Mitochondrial ferritin attenuates cerebral ischaemia/reperfusion injury by inhibiting ferroptosis

Ischaemic stroke is becoming the most common cerebral disease in aging populations, but the underlying molecular mechanism of the disease has not yet been fully elucidated. Increasing evidence has indicated that an excess of iron contributes to brain damage in cerebral ischaemia/reperfusion (I/R) injury. Although mitochondrial ferritin (FtMt) plays a critical role in iron homeostasis, the molecular function of FtMt in I/R remains unknown. We herein report that FtMt levels are upregulated in the ischaemic brains of mice. Mice lacking FtMt experience more severe brain damage and neurological deficits, accompanied by typical molecular features of ferroptosis, including increased lipid peroxidation and disturbed glutathione (GSH) after cerebral I/R. Conversely, FtMt overexpression reverses these changes. Further investigation shows that Ftmt ablation promotes I/R-induced inflammation and hepcidin-mediated decreases in ferroportin1, thus markedly increasing total and chelatable iron. The elevated iron consequently facilitates ferroptosis in the brain of I/R. In brief, our results provide evidence that FtMt plays a critical role in protecting against cerebral I/R-induced ferroptosis and subsequent brain damage, thus providing a new potential target for the treatment/prevention of ischaemic stroke

Mitochondrial Ferritin Deletion Exacerbates β

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein which protects mitochondria from iron-induced oxidative damage. Our previous studies indicate that FtMt attenuates β-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on β-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and Ftmt knockout mice were infused intracerebroventricularly (ICV) with Aβ25–35 to establish an Alzheimer’s disease model. Knockout of Ftmt significantly exacerbated Aβ25–35-induced learning and memory impairment. The Bcl-2/Bax ratio in mouse hippocampi was decreased and the levels of cleaved caspase-3 and PARP were increased. The number of neuronal cells undergoing apoptosis in the hippocampus was also increased in Ftmt knockout mice. In addition, the levels of L-ferritin and FPN1 in the hippocampus were raised, and the expression of TfR1 was decreased. Increased MDA levels were also detected in Ftmt knockout mice treated with Aβ25–35. In conclusion, this study demonstrated that the neurological impairment induced by Aβ25–35 was exacerbated in Ftmt knockout mice and that this may relate to increased levels of oxidative stress

Plasma Lipidomics Profiling Reveals Biomarkers for Papillary Thyroid Cancer Diagnosis

The objective of this study was to identify potential biomarkers and possible metabolic pathways of malignant and benign thyroid nodules through lipidomics study. A total of 47 papillary thyroid carcinomas (PTC) and 33 control check (CK) were enrolled. Plasma samples were collected for UPLC-Q-TOF MS system detection, and then OPLS-DA model was used to identify differential metabolites. Based on classical statistical methods and machine learning, potential biomarkers were characterized and related metabolic pathways were identified. According to the metabolic spectrum, 13 metabolites were identified between PTC group and CK group, and a total of five metabolites were obtained after further screening. Its metabolic pathways were involved in glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, Phosphatidylinositol signaling system and the metabolism of arachidonic acid metabolism. The metabolomics method based on PROTON nuclear magnetic resonance (NMR) had great potential for distinguishing normal subjects from PTC. GlcCer(d14:1/24:1), PE-NME (18:1/18:1), SM(d16:1/24:1), SM(d18:1/15:0), and SM(d18:1/16:1) can be used as potential serum markers for the diagnosis of PTC

Compressive Behavior of Bamboo Sheet Twining Tube-Confined Concrete Columns

This study experimentally investigated various axial compressive parameters of a new type of confined concrete, which is termed bamboo sheet twining tube-confined concrete (BSTCC). This new composite structure was composed of an outer bamboo composite tube (BCT) jacket and a concrete core. Under axial compression, the parameters of thirty-six specimens include concrete strength (i.e., C30 and C50) and BCT thickness (i.e., 6, 12, 18, 24, and 30 layers). The mechanical properties of the BSTCC specimens from the perspective of the failure mode, stress-strain relationship, effect of BCT thickness and dilation behavior were analyzed. The results showed that, in compression, with an increase in BCT thickness in the range of 18-layers of bamboo sheets, the strength increased remarkably. When the strength of the concrete core was high, the confinement effect of the BCT was reduced. In addition, the BCT thickness relieved the dilation of the BSTCC specimens. Finally, the experimental results were compared with predictions obtained from 7 existing FRP-confined concrete models. All the predictions had good agreement with the test results, which further confirmed that the models developed for FRP-confined concrete can provide an acceptable approximation of the ultimate strength of the BSTCC specimens

Dispersion Equation of the Coaxial-Radial Line

Abstract An all-metal slow-wave structure, coaxial-radial line, which is suitable for application in broadband high power traveling wave tube (TWT) and relativistic TWT as a RF system is introduced. Making use of the field matching method and variational method together with the orthogonality of the Bessel function and the Floquet Theroem for the periodic system, the dispersion characteristic expression is derived. This equation is more rigorous than that of precious reports

Influence of the Cross-Sectional Shape and Corner Radius on the Compressive Behaviour of Concrete Columns Confined by FRP and Stirrups

Axial compression tests were carried out on 72 FRP (fiber reinforced polymer)–stirrup composite-confined concrete columns. Stirrups ensure the residual bearing capacity and ductility after the FRP fractures. To reduce the effect of stress concentration at the corners of the confined square-section concrete columns and improve the restraint effect, an FRP–stirrup composite-confined concrete structure with rounded corners is proposed. Different corner radii of the stirrup and outer FRP were designed, and the corner radius of the stirrup was adjusted accurately to meet the designed corner radius of the outer FRP. The cross-section of the specimens gradually changed from square to circular as the corner radius increased. The influence of the cross-sectional shape and corner radius on the compressive behaviour of FRP–stirrup composite-confined concrete was analysed. An increase in the corner radius can cause the strain distribution of the FRP to be more uniform and strengthen the restraint effect. The larger the corner radius of the specimen, the better the improvement of mechanical properties. The strength of the circular section specimen was greatly improved. In addition, the test parameters also included the FRP layers, FRP types and stirrup spacing. With the same corner radius, increasing the number of FRP layers or densifying the stirrup spacing effectively improved the mechanical properties of the specimens. Finally, a database of FRP–stirrup composite-confined concrete column test results with different corner radii was established. The general calculation models were proposed, respectively, for the peak points, ultimate points and stress–strain models that are applicable to FRP-, stirrup- and FRP–stirrup-confined concrete columns with different cross-sectional shapes under axial compression

Design and Fabrication of a Slanted-Beam MEMS Accelerometer

This paper presents a novel capacitive microelectromechanical systems (MEMS) accelerometer with slanted supporting beams and all-silicon sandwich structure. Its sensing mechanism is quite similar to an ordinary sandwich-type MEMS accelerometer, except that its proof mass is suspended by a beam parallel to the {111} plane of a (100) silicon wafer. In this way, each sensing element can detect accelerations in two orthogonal directions. Four of these sensing elements could work together and constitute a 3-axis micro-accelerometer by using a simple planar assembly process. This design avoids the traditional 3-axis accelerometer’ disadvantage of possible placement inaccuracy when assembling on three different planes and largely reduces the package volume. The slanted-beam accelerometer’s performance was modeled and analyzed by using both analytical calculations and finite element method (FEM) simulations. A prototype of one sensing element was fabricated and tested. Measured results show that this accelerometer has a good bias stability 76.8 ppm (1σ, tested immediately after power on), two directional sensitivities (sensitivity angle α = 45.4°) and low nonlinearity (<0.5%) over a sensing range up to ±50 g, which demonstrates a great opportunity for future high-precision three-axis inertial measurement

Reversibly Migratable Fluorescent Probe for Precise and Dynamic Evaluation of Cell Mitochondrial Membrane Potentials

The mitochondrial membrane potential (MMP, ΔΨmito) provides the charge gradient required for mitochondrial functions and is a key indicator of cellular health. The changes in MMP are closely related to diseases and the monitoring of MMP is thus vital for pathological study and drug development. However, most of the current fluorescent probes for MMP rely solely on the cell fluorescence intensity and are thus restricted by poor photostability, rendering them not suitable for long-term dynamic monitoring of MMP. Herein, an MMP-responsive fluorescent probe pyrrolyl quinolinium (PQ) which is capable of reversible migration between mitochondria and nucleolus is developed and demonstrated for dynamic evaluation of MMP. The fluorescence of PQ translocates from mitochondria to nucleoli when MMP decreases due to the intrinsic RNA-specificity and more importantly, the translocation is reversible. The cytoplasm to nucleolus fluorescence intensity ratio is positively correlated with MMP so that this method avoids the negative influence of photostability and imaging parameters. Various situations of MMP can be monitored in real time even without controls. Additionally, long-term dynamic evaluation of MMP is demonstrated for HeLa cells using PQ in oxidative environment. This study is expected to give impetus to the development of mitochondria-related disease diagnosis and drug screening

Unilateral Biportal Endoscopic Laminectomy for Treating Cervical Stenosis: A Technical Note and Preliminary Results

Objective: The objective of this study was to introduce a surgical technique for the percutaneous decompression of cervical stenosis (CS) using a unilateral biportal endoscopic approach and characterize its early clinical and radiographic results. Materials and Methods: Nineteen consecutive patients with CS who needed surgical intervention were recruited. All enrolled patients underwent unilateral biportal endoscopic laminectomy (UBEL). All patients were followed postoperatively for >1 year. The preoperative and final follow-up evaluations included the Japanese Orthopedic Association (JOA) score for neurological assessment, visual analogue scale (VAS) for axial pain and C2–C7 Cobb angle for cervical sagittal alignment. The postoperative complications were analyzed. Results: Thirteen males and six females were included in the analysis. The mean follow-up period was 16.3 ± 2.6 months. The mean operative time was 82.6 ± 18.4 min. Postoperative MRI and CT revealed ideal neural decompression of the treated segments in all patients. Preoperative VAS and JOA scores improved significantly after the surgery, and cervical lordosis was preserved on the postoperative images. Conclusions: UBEL was an effective surgical method for CS, which may also minimize iatrogenic damage to the posterior tension band (PTB) and help to maximize the preservation of the cervical lordosis