Charged Body Research Articles

Relativistic beam loading, recoil-reduction, and residual-wake acceleration with a covariant retarded-potential integrator

An algorithm is demonstrated that performs first-principles tracking of relativistic charged-particles. A covariant approach is used which relies on retarded vector potentials for trajectory integration instead of performing electromagnetic field calculations. When accounting for retardation effects, the peak vector potential and corresponding Lorentz force in the direction of travel increase asymptotically for high-β particles. This produces a very strong field distribution at small angles from the particle’s direction of travel, which can result in considerable change in momentum when approaching a conducting or charged object. We study these dynamics using protons and electrons at relativistic energies passing through apertures in conducting surfaces, where substantial energy shifts are observed for particles passing within roughly 10μm of the aperture boundary.We also simulate breaking a test particle’s line of sight with a conductor or other charged body. After this instant, the test particle continues to accelerate due to residual fields, but no longer produces an opposing force on any charged or conducting object; thus any recoil on the enclosing structure is effectively reduced. In this test, a 1% energy gain is observed for an 85MeV electron traversing its reflected wake after having conducting plate in its path screened by a dielectric object.We then incorporate a micro-scale dielectric laser acceleration (DLA) device into our simulations. Compared with a 2 mm DLA on its own, we find a factor of two increase in energy gain when adding a series of conducting-surface choppers.

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.

Micronuclear collapse from oxidative damage.

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood. In this study, we found that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function of charged multivesicular body protein 7 (CHMP7), a scaffolding protein for the membrane repair complex known as endosomal sorting complex required for transport III (ESCRT-III). ROS retained CHMP7 in micronuclei while disrupting its interaction with other ESCRT-III components. ROS-induced cysteine oxidation stimulated CHMP7 oligomerization and binding to the nuclear membrane protein LEMD2, disrupting micronuclear envelopes. Furthermore, this ROS-CHMP7 pathological axis engendered chromosome shattering known to result from micronuclear rupture. It also mediated micronuclear disintegrity under hypoxic conditions, linking tumor hypoxia with downstream processes driving cancer progression.

Modeling analysis on the influence of the gyrostatic moment on the motion of a charged rigid body subjected to constant axial torque

Modeling analysis on the influence of the gyrostatic moment on the motion of a charged rigid body subjected to constant axial torque

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer

BackgroundProstate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease’s evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear.MethodsIn terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells.ResultsThe expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency.ConclusionsOur findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Functional Insights into the Sphingolipids C1P, S1P, and SPC in Human Fibroblast-like Synoviocytes by Proteomic Analysis.

The (patho)physiological function of the sphingolipids ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC) in articular joints during osteoarthritis (OA) is largely unknown. Therefore, we investigated the influence of these lipids on protein expression by fibroblast-like synoviocytes (FLSs) from OA knees. Cultured human FLSs (n = 7) were treated with 1 of 3 lipid species-C1P, S1P, or SPC-IL-1β, or with vehicle. The expression of individual proteins was determined by tandem mass tag peptide labeling followed by high-resolution electrospray ionization (ESI) mass spectrometry after liquid chromatographic separation (LC-MS/MS/MS). The mRNA levels of selected proteins were analyzed using RT-PCR. The 3sphingolipids were quantified in the SF of 18 OA patients using LC-MS/MS. A total of 4930 proteins were determined using multiplex MS, of which 136, 9, 1, and 0 were regulated both reproducibly and significantly by IL-1β, C1P, S1P, and SPC, respectively. In the presence of IL-1ß, all 3 sphingolipids exerted ancillary effects. Only low SF levels of C1P and SPC were found. In conclusion, the 3 lipid species regulated proteins that have not been described in OA. Our results indicate that charged multivesicular body protein 1b, metal cation symporter ZIP14, glutamine-fructose-6-P transaminase, metallothionein-1F and -2A, ferritin, and prosaposin are particularly interesting proteins due to their potential to affect inflammatory, anabolic, catabolic, and apoptotic mechanisms.

The asymptotic solutions for the motion of a charged symmetric gyrostat in the irrational frequency case

The primary objective of this study is to explore the spatial rotary movements of a symmetrically charged rigid body (RB) that is rotating around a fixed point, akin to Lagrange’s scenario as a novel scenario where its center of mass experiences a slight displacement from the symmetry dynamic axis. The body’s movement is presumed to be affected by a gyrostatic moment and a force from an electromagnetic field, attributed to the presence of a located point charge on this axis. The regulating equations of motion that are pertaining to the equations Euler–Poisson are solved through the utilization of Poincaré’s small parameter method along with its adaptations when the scenario of irrational frequencies is considered. The three angles of Euler are derived and graphed to ascertain the body’s position at any point throughout the motion. The temporal evolutions of the achieved outcomes are drawn to showcase the significant impact of the selected parameters on the motion. The phase plane diagrams have been generated to illustrate the stability of the body during the motion. The novelty of studying the rotatory motion of a charged RB under these specific conditions lies in the intricate interplay of gyrostatic effects, magnetic interactions, and nonlinear dynamics. This research can push the boundaries of theoretical mechanics and provide valuable insights and tools for both theoretical advancements and practical applications. Moreover, the achieved results from this analysis can be utilized to improve the dynamic performance of diverse engineering applications, particularly those dependent on gyroscopic theory. This includes enhancing the functionality of satellites, compasses, submarines, and automatic pilots used in aircraft. Essentially, the findings have practical implications for optimizing the performance and stability of these systems.

Evaluating the motion of a charged solid body having a globular cavity

The dynamical motion of a charged symmetrical solid body (SB) about its main symmetric axis is addressed in this work. The body is supposed to have a chamber with a globular shape, in which it contains a mobile mass and filled with a viscous liquid. This mass is assumed to be coupled via a double elastic band at a point that is situated along the dynamical symmetry axis and produces viscous friction. The body’s motion is influenced by a gyrostatic moment (GM), whose first two components on the body’s main axes are chosen to be zero. Additionally, the body is subject to the effects of an electromagnetic field, owing to a located point charge on the body’s dynamic symmetry axis. On the indicated motion, the combined impact of the viscous liquid and the mobile mass is investigated. The achieved outcomes show that, in the presence of internal dissipation, the system's motion tends towards a constant rotation around its axis at the point of highest inertia as time approaches infinity. To demonstrate how the body’s parameters affect the motion, the obtained outcomes are graphed. The method of fourth-order Runge-Kutta (4RKM) is employed to generate the governing system's numerical results, which are then displayed in additional diagrams. This work's relevance is concentrated on its considerable potential for usage in the submarine and gyroscope industries. The novelty of this work lies in the intricate interplay of rotational dynamics due to the GM, viscous liquid and electromagnetic effects to achieve new results, besides the gained numerical outcomes. Therefore, these results are considered novel and have significant theoretical and practical relevance. Moreover, it can be used to study the motion of celestial bodies, such as planets or moons, which might have internal cavities filled with fluids or other materials. The charged nature could be relevant for bodies with significant magnetic fields.

Rotation Matrix of a Charged Symmetrical Body: One-Parameter Family of Solutions in Elementary Functions

Euler–Poisson equations of a charged symmetrical body in external constant and homogeneous electric and magnetic fields are deduced starting from the variational problem, where the body is considered as a system of charged point particles subject to holonomic constraints. The final equations are written for the center-of-mass coordinate, rotation matrix and angular velocity. A general solution to the equations of motion is obtained for the case of a charged ball. For the case of a symmetrical charged body (solenoid), the task of obtaining the general solution is reduced to the problem of a one-dimensional cubic pseudo-oscillator. In addition, we present a one-parametric family of solutions to the problem in elementary functions.

CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model

BackgroundNatural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us...

Analyzing the dynamics of a charged rotating rigid body under constant torques

This study explores the dynamical rotary motion of a charged axisymmetric spinning rigid body (RB) under the effect of a gyrostatic moment (GM). The influence of transverse and invariable body fixed torques (IBFTs), and an electromagnetic force field, is also considered. Euler’s equations of motion (EOM) are utilized to derive the regulating system of motion for the problem in a suitable formulation. Due to the lack of torque exerted along the spin axis and the nearly symmetrical nature of the RB, the spin rate is nearly unchanged. Assuming slight angular deviations of the spin axis relative to a fixed direction in space, it is possible to derive approximate analytical solutions (AS) in closed form for the attitude, translational, and rotational movements. These concise solutions that are expressed in complex form are highly effective in analyzing the maneuvers performed by spinning RBs. The study focuses on deriving the AS for various variables including angular velocities, Euler’s angles, angular momentum, transverse displacements, transverse velocities, axial displacement, and axial velocity. The graphical simulation of the subsequently obtained solutions is presented to show their precision. Furthermore, the positive impacts that alterations in the body’s parameters have on the motion’s behavior are presented graphically. The corresponding phase plane curves, highlighting the influence of different values in relation to the electromagnetic force field, the GM, and the IBFTs are drawn to analyze the stability of the body’s motion. This study has a significant role in various scientific and engineering disciplines. Its importance lies in its ability to optimize mechanical systems, explain celestial motion, and enhance spacecraft performance.

CHMP5 attenuates osteoarthritis via inhibiting chondrocyte apoptosis and extracellular matrix degradation: involvement of NF-κB pathway

BackgroundOsteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear.MethodsIn this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1β) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1β-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays.ResultsDownregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway.ConclusionsThis study demonstrated that CHMP5 repressed IL-1β-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.

Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation.

Objective: To investigate the immune mechanism of osteosarcoma (OS)-specific markers to mitigate bone destruction in the aggressive OS, prone to recurrence and metastasis. Methods: Gene expression patterns from the Gene Expression Omnibus (GEO) database (GSE126209) were analyzed using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) modeling, and survival analysis to identify charged multivesicular body protein 4C (CHMP4C). Subsequently, its role in regulating the immune system and immune cell infiltration was explored. CHMP4C expression and signaling molecules in OS were assessed in osteosarcoma cell lines (MG63, U2OS, HOS) and hFOB1.19 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The impact of CHMP4C upregulation and interference on OS-related signaling molecules in MG63 cells was studied. Functional validation of CHMP4C in MG63 OS cells was confirmed through cell counting Kit-8 (CCK-8), transwell, and colony formation assays. In vivo experiments were conducted using Specific Pathogen Free (SPF)-grade male BALB/C nude mice for OS xenograft studies. Results: Based on the gene expression profiles analysis of six osteosarcoma samples and six normal tissue samples, we identified 1,511 upregulated DEGs and 5,678 downregulated DEGs in normal tissue samples. A significant positive correlation between the "yellow-green" module and OS was found through WGCNA analysis. Expression levels of CHMP4C, phosphorylated Glycogen Synthase Kinase 3β (p-GSK3β), and β-catenin were notably higher in U2OS, HOS, and MG63 OS cells than in hFOB1.19 human osteoblasts. Overexpressing CHMP4C in MG63 OS cells upregulated CHMP4C, p-GSK3β, and β-catenin while downregulating GSK3β, leading to increased proliferation and migration of MG63 cells. Conversely, interrupting CHMP4C had the opposite effect. High expression of CHMP4C significantly accelerated the growth of OS in nude mice, resulting in substantial upregulation of CHMP4C, p-GSK3β, and β-catenin expression and suppression of Glycogen Synthase Kinase 3β (GSK3β) expression in OS tissues. Conclusion: CHMP4C may serve as a specific immunomodulatory gene for OS. Its activation of the Wnt/β-catenin signaling pathway, mainly by increasing the phosphorylation echelon of GSK3β, promotes the invasion and spread of OS.

MSRB2 Ameliorates H2O2-induced Chondrocyte Oxidative Stress and Suppresses Apoptosis in Osteoarthritis

ABSTRACT Background Chondrocyte oxidative stress and apoptosis are critical factors contributing to the pathogenesis of osteoarthritis (OA). Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cells from oxidative stress and is involved in apoptosis. This study aimed to investigated the expression of MSRB2 in articular cartilage tissues and elucidated its effect on H2O2-stimulated chondrocytes. Methods Human chondrocytes were cultured in Dulbecco’s modified Eagle’s medium (DMEM)/F12. MSRB2 overexpression in chondrocytes was achieved by transfecting with an MSRB2 overexpression plasmid. Western blot, quantitative RT-PCR, Immunofluorescence staining, and TUNEL assay were employed in this study. Results MSRB2 expression was found to be reduced in OA patients. Furthermore, overexpression of MSRB2 in H2O2-induced chondrocytes mitigated apoptosis and enhanced cell viability. Elevated MSRB2 expression diminished chondrocyte ROS contents, decreased cytochrome C (Cyc) in the cytoplasm, and regulated mitochondrial membrane potential to maintain mitochondrial homeostasis. Interestingly, knockdown of charged multivesicular body protein 5 (CHMP5) led to a decreased inMSRB2 expression in chondrocytes. Additionally, protein levels of CHMP5 and MSRB2 were reduced in H2O2-stimulated chondrocytes, and silencing CHMP5 reduced MSRB2 expression. Knockdown of CHMP5 increased cleaved caspase-3 expression in H2O2-induced chondrocytes and elevated TUNEL-positive chondrocytes. Conclusion MSRB2 decreased in OA, and overexpression of MSRB2 alleviated oxidative stress and apoptosis of chondrocyte.

Adiabatic inspirals under electromagnetic radiation reaction on Kerr spacetime

A compact body in orbit about a black hole loses orbital energy and angular momentum through radiation-reaction processes, inspiralling toward the black hole until a final plunge. Here we consider a scenario with a charged compact body in which fluxes of electromagnetic radiation drive this inspiral. We calculate trajectories in the (p,e) plane for inspirals in the equatorial plane of a rotating black hole within the adiabatic (orbital-averaged-dissipative) approximation. We make comparisons with a nonrelativistic Keplerian approximation based on the Abraham-Lorentz force law, and with standard gravitational-wave driven scenarios. We find that EM-driven inspirals are less efficiently circularized (i.e. orbits remain more eccentric at the point of plunge) than their gravitational counterparts, and we quantify the effect of black hole spin. Published by the American Physical Society 2024

Modulating Golgi Stress Signaling Ameliorates Cell Morphological Phenotypes Induced by CHMP2B with Frontotemporal Dementia-Associated p.Asp148Tyr.

Some charged multivesicular body protein 2B (CHMP2B) mutations are associated with autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTDALS7). The main aim of this study is to clarify the relationship between the expression of mutated CHMP2B protein displaying FTD symptoms and defective neuronal differentiation. First, we illustrate that the expression of CHMP2B with the Asp148Tyr (D148Y) mutation, which preferentially displays FTD phenotypes, blunts neurite process elongation in rat primary cortical neurons. Similar results were observed in the N1E-115 cell line, a model that undergoes neurite elongation. Second, these effects were also accompanied by changes in neuronal differentiation marker protein expression. Third, wild-type CHMP2B protein was indeed localized in the endosomal sorting complexes required to transport (ESCRT)-like structures throughout the cytoplasm. In contrast, CHMP2B with the D148Y mutation exhibited aggregation-like structures and accumulated in the Golgi body. Fourth, among currently known Golgi stress regulators, the expression levels of Hsp47, which has protective effects on the Golgi body, were decreased in cells expressing CHMP2B with the D148Y mutation. Fifth, Arf4, another Golgi stress-signaling molecule, was increased in mutant-expressing cells. Finally, when transfecting Hsp47 or knocking down Arf4 with small interfering (si)RNA, cellular phenotypes in mutant-expressing cells were recovered. These results suggest that CHMP2B with the D148Y mutation, acting through Golgi stress signaling, is negatively involved in the regulation of neuronal cell morphological differentiation, providing evidence that a molecule controlling Golgi stress may be one of the potential FTD therapeutic targets at the molecular and cellular levels.

MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.

The role of autophagy in pulmonary microvascular endothelial cells (PMVECs) is controversial in LPS-induced acute lung injury (ALI). Mixed lineage kinase domain-like pseudokinase (MLKL) has recently been reported to maintain cell survival by facilitating autophagic flux in response to starvation rather than its well-recognized role in necroptosis. Using a mouse PMVEC and LPS-induced ALI model, we showed that in PMVECs, MLKL was phosphorylated (p-MLKL) and autophagic flux was accelerated at the early stage of LPS stimulation (1-3 h), manifested by increases in concentrations of lipidated MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β; LC3-II), decreases in concentrations of SQSTM1/p62 (sequestosome 1), and fusion of the autophagosome and lysosome by pHluorin-mKate2-human LC3 assay, which were all reversed by either MLKL inhibitor or siRNA MLKL. In mice, the inhibition of MLKL increased vascular permeability and aggravated mouse ALI upon 3-hour LPS stimulation. The p-MLKL induced by short-term LPS formed multimers to facilitate the closure of the phagophore by HaloTag-LC3 autophagosome completion assay. The charged multivesicular body protein 2A (CHMP2A) is essential in the process of phagophore closure into the nascent autophagosome. In agreement with the p-MLKL change, CHMP2A concentrations markedly increased during 1-3-hour LPS stimulation. CHMP2A knockdown blocked autophagic flux upon LPS stimulation, whereas CHMP2A overexpression boosted autophagic flux and attenuated mouse ALI even in the presence of MLKL inhibitor. We propose that the activated MLKL induced by short-term LPS facilitates autophagic flux by accelerating the closure of the phagophore via CHMP2A, thus protecting PMVECs and alleviating LPS-induced ALI.

Identification of a PANoptosis-related Gene Signature for Predicting the Prognosis, Tumor Microenvironment and Therapy Response in Breast Cancer.

Breast cancer (BC) is the most prevalent malignancy among women worldwide. Mounting evidence suggests that PANoptosis participates in cancer development and therapy. However, the role of PANoptosis in BC remains unclear. In this study, we identified ten PANoptosis-related genes using Cox regression analysis, random forest (RF) algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. A PANoptosis-related score (PRS) was calculated based on the coefficient of LASSO. Notably, we divided the patients into high- and low-risk groups according to the PRS and revealed a negative correlation between PRS and overall survival. Next, a nomogram model was constructed and validated to improve the clinical application of PRS. Functional enrichment analyses and the Bayesian network demonstrated that differentially expressed genes between high- and low-risk groups were mainly enriched in immune-related pathways. Besides, we found significant differences in tumor mutation burden and tumor immune microenvironment between patients in these two groups using bulk-RNA and single-cell RNA sequencing data. Furthermore, charged multivesicular body protein 2B (CHMP2B) was identified as the hub gene by combining LASSO, weighted gene co-expression network analysis, RF and eXtreme Gradient Boosting. Importantly, using immunohistochemistry analysis based on our tissue microarray, we found that CHMP2B was highly expressed in tumor tissue, and CD4 and CD8 were more likely to be positive in the CHMP2B-negative group. Survival analyses revealed that CHMP2B adversely impacted the survival of BC patients. In conclusion, we not only constructed a highly accurate predictive model based on PRS, but also revealed the importance of PANoptosis-related gene signature in the modulation of the tumor microenvironment and drug sensitivity in BC.

CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase‑1‑dependent pyroptosis.

Charged multivesicular body protein3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT)III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocellular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohistochemistry and western blot analysis. Subsequently, HepG2 and Huh‑7cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit‑8 assays. Wound healing and Transwell assays were used to examine the migratory and invasive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blotting was used to examine the expression of caspase‑1 signaling pathway related proteins, a classic pathway of pyroptosis. In addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 invivo. The results demonstrated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overexpression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh‑7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase‑1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase‑1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase‑1‑mediated pyroptosis pathway.

Studying the influence of a gyrostatic moment on the motion of a charged rigid body containing a viscous incompressible liquid

The rotational motion of a charged rigid body (RB) is examined. The RB has a spherical cavity that contains an incompressible viscous liquid. The influence of a gyrostatic moment (GM), constant torques at the body-connected axes, and the action of the torque of a resistant force, due to the shape of the liquid, are considered. Assuming the liquid has a sufficiently high velocity, the Reynolds number does indeed have a small value. The regulating system of motion is derived in an appropriate formulation through Euler's equations of motion. The averaging method is used to approach a suitable form of the motion's governing system. In addition to using Taylor’s method to reach a solution for the averaged equations of motion of the RB, some initial conditions are considered to approach the required results. The asymptotic approach of the averaged system besides the numerical analysis enables us to obtain the appropriate results of the problem. To draw attention to the beneficial effects of the different values of the body’s parameter on the motion's behavior, these results are graphed through a computer program along with the associated phase plane curves. These diagrams illustrate the influence of several values respected to the GM, charge, body-constant torques, and resistive force torque. The stability of the RB's motion has also been discussed through the represented phase plane diagrams. These results are viewed as a generalization of prior ones, which have been reported for the scenario of an uncharged body or the absence case of the GM. The significance of the obtained results is due to its numerous real-world applications in life, such as for spaceships and wagons carrying liquid fuel.