DataSheet2_Identification of a novel m5C/m6A-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.docx

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer (NSCLC) and is associated with high mortality rates. However, effective methods to guide clinical therapeutic strategies for LUAD are still lacking. The goals of this study were to analyze the relationship between an m5C/m6A-related signature and LUAD and construct a novel model for evaluating prognosis and predicting drug resistance and immunotherapy efficacy. We obtained data from LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Based on the differentially expressed m5C/m6A-related genes, we identified distinct m5C/m6A-related modification subtypes in LUAD by unsupervised clustering and compared the differences in functions and pathways between different clusters. In addition, a risk model was constructed using multivariate Cox regression analysis based on prognostic m5C/m6A-related genes to predict prognosis and immunotherapy response. We showed the landscape of 36 m5C/m6A regulators in TCGA-LUAD samples and identified 29 differentially expressed m5C/m6A regulators between the normal and LUAD groups. Two m5C/m6A-related subtypes were identified in 29 genes. Compared to cluster 2, cluster 1 had lower m5C/m6A regulator expression, higher OS (overall survival), higher immune activity, and an abundance of infiltrating immune cells. Four m5C/m6A-related gene signatures consisting of HNRNPA2B1, IGF2BP2, NSUN4, and ALYREF were used to construct a prognostic risk model, and the high-risk group had a worse prognosis, higher immune checkpoint expression, and tumor mutational burden (TMB). In patients treated with immunotherapy, samples with high-risk scores had higher expression of immune checkpoint genes and better immunotherapeutic efficacy than those with low-risk scores. We concluded that the m5C/m6A regulator-related risk model could serve as an effective prognostic biomarker and predict the therapeutic sensitivity of chemotherapy and immunotherapy.</p

Image2_Identification of a novel m5C/m6A-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.TIF

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer (NSCLC) and is associated with high mortality rates. However, effective methods to guide clinical therapeutic strategies for LUAD are still lacking. The goals of this study were to analyze the relationship between an m5C/m6A-related signature and LUAD and construct a novel model for evaluating prognosis and predicting drug resistance and immunotherapy efficacy. We obtained data from LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Based on the differentially expressed m5C/m6A-related genes, we identified distinct m5C/m6A-related modification subtypes in LUAD by unsupervised clustering and compared the differences in functions and pathways between different clusters. In addition, a risk model was constructed using multivariate Cox regression analysis based on prognostic m5C/m6A-related genes to predict prognosis and immunotherapy response. We showed the landscape of 36 m5C/m6A regulators in TCGA-LUAD samples and identified 29 differentially expressed m5C/m6A regulators between the normal and LUAD groups. Two m5C/m6A-related subtypes were identified in 29 genes. Compared to cluster 2, cluster 1 had lower m5C/m6A regulator expression, higher OS (overall survival), higher immune activity, and an abundance of infiltrating immune cells. Four m5C/m6A-related gene signatures consisting of HNRNPA2B1, IGF2BP2, NSUN4, and ALYREF were used to construct a prognostic risk model, and the high-risk group had a worse prognosis, higher immune checkpoint expression, and tumor mutational burden (TMB). In patients treated with immunotherapy, samples with high-risk scores had higher expression of immune checkpoint genes and better immunotherapeutic efficacy than those with low-risk scores. We concluded that the m5C/m6A regulator-related risk model could serve as an effective prognostic biomarker and predict the therapeutic sensitivity of chemotherapy and immunotherapy.</p

Transfer learning‐based surrogate‐assisted design optimisation of a five‐phase magnet‐shaping PMSM

 Multi-phase permanent-magnet synchronous machines (MPMSMs) with high reliability due to sufficient fault-tolerant capability have considerable potential for transportation electrification applications. Here, an efficient surrogate-assisted design optimisation method is proposed based on analytical model transfer learning for torque characteristic optimisation of a five-phase magnet-shaping PMSM. By employing transfer learning of the source domain analytical model data and the target domain finite element analysis (FEA) data in surrogate model training, the proposed method can achieve both high accuracy and high efficiency from the merits of FEA- and analytical-based optimisations, respectively. The studied machine with five-phases and harmonic injected surface-mounted PMs to enable harmonic injection for torque capability improvement is introduced and the analytical model is built based on the segmented PM and the complex conformal mapping methods. Besides, the optimal Latin hypercube design (LHD) and Taguchi methods are used to form the source and target domain datasets, respectively, so that data features can be efficiently captured over a wide range of optimisation variables. An optimal design is obtained by multi-objective optimisation using the trained surrogate model, which is prototyped and measured to validate the proposed method. </p

A Description of Enzymatic Catalysis in <i>N</i>‑Acetylhexosamine 1‑Kinase: Concerted Mechanism of Two-Magnesium-Ion-Assisted GlcNAc Phosphorylation, Flexibility Behavior of Lid Motif upon Substrate Recognition, and Water-Assisted GlcNAc-1‑P Release

The <i>N</i>-acetylhexosamine 1-kinase (NahK) is the typical example of anomeric kinases acting on gluco-type substrate, which catalyzes the phosphorylation of GlcNAc or GalNAc at anomeric C1 position with ATP, playing a crucial role in bifidobacteria metabolic pathway and biosynthesis of sugar 1-phosphates and oligosaccharides. Herein, by using state-of-the art ab initio QM/MM MD and MM MD simulations, one-dimensional and two-dimensional free energy profiles to descript catalytic process have been explored. A concerted mechanism has been recognized for the delivery of phosphate group and proton to product ADP and GlcNAc-1-P with the free energy barrier of ∼7.0 kcal/mol. The chemical reaction is assisted by two Mg²⁺ ions with a standing six coordination structure during the enzymatic process. The deficiency of Mg²⁺ bridging β–γ phosphates of ATP may alter the catalytic mechanism and brings higher free energy barriers. The protonation of GlcNAc-1-P is beneficial because its eliminates the Mg²⁺ ion binding. The water-assisted GlcNAc-1-P cleavage from binding of Mg²⁺ requires ∼9.4 kcal/mol at least, which means that the π–π bond breaking in the chemical reaction step is probably not the rate-limiting step in the entire enzymatic process. A strongly exothermic phenomenon and an open-closed structural change of lid motif have been observed upon the GlcNAc binding. The exothermic trend is strongly dependent on the quantity and quality of the hydrogen bond network around the ligand

Electromagnetic Design of Ultra-high Efficiency Permanent Magnet Machines with Integrated Drives

This paper investigates the electromagnetic design of an ultra-high efficiency interior permanent magnet synchronous machine with integrated drive system combining power-electronic inverters achieving higher efficiency rate than the currently highest IE5 premium high efficiency standard at the rated operation condition. The design concepts of a standard 55kW industrial motor driven system have been given firstly. Then, the topology and design parameters including slot-pole combinations, winding layouts, and rotor structure have been given after design optimization. The electromagnetic performance of the final optimal machine design has been analyzed, which validate the potential of proposed machine design to reach “IE8” efficiency standard.</p

Individual risk of bias and quality assessment using SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation).

Individual risk of bias and quality assessment using SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation).</p

Forest plot on the expression of IL4 in decidual tissue between the experimental group and control group.

Forest plot on the expression of IL4 in decidual tissue between the experimental group and control group.</p

Forest plots for the effects in different cite of injection cells on IL4 from decidual tissue.

Forest plots for the effects in different cite of injection cells on IL4 from decidual tissue.</p

Forest plot on the expression of IFN-γ from decidual tissue between the experimental group and control group.

Forest plot on the expression of IFN-γ from decidual tissue between the experimental group and control group.</p

Subgroup analysis of MSC treatment effects on the expression of IFN-γ from decidual tissue.

Subgroup analysis of MSC treatment effects on the expression of IFN-γ from decidual tissue.</p