity in August and September were correlated.
Von Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field ...fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease.
Subjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age ≤ 50 years old.
Subjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis.
67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484).
OCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.
To determine the roles of nuclear localization of pro-caspase-1 in human aortic endothelial cells (HAECs) activated by proatherogenic lipid lysophosphatidylcholine (LPC), we examined cytosolic and ...nuclear localization of pro-caspase-1, identified nuclear export signal (NES) in pro-caspase-1 and sequenced RNAs. We made the following findings: 1) LPC increases nuclear localization of procaspase-1 in HAECs. 2) Nuclear pro-caspase-1 exports back to the cytosol, which is facilitated by a leptomycin B-inhibited mechanism. 3) Increased nuclear localization of pro-caspase-1 by a new NES peptide inhibitor upregulates inflammatory genes in oxidative stress and Th17 pathways; and SUMO activator N106 enhances nuclear localization of pro-caspase-1 and caspase-1 activation (p20) in the nucleus. 4) LPC plus caspase-1 enzymatic inhibitor upregulates inflammatory genes with hypercytokinemia/hyperchemokinemia and interferon pathways, suggesting a novel capsase-1 enzyme-independent inflammatory mechanism. 5) LPC in combination with NES inhibitor and caspase-1 inhibitor upregulate inflammatory gene expression that regulate Th17 activation, endotheli-1 signaling, p38-, and ERK- MAPK pathways. To examine two hallmarks of endothelial activation such as secretomes and membrane protein signaling, LPC plus NES inhibitor upregulate 57 canonical secretomic genes and 76 exosome secretomic genes, respectively, promoting four pathways including Th17, IL-17 promoted cytokines, interferon signaling and cholesterol biosynthesis. LPC with NES inhibitor also promote inflammation via upregulating ROS promoter CYP1B1 and 11 clusters of differentiation (CD) membrane protein pathways. Mechanistically, all the LPC plus NES inhibitor-induced genes are significantly downregulated in CYP1B1-deficient microarray, suggesting that nuclear caspase-1-induced CYP1B1 promotes strong inflammation. These transcriptomic results provide novel insights on the roles of nuclear caspase-1 in sensing DAMPs, inducing ROS promoter CYP1B1 and in regulating a large number of genes that mediate HAEC activation and inflammation. These findings will lead to future development of novel therapeutics for cardiovascular diseases (CVD), inflammations, infections, transplantation, autoimmune disease and cancers. (total words: 284).
With the expansion of the epidemic, online multimedia teaching has become a common trend. The reasoning model of multimedia teaching evaluation is a useful tool to infer the result of teaching ...effects and predict the tendency. However, the ambiguity in the linguistic-valued evaluation leads to reasoning problems always in the context with uncertainty. To make the reasoning model better deal with multiple and multidimensional reasoning problems in uncertainty environment, while considering both positive evidence and negative evidence at the same time, this paper mainly focuses on a linguistic truth-valued intuitionistic fuzzy layered aggregation (LTV-IFLA) reasoning method. First, based on the layered linguistic truth-valued intuitionistic fuzzy lattice (LTV-IFL), we realize aggregating the linguistic truth-valued information through the layered average aggregation (LAA) operator presented by this paper. Furthermore, a layered weighted average aggregation (LWAA) operator is proposed to consider setting different weights to achieve personalization of the reasoning results. Finally, a multiple multidimensional reasoning model which simulates the reasoning of human language is presented to illustrate the method’s rationality and validity.
Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% of the population and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD ranges from simple steatosis ...(non-alcoholic fatty liver) to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs) and monocyte-derived macrophages, act as key players in the progression of NAFLD. Caspases are a family of endoproteases that provide critical connections to cell regulatory networks that sense disease risk factors, control inflammation, and mediate inflammatory cell death (pyroptosis). Caspase-11 can cleave gasdermin D (GSDMD) to induce pyroptosis and specifically defends against bacterial pathogens that invade the cytosol. However, it's still unknown whether high fat diet (HFD)-facilitated gut microbiota-generated cytoplasmic lipopolysaccharides (LPS) activate caspase-11 and promote NAFLD.
To examine this hypothesis, we performed liver pathological analysis, RNA-seq, FACS, Western blots, Seahorse mitochondrial stress analyses of macrophages and bone marrow transplantation on HFD-induced NAFLD in WT and Casp11-/- mice.
Our results showed that 1) HFD increases body wight, liver wight, plasma cholesterol levels, liver fat deposition, and NAFLD activity score (NAS score) in wild-type (WT) mice; 2) HFD increases the expression of caspase-11, GSDMD, interleukin-1β, and guanylate-binding proteins in WT mice; 3) Caspase-11 deficiency decreases fat liver deposition and NAS score; 4) Caspase-11 deficiency decreases bone marrow monocyte-derived macrophage (MDM) pyroptosis (inflammatory cell death) and inflammatory monocyte (IM) surface GSDMD expression; 5) Caspase-11 deficiency re-programs liver transcriptomes and reduces HFD-induced NAFLD; 6) Caspase-11 deficiency decreases extracellular acidification rates (glycolysis) and oxidative phosphorylation (OXPHOS) in inflammatory fatty acid palmitic acid-stimulated macrophages, indicating that caspase-11 significantly contributes to maintain dual fuel bioenergetics-glycolysis and OXPHOS for promoting pyroptosis in macrophages. These results provide novel insights on the roles of the caspase-11-GSDMD pathway in promoting hepatic macrophage inflammation and pyroptosis and novel targets for future therapeutic interventions involving the transition of NAFLD to NASH, hyperlipidemia, type II diabetes, metabolic syndrome, metabolically healthy obesity, atherosclerotic cardiovascular diseases, autoimmune diseases, liver transplantation, and hepatic cancers.
The molecular mechanisms underlying chronic kidney disease (CKD) transition to end-stage renal disease (ESRD) and CKD acceleration of cardiovascular and other tissue inflammations remain poorly ...determined.
We conducted a comprehensive data analyses on 7 microarray datasets in peripheral blood mononuclear cells (PBMCs) from patients with CKD and ESRD from NCBI-GEO databases, where we examined the expressions of 2641 secretome genes (SG).
1) 86.7% middle class (molecular weight >500 Daltons) uremic toxins (UTs) were encoded by SGs; 2) Upregulation of SGs in PBMCs in patients with ESRD (121 SGs) were significantly higher than that of CKD (44 SGs); 3) Transcriptomic analyses of PBMC secretome had advantages to identify more comprehensive secretome than conventional secretomic analyses; 4) ESRD-induced SGs had strong proinflammatory pathways; 5) Proinflammatory cytokines-based UTs such as IL-1β and IL-18 promoted ESRD modulation of SGs; 6) ESRD-upregulated co-stimulation receptors CD48 and CD58 increased secretomic upregulation in the PBMCs, which were magnified enormously in tissues; 7) M1-, and M2-macrophage polarization signals contributed to ESRD- and CKD-upregulated SGs; 8) ESRD- and CKD-upregulated SGs contained senescence-promoting regulators by upregulating proinflammatory IGFBP7 and downregulating anti-inflammatory TGF-β1 and telomere stabilizer SERPINE1/PAI-1; 9) ROS pathways played bigger roles in mediating ESRD-upregulated SGs (11.6%) than that in CKD-upregulated SGs (6.8%), and half of ESRD-upregulated SGs were ROS-independent.
Our analysis suggests novel secretomic upregulation in PBMCs of patients with CKD and ESRD, act synergistically with uremic toxins, to promote inflammation and potential disease progression. Our findings have provided novel insights on PBMC secretome upregulation to promote disease progression and may lead to the identification of new therapeutic targets for novel regimens for CKD, ESRD and their accelerated cardiovascular disease, other inflammations and cancers. (Total words: 279).
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