Optimization of sub-grid scale model for abrasive flow machining curved tube based on large eddy simulation

Abrasive flow machining technology is a new type of precision machining technology. Due to its unique rheological properties, it can process any complex structure and size parts to meet the requirements that conventional machining cannot meet. Combined with the turbulent flow characteristics of the abrasive flow, the large eddy simulation numerical method is used to simulate the machining process of the abrasive flow. The influence of different sub-grid scale models on the simulation results is discussed. Taking curved tube as the research object, the static pressure, dynamic pressure and velocity of different sub-grid models are analyzed to find the best sub-grid scale model. Large eddy simulation method is used to simulate the complex flow channel parts, and the best sub-grid scale model suitable for complex flow channels is determined, which reveals the grinding and polishing rule of abrasive flow and provides academic support for future research. Therefore, it has frontier and important research value

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Effect of Inotodiol on LPS-induced Injury of RAW264.7 Cells

To explore the effect of Inotolinol (INO) on the inflammatory response of LPS-induced mouse mononuclear macrophages (RAW264.7). The experiment has investigated in vitro the effects of INO on mouse mononuclear macrophages (RAW264.7) induced by LPS. To do this, the following methods were adopted: The viability of RAW264.7 cells was detected by CCK-8 assay. Cell apoptosis was examined by Hoechst33342 and PI. The secretion of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18) and the content of nitric oxide (NO) in cells were measured by ELISA and Griess. The production of reactive oxygen species (ROS), the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in cells were detected by fluorescence probe and kit. The results showed that 20 μmol/L INO could inhibit the decline of RAW264.7 cell viability induced by LPS, prevent cell apoptosis, and significantly inhibit the secretion of IL-6, IL-1β, TNF-α, IL-18 and NO (P<0.01), could significantly reduce the contents of MDA and H2O2 in cells (P<0.01), and could significantly increase the activities of SOD, CAT and GSH in cells (P<0.01). The above results indicate that INO can effectively inhibit the production of pro-inflammatory factors and superoxides induced by LPS in RAW264.7 cells, improve the anti-inflammatory and anti-oxidative abilities of cells, and thus protect cells from damage

RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation

Abstract Neuroblastoma (NB) is a kind of typical life-threatening extracranial tumor in children. N6-methyladenosine (m6A) modification is closely related to multiple cancer pathological processes. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a top-ranked prognostic risk gene in NB; however, its function is uncertain. The expression of m6A-associated enzymes in patients with NB was analyzed using the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The IGF2BP3 level in NB cell lines and primary samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR), western blot method, and immunohistochemical analysis. The IGF2BP3 function in cell proliferation was clarified based on many functional in vitro and in vivo experiments. The interaction between IGF2BP3 and N-myc was researched via RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and chromatin immunoprecipitation (ChIP) assays. The 16 m6A-regulated enzymes in NB were researched, and the result indicated that IGF2BP3 overexpression was related to cancer progression, COG risk, and survival based on the GEO and TARGET databases. Besides, the IGF2BP3 and MYCN levels were positively correlated. IGF2BP3 expression levels increased in MYCN-amplified NB clinical samples and cells. Knockdown of IGF2BP3 inhibited N-myc expression and NB cell proliferation in vitro and in vivo. IGF2BP3 regulates MYCN RNA stability by modifying m6A. In addition, we demonstrated that N-myc is a transcription factor that directly promotes IGF2BP3 expression in NB cells. IGF2BP3 regulates the proliferation of NB cells via m6A modification of MYCN. N-myc also acts as a transcription factor that regulates IGF2BP3 expression. A positive feedback loop between IGF2BP3 and N-myc facilitates NB cell proliferation

Bayesian relative composite quantile regression approach of ordinal latent regression model with L1/2 regularization

Ordinal data frequently occur in various fields such as knowledge level assessment, credit rating, clinical disease diagnosis, and psychological evaluation. The classic models including cumulative logistic regression or probit regression are often used to model such ordinal data. But these modeling approaches conditionally depict the mean characteristic of response variable on a cluster of predictive variables, which often results in non-robust estimation results. As a considerable alternative, composite quantile regression (CQR) approach is usually employed to gain more robust and relatively efficient results. In this paper, we propose a Bayesian CQR modeling approach for ordinal latent regression model. In order to overcome the recognizability problem of the considered model and obtain more robust estimation results, we advocate to using the Bayesian relative CQR approach to estimate regression parameters. Additionally, in regression modeling, it is a highly desirable task to obtain a parsimonious model that retains only important covariates. We incorporate the Bayesian L1/2 penalty into the ordinal latent CQR regression model to simultaneously conduct parameter estimation and variable selection. Finally, the proposed Bayesian relative CQR approach is illustrated by Monte Carlo simulations and a real data application. Simulation results and real data examples show that the suggested Bayesian relative CQR approach has good performance for the ordinal regression models

Anti-Alzheimers molecular mechanism of icariin: insights from gut microbiota, metabolomics, and network pharmacology

Abstract Background Icariin (ICA), an active ingredient extracted from Epimedium species, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate the therapeutic effects and the underlying mechanisms of ICA on AD by an integrated analysis of gut microbiota, metabolomics, and network pharmacology (NP). Methods The cognitive impairment of mice was measured using the Morris Water Maze test and the pathological changes were assessed using hematoxylin and eosin staining. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in the gut microbiota and fecal/serum metabolism. Meanwhile, NP was used to determine the putative molecular regulation mechanism of ICA in AD treatment. Results Our results revealed that ICA intervention significantly improved cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of the APP/PS1 mice. Moreover, the gut microbiota analysis showed that ICA administration reversed AD-induced gut microbiota dysbiosis in APP/PS1 mice by elevating the abundance of Akkermansia and reducing the abundance of Alistipe. Furthermore, the metabolomic analysis revealed that ICA reversed the AD-induced metabolic disorder via regulating the glycerophospholipid and sphingolipid metabolism, and correlation analysis revealed that glycerophospholipid and sphingolipid were closely related to Alistipe and Akkermansia. Moreover, NP indicated that ICA might regulate the sphingolipid signaling pathway via the PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for the treatment of AD. Conclusion These findings indicated that ICA may serve as a promising therapeutic approach for AD and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder. Graphical Abstrac