Miracle-dz/UniFAR-FTUs huggingface dataset:
Vancomycin-induced gut microbiota dysbiosis aggravates allergic rhinitis in mice by altered short-chain fatty acids

Objective This study aims to explore how gut microbiota dysbiosis affects allergic rhinitis (AR) and whether short-chain fatty acids (SCFAs) play a role in this process. Methods A mouse gut microbiota dysbiosis model was established by adding vancomycin to drinking water for 2 weeks before ovalbumin (OVA) sensitization. Then an OVA-alum AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes in nasal and colon tissues of AR mice. Serum levels of total-IgE, OVA-sIgE, IL-4, IL-5, IL-10, and TGF-β1 were measured. The composition and diversity of the mouse gut microbiota were observed by 16S rDNA sequencing. Levels of SCFAs in feces were determined using SCFA-targeted metabolomics. Sodium butyrate (NaB) was added daily to mice on a low-fiber basal diet 2 weeks before the first sensitization, until the end of the study. Results After gut microbiota dysbiosis, serum levels of the total IgE, OVA-sIgE, IL-4, and IL-5 in AR mice were significantly increased (p < 0.01), compared with the control group. The composition and diversity of gut microbiota were significantly altered after gut microbiota dysbiosis, with the fecal SCFAs significantly reduced as well. The reduced bacterial genera after gut microbiota dysbiosis, such as Ruminococcus and Lactobacillus, were significantly and positively correlated with SCFAs. In contrast, the increased genera in the Van group, such as Escherichia-Shigella and Klebsiella, were significantly negatively correlated with SCFAs in feces. NaB treatment significantly reduced total-IgE, OVA-sIgE, IL-4, and IL-5 levels in serum, and inflammatory infiltration of the nasal and colon mucosa. In addition, serum levels of IL-10 and TGF-β1 increased significantly after NaB treatment (p < 0.01). Foxp3 protein in the colon was upregulated considerably after NaB intervention (p < 0.01). Conclusion Vancomycin-induced gut microbiota dysbiosis increased susceptibility and severity of AR, which is significantly related to reduced SCFA-producing bacteria, fecal SCFAs, and specific bacterial taxa. In addition, it was found that NaB alleviated low dietary fiber base-fed symptoms and immune status in AR mice.
Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome

Background: Fluid regimens in acute respiratory distress syndrome (ARDS) are conflicting. The amount of fluid and positive end-expiratory pressure (PEEP) level may interact leading to ventilator-induced lung injury (VILI). We therefore evaluated restrictive and liberal fluid strategies associated with low and high PEEP levels with regard to lung and kidney damage, as well as cardiorespiratory function in endotoxin-induced ARDS. Methods: Thirty male Wistar rats received an intratracheal instillation of Escherichia coli lipopolysaccharide. After 24 h, the animals were anesthetized, protectively ventilated (VT = 6 ml/kg), and randomized to restrictive (5 ml/kg/h) or liberal (40 ml/kg/h) fluid strategies (Ringer lactate). Both groups were then ventilated with PEEP = 3 cmH2O (PEEP3) and PEEP = 9 cmH2O (PEEP9) for 1 h (n = 6/group). Echocardiography, arterial blood gases, and lung mechanics were evaluated throughout the experiments. Histologic analyses were done on the lungs, and molecular biology was assessed in lungs and kidneys using six non-ventilated animals with no fluid therapy. Results: In lungs, the liberal group showed increased transpulmonary plateau pressure compared with the restrictive group (liberal, 23.5 ± 2.9 cmH2O; restrictive, 18.8 ± 2.3 cmH2O, p = 0.046) under PEEP = 9 cmH2O. Gene expression associated with inflammation (interleukin [IL]-6) was higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.006) and restrictive-PEEP9 (p = 0.012), Regardless of the fluid strategy, lung mechanical power and the heterogeneity index were higher, whereas birefringence for claudin-4 and zonula-ocludens-1 gene expression were lower in the PEEP9 groups. Perivascular edema was higher in liberal groups, regardless of PEEP levels. Markers related to damage to epithelial cells [club cell secreted protein (CC16)] and the extracellular matrix (syndecan) were higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.010 and p = 0.024, respectively). In kidneys, the expression of IL-6 and neutrophil gelatinase-associated lipocalin was higher in PEEP9 groups, regardless of the fluid strategy. For the liberal strategy, PEEP = 9 cmH2O compared with PEEP = 3 cmH2O reduced the right ventricle systolic volume (37%) and inferior vena cava collapsibility index (45%). Conclusion: The combination of a liberal fluid strategy and high PEEP led to more lung damage. The application of high PEEP, regardless of the fluid strategy, may also be deleterious to kidneys.
p62/Sqstm1 rescue in muscle retards the progression of steatohepatitis in p62/Sqstm1-null mice fed a high-fat diet

Introduction: Obesity is a risk factor for many diseases because it leads to a reduction in skeletal muscle mass and promotes insulin resistance. p62/Sqstm1-knockout mice are a model of metabolic syndrome; show obesity, insulin resistance, and non-alcoholic fatty liver (NAFL); and develop non-alcoholic steatohepatitis (NASH) in response to the feeding of a high-fat diet (HFD). These phenotypes suggest that muscle p62 may prevent obesity-induced muscle dysfunction. In the present study, we aimed to determine the effects of muscle p62 on skeletal muscle mass, muscle strength, insulin resistance, and NASH pathology. Methods: We generated muscle-specific p62 gene rescue mice (p62-mRes), which express p62 only in muscle and were derived from p62-knock out mice (p62 KIKI ) using the cre/loxp system. p62 KIKI and p62-mRes mice were fed an HFD for 20 weeks and their phenotypes were compared. Results: HFD-feeding caused severe obesity in both p62 KIKI and p62-mRes mice, but there was no effect of muscle p62 on body mass. Limb skeletal muscle mass, grip strength, and the cross-sectional area of muscle fibers were higher in p62-mRes mice than in p62 KIKI . The glucose tolerance and insulin sensitivity of the p62-mRes mice were also superior. The protein expression of mechanistic target of rapamycin, which promotes muscle protein synthesis, and GLUT4, a glucose transporter in skeletal muscle, were higher in the p62-mRes mice. p62 KIKI mice developed severe NASH when fed an HFD, but the progression of NASH was retarded by p62 gene rescue in muscle, and the expression of Tgf-β1, which encodes a factor that promotes hepatic fibrosis, was reduced. Conclusion: Rescue of muscle-specific p62 in the whole-body p62 knock-out mice ameliorates the insulin resistance and retards the progression of NASH caused by systemic p62 ablation.
A comparison of three‐dimensional embedded strain transducers, compression tested within the same strain field while offset at an angle with the principal axes

Abstract: The strain tensor and principal strains were derived for a range of different patterns of three‐dimensional strain transducers. The precisions of the estimates of these values were based on the Monte Carlo simulation applied to experimental work that was conducted on strain transducers tested within the same strain field. The estimates of precision were also determined theoretically and compared with results based on experimental findings. Results suggest that the tetrahedron transducers in experimental work do not perform as well as rectangular patterns and that estimates of principal strains, which were not coincident with the axes of the transducer, showed slight discrepancies.
Evaluation of the in vitro antioxidant and antitumor activity of extracts from Camellia fascicularis leaves

Camellia fascicularis is a unique plant rich in bioactive components. However, the isolation of the active substances in C. fascicularis leaves via sequential extraction with solvents of different polarity and the determination of their antioxidant and antitumor activities have not been reported. In this study, the total methanol extract of C. fascicularis leaves was sequentially extracted with different polar solvents, and the corresponding petroleum ether extract (PEE), ethyl acetate extract (EAE), and water extract (WE) were analyzed for their contents in active substances such as flavonoids, polyphenols, polysaccharides, and saponins. The antioxidant ability of the polar extracts was investigated by determining their reducing power and the radical scavenging rate on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals, and CCK-8 and Annexin-FITC/propidium iodide staining assays were conducted to investigate their inhibitory effects on HCCLM6 and HGC27 tumor cells. The results showed that PEE had a high saponin content of 197.35 ± 16.21 mg OAE/g, while EAE and WE exhibited a relatively higher polysaccharide content of 254.37 ± 1.99 and 373.27 ± 8.67 mg GE/g, respectively. The EAE demonstrated the greatest reducing power and the strongest clearing abilities on ABTS and DPPH radicals with respective EC50 values of 343.45 ± 20.12 and 14.07 ± 0.06 μg/ml. Moreover, the antitumor ability of the different polar extracts was dose-dependent, with WE showing the most potent inhibitory ability against HCCLM6 and HGC27 cells.
Forebrain control of breathing: Anatomy and potential functions

The forebrain plays important roles in many critical functions, including the control of breathing. We propose that the forebrain is important for ensuring that breathing matches current and anticipated behavioral, emotional, and physiological needs. This review will summarize anatomical and functional evidence implicating forebrain regions in the control of breathing. These regions include the cerebral cortex, extended amygdala, hippocampus, hypothalamus, and thalamus. We will also point out areas where additional research is needed to better understand the specific roles of forebrain regions in the control of breathing.
An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats

Aim: Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy that results in death from right ventricular failure (RVF). There is limited understanding of the molecular mechanisms of RVF in PAH. Methods: In a PAH-RVF model induced by injection of adult male rats with monocrotaline (MCT; 60 mg/kg), we performed mass spectrometry to identify proteins that change in the RV as a consequence of PAH induced RVF. Bioinformatic analysis was used to integrate our previously published RNA sequencing data from an independent cohort of PAH rats. Results: We identified 1,277 differentially regulated proteins in the RV of MCT rats compared to controls. Integration of MCT RV transcriptome and proteome data sets identified 410 targets that are concordantly regulated at the mRNA and protein levels. Functional analysis of these data revealed enriched functions, including mitochondrial metabolism, cellular respiration, and purine metabolism. We also prioritized 15 highly enriched protein:transcript pairs and confirmed their biological plausibility as contributors to RVF. We demonstrated an overlap of these differentially expressed pairs with data published by independent investigators using multiple PAH models, including the male SU5416-hypoxia model and several male rat strains. Conclusion: Multiomic integration provides a novel view of the molecular phenotype of RVF in PAH which includes dysregulation of pathways involving purine metabolism, mitochondrial function, inflammation, and fibrosis.
The Structure of Turbulence in a Supersonic Shock-Wave/Boundary-Layer Interaction

This paper reports the experimental results from a detailed investigation of the turbulent flowfields in supersonic shock-wave/boundary-layer interactions at Af=2.25. The interactions were produced by twodimensional compression corners having angles of 8, 13, and 18 deg, the flows being respectively attached, incipiently separated, and separated. Turbulence data from a laser velocimeter and a constant-temperature, hotwire anemometer are presented along with a mean flow survey from wall and pitot-static pressures. Qualitative aspects of the turbulence deduced from spectral analysis and high-speed schlieren pictures are also discussed. It is shown that a large amount of the turbulent energy is contained in large-scale structures that are still observed downstream of the interacting region, despite the severe pressure gradient. The lateral extent of these structures is of the order of one boundary-layer thickness and is roughly half of their longitudinal scale. A low-frequency unsteadiness is associated with the existence of a separation bubble, but does not affect the rest of the flow. The Reynolds shear stress is reduced in the vicinity of the separation bubble where the spatial derivatives of the normal stresses become significant.
A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer

Background While the efficacy of immune checkpoint inhibitors (ICIs) is increasingly recognized in advanced gastric cancer (aGC), overall survival (OS) has not been consistently improved across the different randomized controlled trials (RCTs). This meta-analysis aimed to quantify the efficacy and safety of ICI and explore potential predictive tumor tissue biomarkers in aGC. Methods A random-effect pairwise meta-analysis was used to evaluate the primary outcome of OS. Sensitivity analysis was performed to investigate the effects of ICIs on PD-L1 status, TMB, MSI-H, and the Asian patient population. We extracted the OS Kaplan–Meier curves from the included trials to compare the effect of PD-L1 status on response to ICIs using DigitizeIt 2.5 and Guyot’s algorithm. Results A pairwise meta-analysis of seven RCTs included in this study showed that ICIs were more effective than the comparator in improving OS (pooled HR: 0.84). We demonstrated that PD-1 ICIs were additive when combined with the comparator arm (pooled HR: 0.79). A sensitivity analysis showed that PD-1 ICIs were associated with better OS outcomes in the Asian patient population as monotherapy (pooled HR: 0.66) or in combination with chemotherapy (pooled HR: 0.83). We demonstrated that tumors with PD-L1 ≥1 (P = 0.02) and PD-L1 ≥10 (P = 0.006) derived OS benefit from ICI monotherapy. Equally, MSI-H (P <0.00001) and TMB-high (P <0.0001) tumors derived favorable survival benefits from ICIs. Conclusions and relevance The results of this meta-analysis suggest that ICIs result in improved OS outcomes in aGC. The benefits varied with different ethnicities, class of ICI, PD-L1 expression, MSI status, and TMB Systematic Review Registration https://www.crd. york.ac. uk/prospero, identifier (CRD42019137829).
Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway

High invasiveness is a biological and clinical characteristic of glioblastoma and predicts poor prognosis of patients. Quercetin, a natural flavonoid compound, exhibits anticancer activity. However, we have a limited understanding of the possible underlying mechanism of quercetin in glioblastoma. In this study, we investigated the anticancer effect of quercetin in human glioblastoma cells. Our results showed that quercetin markedly suppressed the viability of glioblastoma cells in vitro and in vivo, and significantly inhibited glioblastoma cell migration and invasion. Moreover, quercetin reversed EMT-like mesenchymal phenotype and reduced the expression levels of EMT-related markers. Furthermore, we found that quercetin suppressed GSK-3β/β-catenin/ZEB1 signaling in glioblastoma. Taken together, our results demonstrate that quercetin inhibited migration and invasion of human glioma cells by suppressing GSK3β/β-catenin/ZEB1 signaling. Our study provides evidence that quercetin is a promising therapeutic natural compound to treat glioblastoma.
Relations of postural change in blood pressure with hypertension-mediated organ damage in middle-aged adults of the Framingham heart study: A cross-sectional study

Background Dysregulation of compensatory mechanisms to regulate blood pressure (BP) upon postural change is a phenotype of BP variability and an emerging risk factor for cardiovascular outcomes. Materials and methods We assessed postural change in BP (starting 2 min after standing from a supine position), carotid-femoral pulse wave velocity (cfPWV), and markers of hypertension-mediated organ damage (HMOD) in the heart, kidney, and brain in Framingham Third Generation, Omni-2, and New Offspring Spouse Cohort participants. We related vascular measures (postural change in BP measures and cfPWV) with HMOD in 3,495 participants (mean age 47 years, 53% women) using multivariable logistic and linear regression models. Results In multivariable-adjusted models, we did not observe significant associations of vascular measures with presence of left ventricular hypertrophy, albuminuria, covert brain infarcts, or white matter hyperintensities (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). In multivariable models, greater cfPWV (est. β = 0.11 ± 0.03; P < 0.001), but not postural change in BP measures (Bonferroni-adjusted P-values > 0.05/20 > 0.0025), was associated with higher white matter free water using brain magnetic resonance imaging. In multivariable models, greater postural change in pulse pressure was associated with higher urinary albumin-creatinine ratio (est. β = 0.07 ± 0.02; P < 0.001). No other postural change in BP measure was associated with urinary albumin-creatinine ratio (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). In sex-specific analyses, higher cfPWV was associated with higher urinary albumin-creatinine ratio in men (est. β: 0.11 ± 0.04; P = 0.002) but not in women (est. β: 0.03 ± 0.03; P = 0.44). We also observed marginal to strong effect modification by above vs. at/below median postural change in BP for the association of cfPWV with urinary albumin−creatinine ratio (Bonferroni-adjusted interaction P < 0.001–0.01). Vascular measures were not related to left ventricular mass index or fractional anisotropy (Bonferroni-adjusted P-values > 0.05/20 > 0.0025). Conclusion Baroreflex dysfunction is associated with greater subclinical kidney damage. Additionally, relations of higher aortic stiffness with greater kidney damage may be modified by associated baroreflex dysregulation.
Particle Interpretations and Green Functions for a Free Scalar Field

The formalism of Ashtekar and Magnon [2] for the deﬁnition of particles in quantum ﬁeld theory in curved spacetime is further developed. The relation between basic objects of this formalism (e.g., the complex structure) and diﬀerent Green functions is found. It allows one to derive composition laws for Green functions. The relation of two deﬁnitions of particles is reformulated in the formalism and the base-independent Bogoljubov transformation is expressed using quantities which are derivable directly from the “in-out” Green function.
β-sitosterol inhibits trimethylamine production by regulating the gut microbiota and attenuates atherosclerosis in ApoE–/– mice

The intestinal microbial metabolite trimethylamine (TMA), which is activated by flavin monooxygenase (FMO) to produce trimethylamine-N-oxide (TMAO), has been implicated in the pathogenesis of atherosclerosis (AS), leading to the development of therapeutic strategies for AS. This study aimed to investigate whether β-sitosterol can inhibit TMA production in ApoE–/– mice by reshaping the gut microbial structure. 16S rRNA sequencing of the gut microbiota showed that β-sitosterol has beneficial effects on intestinal flora function, especially the inhibition of bacteria genera that contain the gene cholintrimethylamine lyase, which is responsible for the major pathway for TMA production. In parallel, β-sitosterol effectively reduced the TMA, FMO3, and TMAO levels while ameliorating the atherosclerotic plaques of AS mice. Moreover, β-sitosterol could alleviate cholesterol metabolism and the inflammatory response, and improve the antioxidant defense capacity. These studies offer new insights into the mechanisms responsible for the antiatherosclerotic effects of β-sitosterol, which targets the microbiota-metabolism-immunity axis as a possible therapy for AS.
A review on flexion angle in high-flexion total knee arthroplasty for indonesian’s need

Total Knee Arthroplasty (TKA) proposed as an alternative treatment for damaged knee joints of humans is reviewed. The commercial application of TKA can help patients to improve their daily normal activities. Here the high-flex type total knee arthroplasty (High-Flex TKA) is typically designed for the patient’s convenience on which the greater range of motion can be adjusted for extreme activities such as Seiza and Muslim praying. However, the present High-Flex TKAs have not fulfilled the needs of Indonesians for religious activities with a flexion angle of 150°–165°. Therefore, this review aims to examine the flexion range of High-Flex TKAs proposed for the needs of Indonesians. This study is a narrative review, all studies published and reviewed are related to the range of flexion angles on the use of products from many manufacturers and various types that have been used by patients, as well as the development of a CAD-based TKA design. It was proposed in the present study that the flexion angle on High-Flex TKAs may be optimized by thickening the posterior femoral condyle, creating a medial pivot system, and applying a single radius system on the femoral component. Whereas, the tibial insert component could be designed by setting up the posterior tibial slope, and creating a post-cam stabilizer mechanism. Many knowledge gaps related to the population of research objects, lack of research on extreme angles, development of TKA components, are discussed. Further needs of extensive research on TKA in Mongoloid races are anticipated to be introduced for extreme angles and most comprehensive product development for optimization of the flexion angle.
The dose-response relationship between sex hormones and hyperuricemia in different gender: NHANES 2013-2016

Objectives To access the dose-response relationship between sex hormones and hyperuricemia (HUA), and to find the cut-off value in different gender. Methods 9,685 participants were derived from the database of National Health and Nutrition Examination Survey (NHANES). Restricted cubic spline (RCS) analysis were applied to explore the relationship between sex hormones and HUA after adjusting for confounding factors by propensity score match (PSM). Logistic regression was used to estimate the odds ratio (OR) and 95% CI. Results The prevalence of HUA was 15.13% in female participants and 22.30% in male participants. Logistic regression analysis showed that estradiol (E2) was independently associated with HUA for a P value of 0.003 and 0.01in female and male participants, respectively. Testosterone (T) was only independently associated with HUA in male participants (P<0.001) but not in female participants (P = 0.59). RCS analysis showed a dose-response relationship between sex hormones and HUA. The risk of HUA increased as E2 lower than 29.6pg/mL in female participants and T lower than 389.1ng/dL in male participants. E2 higher than 23.6pg/ml was an independent risk factor for HUA in male participants. Conclusion A dose-response relationship was found between sex hormones and HUA. The cut-off value of E2 in male and female participants was 29.6pg/mL and 23.6pg/mL, respectively, and the cut-off value of T in male participants was 389.1ng/dL. These results provide a reference for preventing HUA and hormone supplement therapy.