Mammalian target of rapamycin (mTOR) is a major downstream effector of the receptor tyrosine kinase (RTK)-phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homologue 1 (AKT) signaling pathway. Although this signaling network is frequently altered in cancer, the underlying mechanisms that cause tumorigenesis as a result of activated mTOR remain largely unknown. We report here that expression of lactate dehydrogenase B (LDHB), a critical enzymatic activator of glycolysis, was upregulated in an mTOR-dependent manner in TSC1

Comprehensive assessment of serum lipidomic aberrations before type 2 diabetes mellitus (T2DM) onset has remained lacking in Han Chinese. We evaluated changes in lipid coregulation antecedent to T2DM and identified novel lipid predictors for T2DM in individuals with normal glucose regulation (NGR). RESEARCH DESIGN AND METHODSIn the discovery study, we tested 667 baseline serum lipids in subjects with incident diabetes and propensity score-matched control subjects (n = 200) from a prospective cohort comprising 3,821 Chinese adults with NGR. In the validation study, we tested 250 lipids in subjects with incident diabetes and matched control subjects (n = 724) from a pooled validation cohort of 14,651 individuals with NGR covering five geographical regions across China. Differential correlation network analyses revealed perturbed lipid coregulation antecedent to diabetes. The predictive value of a serum lipid panel independent of serum triglycerides and 2-h postload glucose was also evaluated. RESULTSAt the level of false-discovery rate <0.05, 38 lipids, including triacylglycerols (TAGs), lyso-phosphatidylinositols, phosphatidylcholines, polyunsaturated fatty acid (PUFA)-plasmalogen phosphatidylethanolamines (PUFA-PEps), and cholesteryl esters, were significantly associated with T2DM risk in the discovery and validation cohorts. A preliminary study found most of the lipid predictors were also significantly associated with the risk of prediabetes. Differential correlation network analysis revealed that perturbations in intraclass (i.e., non-PUFA-TAG and PUFA-TAGs) and interclass (i.e., TAGs and PUFA-PEps) lipid coregulation preexisted before diabetes onset. Our lipid panel further improved prediction of incident diabetes over conventional clinical indices. CONCLUSIONSThese findings revealed novel changes in lipid coregulation existing before diabetes onset and expanded the current panel of serum lipid predictors for T2DM in normoglycemic Chinese individuals.

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In the last few decades, numerical simulation for nonlinear oscillators has received a great deal of attention, and many researchers have been concerned with the design and analysis of numerical methods for solving oscillatory problems. In this paper, from the perspective of the continuous finite element method, we propose and analyze new energy-preserving functionally fitted methods, in particular trigonometrically fitted methods of an arbitrarily high order for solving oscillatory nonlinear Hamiltonian systems with a fixed frequency. To implement these new methods in a widespread way, they are transformed into a class of continuous-stage Runge-Kutta methods. This paper is accompanied by numerical experiments on oscillatory Hamiltonian systems such as the FPU problem and nonlinear Schrödinger equation. The numerical results demonstrate the remarkable accuracy and efficiency of our new methods compared with the existing high-order energy-preserving methods in the literature.