BCL2L13 promotes mitophagy through DNM1L-mediated mitochondrial fission in glioblastoma

There is an urgent need for novel diagnostic and therapeutic strategies for patients with Glioblastoma multiforme (GBM). Previous studies have shown that BCL2 like 13 (BCL2L13) is a member of the BCL2 family regulating cell growth and apoptosis in different types of tumors. However, the clinical significance, biological role, and potential mechanism in GBM remain unexplored. In this study, we showed that BCL2L13 expression is significantly upregulated in GBM cell lines and clinical GBM tissue samples. Mechanistically, BCL2L13 targeted DNM1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux. Functionally, these alterations significantly promoted the proliferation and invasion of GBM cells both in vitro and in vivo. Overall, our findings demonstrated that BCL2L13 plays a significant role in promoting mitophagy via DNM1L-mediated mitochondrial fission in GBM. Therefore, the regulation and biological function of BCL2L13 render it a candidate molecular target for treating GBM.publishedVersio

Nicotinamide Riboside and Metformin Ameliorate Mitophagy Defect in Induced Pluripotent Stem Cell-Derived Astrocytes With POLG Mutations

Mitophagy specifically recognizes and removes damaged or superfluous mitochondria to maintain mitochondrial homeostasis and proper neuronal function. Defective mitophagy and the resulting accumulation of damaged mitochondria occur in several neurodegenerative diseases. Previously, we showed mitochondrial dysfunction in astrocytes with POLG mutations, and here, we examined how POLG mutations affect mitophagy in astrocytes and how this can be ameliorated pharmacologically. Using induced pluripotent stem cell (iPSC)-derived astrocytes carrying POLG mutations, we found downregulation of mitophagy/autophagy-related genes using RNA sequencing-based KEGG metabolic pathway analysis. We confirmed a deficit in mitochondrial autophagosome formation under exogenous stress conditions and downregulation of the mitophagy receptor p62, reduced lipidation of LC3B-II, and decreased expression of lysosome protein lysosomal-associated membrane protein 2A (LAMP2A). These changes were regulated by the PINK1/Parkin pathway and AKT/mTOR/AMPK/ULK1 signaling pathways. Importantly, we found that double treatment with nicotinamide riboside (NR) and metformin rescued mitophagy defects and mitochondrial dysfunction in POLG-mutant astrocytes. Our findings reveal that impaired mitophagy is involved in the observed mitochondrial dysfunction caused by POLG mutations in astrocytes, potentially contributing to the phenotype in POLG-related diseases. This study also demonstrates the therapeutic potential of NR and metformin in these incurable mitochondrial diseases.publishedVersio

Magnetic and Cryogenic Design of the MICE Coupling Solenoid Magnet System

The Muon Ionization Cooling Experiment (MICE) will demonstrate ionization cooling in a short section of a realistic cooling channel using a muon beam at Rutherford Appleton Laboratory in the UK. The coupling magnet is a superconducting solenoid mounted around four 201MHz RF cavities, which produces magnetic field up to 2.6 T on the magnet centerline to keep muons within the iris of RF cavities windows. The coupling coil with inner radius of 750mm, length of 285mm and thickness of 102.5mm will be cooled by a pair of 1.5 W at 4.2 K small coolers. This paper will introduce the updated engineering design of the coupling magnet made by ICST in China. The detailed analyses on magnetic fields, stresses induced during the processes of winding, cool down and charging, and cold mass support assembly are presented as well

Design and Construction of Test Coils for the MICE Coupling Solenoid Magnet

The superconducting coupling solenoid to be applied in the Muon Ionization Cooling Experiment (MICE) is made from copper matrix Nb-Ti conductors with inner radius of 750 mm, length of 285 mm and thickness of 102.5 mm at room temperature. The magnetic field up to 2.6 T at the magnet centerline is to keep the muons within the MICE RF cavities. Its self inductance is around 592 H and its magnet stored energy is about 13 MJ at a full current of 210 A for the worst operation case of the MICE channel. The stress induced inside the coil during cool down and charging is relatively high. Two test coils are to build and test in order to validate the design method and develop the fabrication technique required for the coupling coil winding, one is 350 mm inner diameter and full length same as the coupling coil, and the other is one-quarter length and 1.5 m diameter. The 1.5 m diameter coil will be charged to strain conditions that are greater than would be encountered in the coupling coil. This paper presents detailed design of the test coils as well as developed winding skills. The analyses on stress in coil assemblies, AC loss, and quench process are carried out

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

IntroductionSafranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.Methods and resultsHere, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.ConclusionThis study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ

Vibration analysis of fluid filled pipework systems

In fluid filled pipework systems there is a need to predict the vibration transmission to the supports or end termination, arising from both variation inputs and fluid pressure inputs. If the vibration transmission was found to be excessive, steps could be taken to vary the stiffness and damping parameters to minimise the total power transmission from the pipe coupling points and the pipe outlet.Pipework systems are quite complex and a few authors have attempted to model them using finite element models or the mobility method both using a modal superposition. The main difficulty is the complexity or overelaboration of these methods. The wave methods have also been used to model fluid filled pipes, but so far are restricted to a straight pipe. The objectives in this thesis are to investigate the theoretical analysis methods, and to develop a computer model for the prediction of the generation and propagation of the dynamic behaviour of three-dimensional complex fluid filled pipework systems.The impedance matrix and transfer matrix methods within the framework of the power flow philosophy have been used to describe five wave types below the ring frequency, namely the three axisymmetric waves (compression and torsional waves in the pipe wall, plane wave in the fluid) and bending waves in two orthogonal axes. Fluid and wall waves are coupled in the radial direction and at discontinuities or pipe bends. The pipework system, described by a 14-element vector of vibration states at a point, is simplified to lumped mass, and stiffness elements for the pipe wall structure, with a longitudinal wave solution for the fluid elements within. The pipe wall elements are chosen to be sufficiently short which is satisfactory for the frequency region of interest. Allowance is made for the fluid loading to both the mass in the structural elements and the wavespeed in the fluid elements. The impedance or mobility of the pipework system is obtained by using the transfer matrix, and gives the transmitted force or power flow of general liquid-filled pipework systems to each point if necessary.</p

Contribution a l'etude des systemes d'elevage mytilicole

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Study on the Coupling Frequency of Double-Sided Submerged Ring-Stiffened Cylindrical Shells

Based on the Flügge theory and orthotropic theory, the acoustic vibration coupling model of ring-stiffened cylindrical shell is established by using the wave propagation method and virtual source method. And the effects of water immersion on both sides, free surface, and hydrostatic pressure on the cylindrical shell are considered in the coupling model. Muller three-point iterative method is used to solve the coupling frequency. The calculation results of degradation theory are compared with COMSOL’s calculation results and experimental results, respectively, which verifies the reliability of the theoretical method. Finally, the influence of fluid load, ring rib parameters, boundary conditions, hydrostatic pressure, and free surface on the coupled vibration of ring-stiffened cylindrical shell is analyzed by an example