Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing.

Lithocholic acid (LCA) is accumulated in mammals during calorie restriction and it can activate AMP-activated protein kinase (AMPK) to slow down ageing. However, the molecular details of how LCA activates AMPK and induces these biological effects are unclear. Here we show that LCA enhances the activity of sirtuins to deacetylate and subsequently inhibit vacuolar H-ATPase (v-ATPase), which leads to AMPK activation through the lysosomal glucose-sensing pathway.

Efficacy of Astragalus membranaceus-Carthamus tinctorius in cerebral ischemia/reperfusion injury: Insights from metabolomics and mass spectrometry imaging.

Background: The combination of Astragalus membranaceus and Carthamus tinctorius (AC) exhibits significant therapeutic effects in cerebral ischemia/reperfusion injury (CIRI). Understanding the metabolic characteristics of brain microregions and disturbances in tissues and systemic circulation is crucial for elucidating the mechanisms of CIRI and the therapeutic benefits of AC. However, in situ metabolic regulation of the complex brain structure has not been adequately studied, and the therapeutic mechanism of AC requires immediate clarification.

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK.

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose.

Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress.

AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets.

[Pharmacokinetics-pharmacodynamics correlation of protocatechuic aldehyde and hydroxysafflor yellow A alone or their combination use in rats with hyperlipidemia].

To study the pharmacokinetics-pharmacodynamics correlation of protocatechuic aldehyde and hydroxysafflor yellow A alone or their combination use in rats with hyperlipidemia. In this study, the hyperlipidemia model was established by intravenous injection of protocatechuic aldehyde (20 mg•kg⁻¹) and hydroxysafflor yellow A (12 mg•kg⁻¹). The HPLC-DAD method was applied to determine the plasma concentration of protocatechuic aldehyde and hydroxysafflor yellow A at different time points and draw the drug effect-time curve.

Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK.

The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease.

[Study on multi-target optimization of prescription dose of Mahuang decoction].

Objective: To optimize the prescription dose of Mahuang decoction in a multi-target manner, in order to provide reference for the quantitative optimization of the prescription dose of the traditional Chinese medicine compound.

Method: The number of diaphoretic spots in rats, the tracheal antispasmodic rate in guinea pigs and the writhing times by acetic acid in mice were taken as the indexes for evaluating the diaphoretic, antispasmodic and analgesic effects. According to the experimental results of the 16 orthogonal combination prescriptions, a mathematical dose-effect model was built by support vector regression (SVR) and quadratic response surface regression (RSR) respectively.

Chaos of elementary cellular automata rule 42 of Wolfram's class II.

In this paper, the dynamics of elementary cellular automata rule 42 is investigated in the bi-infinite symbolic sequence space. Rule 42, a member of Wolfram's class II which was said to be simply as periodic before, actually defines a chaotic global attractor; that is, rule 42 is topologically mixing on its global attractor and possesses the positive topological entropy. Therefore, rule 42 is chaotic in the sense of both Li-Yorke and Devaney.