Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg ...effect plays a crucial role in non‐tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β‐mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non‐tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non‐tumor diseases.
Warburg effect plays a crucial role in non‐tumor diseases. This review focuses on the newest researches about the role of Warburg effect in non‐tumor diseases, including pulmonary hypertension, tuberculosis, idiopathic pulmonary fibrosis, failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and polycystic kidney disease. Obviously, Warburg effect may be a potential therapeutic target for those non‐tumor diseases.
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in ...various diseases through different signal pathways. In this review, we discuss the possible mechan- isms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase （PI3K）/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion （I/R） injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointes- tinal diseases. Apelin/APJ system decreases myocardial infarction size and alleviates myocardial I/R injury by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system plays a poten- tial physiological role in gastrointestinal cytoprotection by regulating apoptosis. We hope that a bet- ter understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases.
Excess iron accumulation and cardiac oxidative stress have been shown as important mediators of cardiac hypertrophy, whereas it remains largely elusive about the occurrence of mitochondrial iron ...overload and its significance during cardiac hypertrophy. In the present study, we aim to investigate the role of NCOA4-mediated ferritinophagy and SFXN1-dependent mitochondria iron overload in apelin-13-induced cardiomyocytes hypertrophy. Apelin-13 significantly promotes ferric citrate (FAC)-induced total cellular and mitochondria ion production, as well as mitochondria ROS contents. Mechanistically, apelin-13 effectively induces the expression of SFXN1, a mitochondria iron transporting protein and NCOA4, a cargo receptor of ferritinophagy in dose and time-dependent manner. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. In addition, apelin-13-triggered mitochondria iron overload is reversed by the genetic inhibition of SFXN1 and NCOA4. NCOA4 deficiency via its silencing also interferes with the enhanced expression of SFXN1 evoked by apelin-13. In apelin-13-treated H9c2 cells, the promotion in cell diameter, volume as well as protein contents are obviously suppressed by the knockdown of NCOA4 and SFXN1 with their corresponding siRNAs. Remarkably, the human and murine hypertrophic hearts models, as well as apelin-13-injected mice models, present evident cardiac mitochondrial iron deposition and raised expressions of NCOA4 and SFXN1. Taken together, these results provide experimental evidences that NCOA4-mediated ferritinophagy might be defined as an essential mechanism leading to apelin-13-cardiomyocytes hypertrophy in SFXN1-dependent mitochondria iron overload manners.
•NCOA4-mediated ferritinophagy is indispensable for apelin-13-cardiomyocytes hypertrophy.•Apelin-13-induced cardiomyocyte hypertrophy is attributed to SFXN1-linked to mitochondria iron overload•Ferritinophagy activation and SFXN1-regulated mitochondria iron transporting are essential for cardiomyocytes hypertrophy.
Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as ...a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity (FC). A longitudinal design was adopted to investigate the alteration in FC dynamics using a dynamic functional connectivity (dFC) approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation (rTMS) with the target at the left dorsolateral prefrontal cortex (DLPFC). Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs (TSZ,
n
= 27), while the other group only received antipsychotic drugs (DSZ,
n
= 26). Resting-state functional magnetic resonance imaging (fMRI) and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline (
t1
) and after 4-week treatment (
t2
). The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit (CTCC). For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression (SVR) results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS.
The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for ...potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a potential target in cancer treatment. We firstly utilize molecular dynamic (MD) simulation to rationally design and screen serial peptide-Au cluster compounds with special peptide sequences and precise gold atoms, which can recognize and bind specific domain of GPx-1 with high affinity. The theoretical simulations were further verified by the following peptide-Au clusters synthesis and GPx-1 activity suppression studies in buffer and cells, respectively. Further cytological experiments corroborated that peptide-Au clusters are promising nanoparticles inducing tumor cells apoptosis by suppressing GPx-1 activity and increasing higher cellular reactive oxygen species level to initiate tumor cell apoptosis through intrinsic mitochondrial pathway.
In this paper, the dynamics of cantilevered flexible plates subjected to axial flow is investigated theoretically and experimentally. A nonlinear equation of motion of the plate based on the ...inextensibility assumption, coupled with an unsteady lumped vortex model for the aerodynamic part is used to analyze the instability and post-critical dynamical behaviour of this fluid–structure system theoretically. Experiments have been conducted in a 3
ft×2
ft (914
mm×610
mm) cross-section wind tunnel, using polypropylene carbonate (PPC) films, thin brass plates, polyethylene terephthalate (PET) sheets, and type 304 stainless steel sheets, with maximum dimensions 224
mm×168
mm. In the experiments, time traces, power spectral densities (PSDs), phase-plane plots, Poincaré maps, probability density functions (PDFs) and autocorrelations are used to characterize the motions of the system.
Periodic and chaotic oscillations have been observed in the experiments. It has also been observed that flutter arises via a subcritical bifurcation involving hysteresis for large aspect ratio plates; this hysteresis does not occur for low aspect ratio plates. The hysteresis phenomenon is considered to be due to spanwise deformation of the plates. The effect of aspect ratio on critical flow velocity is investigated. The experimental critical flow velocities for flutter onset are in good agreement with the theoretically predicted values.
► Dynamics of the FSI system is investigated theoretically and experimentally. ► Cantilevered plates suffer a Hopf bifurcation, LCOs and chaotic oscillations. ► Hysteresis phenomenon is observed in experiments with large aspect ratio plates. ► 3-D flow and 3-D deformations of plate have effect on critical flow velocity. ► Dependence of the critical flow velocity on the plate length is investigated.
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a zoonotic pathogen, has led to the outbreak of coronavirus disease 2019 (COVID-19) pandemic and brought ...serious threats to public health worldwide. The gold standard method for SARS-CoV-2 detection requires both reverse transcription (RT) of the virus RNA to cDNA and then polymerase chain reaction (PCR) for the cDNA amplification, which involves multiple enzymes, multiple reactions and a complicated assay optimization process. Here, we developed a duplex-specific nuclease (DSN)-based signal amplification method for SARS-CoV-2 detection directly from the virus RNA utilizing two specific DNA probes. These specific DNA probes can hybridize to the target RNA at different locations in the nucleocapsid protein gene (N gene) of SARS-CoV-2 to form a DNA/RNA heteroduplex. DSN cleaves the DNA probe to release fluorescence, while leaving the RNA strand intact to be bound to another available probe molecule for further cleavage and fluorescent signal amplification. The optimized DSN amount, incubation temperature and incubation time were investigated in this work. Proof-of-principle SARS-CoV-2 detection was demonstrated with a detection sensitivity of 500 pM virus RNA. This simple, rapid, and direct RNA detection method is expected to provide a complementary method for the detection of viruses mutated at the PCR primer-binding regions for a more precise detection.
Real-time pH control on-chip is a crucial factor for cell-based experiments in microfluidics, yet difficult to realize. In this paper, we present a flexible pH regulator on a digital microfluidic ...(DMF) platform. The pico-dosing technology, which can generate and transfer satellite droplets, is presented to deliver alkali/acid into the sample solution to change the pH value of the sample. An image analysis method based on ImageJ is developed to calculate the delivered volume and an on-chip colorimetric method is proposed to determine the pH value of the sample solution containing the acid-base indicator. The calculated pH values show consistency with the measured ones. Our approach makes the real-time pH control of the on-chip biological experiment more easy to control and flexible.
Conclusion: The shape from shading and optical flow are implemented to three-dimensional (3D) reconstruction.
Objective: Solve the problem of 3D reconstruction in endoscope imaging.
Method: One of ...the fundamental approaches in the domain of computer vision is shape from shading. This algorithm was proposed to obtain the shape of an object from a single intensity image. Because of the severe conditions are required in shape from shading to reconstruct 3D surface. The photometric calibration is proposed from the view of image processing. The calibration is important for illumination-based visualization techniques such as SFS (shape-from-shading). However, the surface reconstruction from SFS is the relative variation in the grey gradient field. So the change from relative variation to absolute variation is necessary when the actual size of surroundings has to be known. Then the optical flow is introduced to solve this change in the paper. The optical tracker is also used in this system to capture the pose of endoscopy.
Result: The stability of surface reconstruction is improved when the photometric calibration is used before shape from shading.
New MDS Euclidean Self-Orthogonal Codes Fang, Xiaolei; Liu, Meiqing; Luo, Jinquan
IEEE transactions on information theory,
2021-Jan., 2021-1-00, Volume:
67, Issue:
1
Journal Article
Peer reviewed
Open access
In this paper, two criterions of MDS Euclidean self-orthogonal codes are presented. New MDS Euclidean self-dual codes and self-orthogonal codes are constructed via the criterions. In particular, ...among our constructions, for large square <inline-formula> <tex-math notation="LaTeX">q </tex-math></inline-formula>, about <inline-formula> <tex-math notation="LaTeX">\frac {1}{8}\cdot q </tex-math></inline-formula> new MDS Euclidean (almost) self-dual codes over <inline-formula> <tex-math notation="LaTeX"> \mathbb {F}_{q} </tex-math></inline-formula> can be produced. Moreover, we can construct about <inline-formula> <tex-math notation="LaTeX">\frac {1}{4}\cdot q </tex-math></inline-formula> new MDS Euclidean self-orthogonal codes with different even lengths <inline-formula> <tex-math notation="LaTeX">n </tex-math></inline-formula> and dimension <inline-formula> <tex-math notation="LaTeX">\frac {n}{2}-1 </tex-math></inline-formula>.
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