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Background: Imatinib has become an exceptionally effective targeted drug for treating gastrointestinal stromal tumors (GISTs). Despite its efficacy, the resistance to imatinib is common in GIST patients, posing a significant challenge to the effective treatment. Methods: The expression profiling of TRIM21, USP15, and ACSL4 in GIST patients was evaluated using Western blot and immunohistochemistry. To silence gene expression, shRNA was utilized. Biological function of TRIM21, USP15, and ACSL4 was examined through various methods, including resistance index calculation, colony formation, shRNA interference, and xenograft mouse model. The molecular mechanism of TRIM21 and USP15 in GIST was determined by conducting Western blot, co-immunoprecipitation, and quantitative real-time PCR (qPCR) analyses. Results: Here we demonstrated that downregulation of ACSL4 is associated with imatinib (IM) resistance in GIST. Moreover, clinical data showed that higher levels of ACSL4 expression are positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that the reduced expression of ACSL4 in GIST is attributed to excessive protein degradation mediated by the E3 ligase TRIM21 and the deubiquitinase USP15. Conclusion: These findings demonstrate that the TRIM21 and USP15 control ACSL4 stability to maintain the IM sensitive/resistant status of GIST. [ABSTRACT FROM AUTHOR]

Hypoxia-mediated chemoresistance plays a crucial role in the development of ovarian cancer (OC). However, the roles of hypoxia-related genes (HRGs) in chemoresistance and prognosis prediction and theirs underlying mechanisms remain to be further elucidated. We intended to identify and validate classifiers of hub HRGs for chemoresistance, diagnosis, prognosis as well as immune microenvironment of OC, and to explore the function of the most crucial HRG in the development of the malignant phenotypes. The RNA expression and clinical data of HRGs were systematically evaluated in OC training group. Univariate and multivariate Cox regression analysis were applied to construct hub HRGs classifiers for prognosis and diagnosis assessment. The relationship between classifiers and chemotherapy response and underlying pathways were detected by GSEA, CellMiner and CIBERSORT algorithm, respectively. OC cells were cultured under hypoxia or transfected with HIF-1α or HIF-2α plasmids, and the transcription levels of TGFBI were assessed by quantitative PCR. TGFBI was knocked down by siRNAs in OC cells, CCK8 and in vitro migration and invasion assays were performed to examine the changes in cell proliferation, motility and metastasis. The difference in TGFBI expression was examined between cisplatin-sensitive and -resistant cells, and the effects of TGFBI interference on cell apoptosis, DNA repair and key signaling molecules of cisplatin-resistant OC cells were explored. A total of 179 candidate HRGs were extracted and enrolled into univariate and multivariate Cox regression analysis. Six hub genes (TGFBI, CDKN1B, AKAP12, GPC1, TGM2 and ANGPTL4) were selected to create a HRGs prognosis classifier and four genes (TGFBI, AKAP12, GPC1 and TGM2) were selected to construct diagnosis classifiers. The HRGs prognosis classifier could precisely distinguish OC patients into high-risk and low-risk groups and estimate their clinical outcomes. Furthermore, the high-risk group had higher percentage of Macrophages M2 and exhibited higher expression of immunecheckpoints such as PD-L2. Additionally, the diagnosis classifiers could accurately distinguish OC from normal samples. TGFBI was further verified as a specific key target and demonstrated that its high expression was closely correlated with poor prognosis and chemoresistance of OC. Hypoxia upregulated the expression level of TGFBI. The hypoxia-induced factor HIF-2α but not HIF-1α could directly bind to the promoter region of TGFBI, and facilitate its transcription level. TGFBI was upregulated in cisplatin-sensitive and resistant ovarian cancer cells in a cisplatin time-dependent manner. TGFBI interference downregulated DNA repair-related markers (p-p95/NBS1, RAD51, p-DNA-PKcs, DNA Ligase IV and Artemis), apoptosis-related marker (BCL2) and PI3K/Akt pathway-related markers (PI3K-p110 and p-Akt) in cisplatin-resistant OC cells. In summary, the HRGs prognosis risk classifier could be served as a predictor for OC prognosis and efficacy evaluation. TGFBI, upregulated by HIF-2α as an HRG, promoted OC chemoresistance through activating PI3K/Akt pathway to reduce apoptosis and enhance DNA damage repair pathway. [ABSTRACT FROM AUTHOR]

The security context, generally stored in the universal subscriber identity module card or the baseband chip, is the critical information applied by the subscriber to access the 5G network during the fast authentication procedure. Once exposed or illegally used, the security context can be exploited to derive various keys for authentication and encryption. Despite its importance, challenges and questions still remain in the previous relevant research. To fill this gap, by adopting the security protocol verification tool ProVerif, we provide a comprehensive formal model of the fast authentication procedure based on the security context to analyze whether security goals can be met. Unfortunately, we uncover two vulnerabilities, including one never reported before. Our analysis shows that these vulnerabilities stem from fundamental design flaws in the cellular network protocol and thus apply to the 4G network. These vulnerabilities could be exploited to launch several attacks, including impersonation and eavesdropping. We have validated these attacks using 5 mobile phones from 5 different baseband manufacturers through experimentation in three mobile carriers. We find an insecure implementation of one of these phones, which exposed it to replay attacks. And we further discuss the security threats posed by the impersonation attack, such as location spoofing and one-tap authentication bypass, which is verified on 10 popular apps. We finally propose several countermeasures to eliminate these security issues. Actually, we have reported the novel vulnerability to the GSM Association and received a confirmation in the form of a coordinated vulnerability disclosure (CVD) number CVD-2022-0057. [ABSTRACT FROM AUTHOR]

Background: G protein-coupled receptors (GPCRs) have been shown to have an important role in tumor development and metastasis, and abnormal expression of GPCRs is significantly associated with poor prognosis of tumor patients. In this study, we analyzed the GPCRs-related gene (GPRGs) and tumor microenvironment (TME) in skin cutaneous melanoma (SKCM) to construct a prognostic model to help SKCM patients obtain accurate clinical treatment strategies. Methods: SKCM expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression analysis, LASSO algorithm, and univariate and multivariate cox regression analysis were used to screen prognosis-related genes (GPR19, GPR146, S1PR2, PTH1R, ADGRE5, CXCR3, GPR143, and OR2I1P) and multiple prognosis-good immune cells; the data set was analyzed according to above results and build up a GPR-TME classifier. The model was further subjected to immune infiltration, functional enrichment, tumor mutational load, immunotherapy prediction, and scRNA-seq data analysis. Finally, cellular experiments were conducted to validate the functionality of the key gene GPR19 in the model. Results: The findings indicate that high expression of GPRGs is associated with a poor prognosis in patients with SKCM, highlighting the significant role of GPRGs and the tumor microenvironment (TME) in SKCM development. Notably, the group characterized by low GPR expression and a high TME exhibited the most favorable prognosis and immunotherapeutic efficacy. Furthermore, cellular assays demonstrated that knockdown of GPR19 significantly reduced the proliferation, migration, and invasive capabilities of melanoma cells in A375 and A2058 cell lines. Conclusion: This study provides novel insights for the prognosis evaluation and treatment of melanoma, along with the identification of a new biomarker, GPR19. [ABSTRACT FROM AUTHOR]

Background: The incidence of skin cutaneous melanoma (SKCM), one of the most aggressive and lethal skin tumors, is increasing worldwide. However, for advanced SKCM, we still lack an accurate and valid way to predict its prognosis, as well as novel theories to guide the planning of treatment options for SKCM patients. Lactylation (LAC), a novel post-translational modification of histones, has been shown to promote tumor growth and inhibit the antitumor response of the tumor microenvironment (TME) in a variety of ways. We hope that this study will provide new ideas for treatment options for SKCM patients, as well as research on the molecular mechanisms of SKCM pathogenesis and development. Methods: At the level of the RNA sequencing set (TCGA, GTEx), we used differential expression analysis, LASSO regression analysis, and multifactor Cox regression analysis to screen for prognosis-related genes and calculate the corresponding LAC scores. The content of TME cells in the tumor tissue was calculated using the CIBERSORT algorithm, and the TME score was calculated based on its results. Finally, the LAC–TME classifier was established and further analyzed based on the two scores, including the construction of a prognostic model, analysis of clinicopathological characteristics, and correlation analysis of tumor mutation burden (TMB) and immunotherapy. Based on single-cell RNA sequencing data, this study analyzed the cellular composition in SKCM tissues and explored the role of LAC scores in intercellular communication. To validate the functionality of the pivotal gene CLPB in the model, cellular experiments were ultimately executed. Results: We screened a total of six prognosis-related genes (NDUFA10, NDUFA13, CLPB, RRM2B, HPDL, NARS2) and 7 TME cells with good prognosis. According to Kaplan–Meier survival analysis, we found that the LAClow/TMEhigh group had the highest overall survival (OS) and the LAChigh/TMElow group had the lowest OS (p value < 0.05). In further analysis of immune infiltration, tumor microenvironment (TME), functional enrichment, tumor mutational load and immunotherapy, we found that immunotherapy was more appropriate in the LAClow/TMEhigh group. Moreover, the cellular assays exhibited substantial reductions in proliferation, migration, and invasive potentials of melanoma cells in both A375 and A2058 cell lines upon CLPB knockdown. Conclusions: The prognostic model using the combined LAC score and TME score was able to predict the prognosis of SKCM patients more consistently, and the LAC–TME classifier was able to significantly differentiate the prognosis of SKCM patients across multiple clinicopathological features. The LAC–TME classifier has an important role in the development of immunotherapy regimens for SKCM patients. [ABSTRACT FROM AUTHOR]

Background: The involvement of ferroptosis in the pathogenesis and progression of various cancers has been well established. However, limited studies have investigated the role of ferroptosis-mediated tumor microenvironment (TME) in skin cutaneous melanoma (SKCM). Methods: By leveraging single-cell RNA sequencing data, the nonnegative matrix factorization (NMF) approach was employed to comprehensively characterize and identify distinct gene signatures within ferroptosis-associated TME cell clusters. Prognostic and treatment response analyses were conducted using both bulk datasets and external cancer cohort to evaluate the clinical implications of TME clusters. Results: This NMF-based analysis successfully delineated fibroblasts, macrophages, T cells, and B cells into multiple clusters, enabling the identification of unique gene expression patterns and the annotation of distinct TME clusters. Furthermore, pseudotime trajectories, enrichment analysis, cellular communication analysis, and gene regulatory network analysis collectively demonstrated significant intercellular communication between key TME cell clusters, thereby influencing tumor cell development through diverse mechanisms. Importantly, our bulk RNA-seq analysis revealed the prognostic significance of ferroptosis-mediated TME cell clusters in SKCM patients. Moreover, our analysis of immune checkpoint blockade highlighted the crucial role of TME cell clusters in tumor immunotherapy, facilitating the discovery of potential immunotherapeutic targets. Conclusions: In conclusion, this pioneering study employing NMF-based analysis unravels the intricate cellular communication mediated by ferroptosis within the TME and its profound implications for the pathogenesis and progression of SKCM. We provide compelling evidence for the prognostic value of ferroptosis-regulated TME cell clusters in SKCM, as well as their potential as targets for immunotherapy. [ABSTRACT FROM AUTHOR]

Explore the hydrochemical characteristics of surface water (SW) and groundwater (GW) under coal mining activities and controlling factors is essential to ensure water security. This research concentrates on the Changhe River Basin (CRB). Water samples were collected from 27 sites within the CRB in May, July and December 2022. A qualitative analysis of hydrochemical characteristics and major ion sources was conducted based on Piper plots, Gibbs plots, Pearson correlation analysis and ion ratio methods. The PCA ~ RSR model was used to assess the current status of SW and GW quality in the CRB. We found that the hydrochemical type of SW and GW is HCO3–Ca, with HCO3− accounting for 62.2% ~ 87.9% of the total anions and Ca2+ accounting for 27.4% ~ 31.3% of the total cations. Rock weathering is the main factor affecting the hydrochemical of CRB. SW is affected by the weathering and dissolution of both silicate and carbonate rocks, while GW is mainly affected by the weathering and dissolution of silicate. The cation exchange also has influence on GW. The cations in the water are mainly derived from rock weathering dissolution and exchange reactions, while SO42− in anions is mainly imported from outside. The results of the water quality assessment showed that water quality in the midstream of the study area is poor and coal mining has seriously affected water safety issues. The study reveals the impact of coal mining on hydrochemical. It provides a scientific basis for the protection and management of water resources under coal mining activities in arid and semi-arid regions. [ABSTRACT FROM AUTHOR]

Healthy cartilage is a water-filled super lubricious tissue. Collagen type II provides it structural stability, and proteoglycans absorb water to keep the cartilage in a swollen condition, providing it the ability to creep and provide weeping lubrication. Osteoarthritis (OA) is a degenerative and debilitating disorder of diarthrodial joints, where articular cartilage damage originates from enzymatic degradation and mechanical damage (wear). The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in vitro. Lateral (Lat) and medial (Med) condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical damage. Bovine cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans, respectively. The loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope (AFM), respectively. A significant effect on creep due to enzymatic treatment was not observed. But the enzymatic treatment was found to significantly decrease the coefficient of friction (COF) at 4 N, while higher COF was shown from chondroitinase ABC degraded cartilage at 40 N. Collagenase III treatment leads to the release of intact proteoglycans at the sliding interface, while chondroitinase ABC treatment leads to the loss of chondroitin sulfate (CS) from the proteoglycans. Chondroitinase ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans, collagen network, and friction behavior. [ABSTRACT FROM AUTHOR]

Exploring the impact of land use and slope on basin water quality can effectively contribute to the protection of the latter at the landscape level. This research concentrates on the Weihe River Basin (WRB). Water samples were collected from 40 sites within the WRB in April and October 2021. A quantitative analysis of the relationship between integrated landscape pattern (land use type, landscape configuration, slope) and basin water quality at the sub-basin, riparian zone, and river scales was conducted based on multiple linear regression analysis (MLR) and redundancy analysis (RDA). The correlation between water quality variables and land use was higher in the dry season than in the wet season. The riparian scale was the best spatial scale model to explain the relationship between land use and water quality. Agricultural and urban lands had a strong correlation with water quality, which was most affected by land use area and morphological indicators. In addition, the greater the area and aggregation of forest land and grassland, the better the water quality, while urban land presented larger areas with poorer water quality. The influence of steeper slopes on water quality was more remarkable than that of plains at the sub-basin scale, while the impact of flatter areas was greater at the riparian zone scale. The results indicated the importance of multiple time–space scales to reveal the complex relationship between land use and water quality. We suggest that watershed water quality management should focus on multi-scale landscape planning measures. [ABSTRACT FROM AUTHOR]

Tumor cell-derived vesicles are released by tumor cells, have a phospholipid bilayer, and are widely distributed in various biological fluids. In recent years, it has been found that tumor cell-derived vesicles contain proteins, metabolites and nucleic acids and can be delivered to recipient cells to perform their physiological functions, such as mediating specific intercellular communication, activating or inhibiting signaling pathways, participating in regulating the modulation of tumor microenvironment and influencing tumor development, which can be used for early detection and diagnosis of cancer. In addition, tumor cell-derived vesicles exhibit multiple properties in tumor therapeutic applications and may serve as a new class of delivery systems. In this review, we elaborate on the application of tumor cell-derived vesicles in oncology therapy. [ABSTRACT FROM AUTHOR]

The self-focusing properties of the Laguerre–Gaussian beams in nonlinear plasma, characterized by significant collisional or ponderomotive nonlinearity have been explored. The second-order differential equation of the beam width is established from Maxwell's equations with Wentzel–Kramers–Brillouin and paraxial like approximation. The effect of the vortex charge number, intensity parameter and plasma temperature on the self-focusing properties of the Laguerre–Gaussian beam has been investigated. [ABSTRACT FROM AUTHOR]

This paper proposes a fault diagnosis method for electrical machine drive system by using backpropagation neural network (BPNN) optimized by chaotic adaptive gravity search algorithm (GSA) and particle swarm optimization (PSO) algorithm. In this method, an adaptive gravitational constant factor based on iteration times and chaotic mapping is introduced to balance the global search ability and local development ability of GSA. Then, it is combined with PSO algorithm to solve the problem of prematurity and local optimum of PSO algorithm. Finally, combined with BPNN, a fault diagnosis model based on chaos adaptive GSA-PSO-BPNN is established. The experimental results show that the introduction of the attenuation factor of adaptive gravitational constant and the chaotic mapping can improve the classification performance of GSA-PSO-BPNN, and the feasibility and effectiveness of the chaotic adaptive GSA-PSO Algorithm are also proved. [ABSTRACT FROM AUTHOR]

Rotation axes have been proven to be the greatest factor leading to machine tool errors, which seriously affect the machining accuracy. Therefore, it is imperative to identify the geometric errors of the rotation axes. This research focuses on how to identify the critical geometric errors of the rotation axes, so that the coupling effect of geometric errors which seriously affects the identification of geometric errors of the rotation axes can be examined. To achieve this goal, this paper proposes a global quantitative sensitivity analysis method based on homogeneous transformation matrix (HTM) theory and Sobol sensitivity analysis method. The size and randomness of geometric errors are taken into consideration and the specific indexing angles of the rotation axes are introduced to identify the critical geometric errors of the five-axis machine tool. Based on this analysis method, each geometric error components and the coupling effect between different error sources are evaluated under different indexing angles. The variation of the coupling effect of each error components within the traverse of the rotation axes is explored. The geometric error measurement experiment is established and the results are compared with the simulation results. The simulation results and experimental results reveal that the critical geometric errors that affect the machining accuracy and the variation of the geometric errors coupling effect, which provides useful guidance for the manufacturers and users of five-axis machine tools. [ABSTRACT FROM AUTHOR]

As a kind of non-diffracting beam, optical needle is gaining increased attention for its interesting properties and various potential applications. In this paper, we theoretically investigate the optical trapping force and torque on a Rayleigh spheroidal particle by an optical needle. A strategy to realize a non-diffracting optical needle by focusing a radially polarized vortex (RPV) beam with a high numerical aperture (NA) lens system is introduced and a diffractive optical element (DOE) is adopted to control the field distribution of the optical needle. Based on the field expressions of the optical needle derived through the Richards and Wolf theory, the factors affecting the properties of the optical needle are examined. Within the framework of dipole approximation, the optical trapping force and torque of an optical needle on a prolate spheroid with any spatial orientation are calculated. Numerical results show that the trapping force and torque are significantly affected by the field distribution of the optical needle, as well as the ellipticity and orientation of the spheroid. The present study may provide useful insights into the dynamic behavior during an actual optical trapping. [ABSTRACT FROM AUTHOR]

Monotonicity is an appealing principle of relational power measures in social networks. It states that as the influence of an individual changes, the relational power measure should change in the same direction. We axiomatically characterize the β - and score-measures on directed networks using three axioms: two different monotonicity axioms, the same symmetry axiom and two different efficiency axioms, respectively. For every individual, the β -measure refers to a weighted sum over all dominated individuals by itself, in which for each dominated individual the weight is given by the reciprocal of the number of its dominators, while the score-measure refers simply to the number of dominated individuals by itself. We also extend the result for the score-measure to undirected networks. [ABSTRACT FROM AUTHOR]

This paper develops a coevolutionary model of social coordination and matching in which agents are embedded in an arbitrary fixed network and are matched in pairs to play a coordination game. In each period, based on payoff comparison with their neighbors, agents decide whether to imitate their neighbors' actions and whether to end their present partnerships. Inertia exists in action revision and partnership updating. Each agent can exit a partnership unilaterally. All separated agents are randomly matched in pairs at the beginning of the next period. Occasionally, agents make mistakes in action revision and partnership updating. When the size of the society is large, in the long run, all agents will play the Pareto-efficient action for a particular subset of networks. [ABSTRACT FROM AUTHOR]

Sensitization and activation of the trigeminal ganglia have been implicated in the pathology of migraine. Satellite glial cells (SGCs), a specialized type of glial cells that ensheathe trigeminal neurons, may be critical for peripheral nociceptive sensitization. Tetrandrine (TET), an alkaloid extracted from a traditional Chinese herb, exerts an inhibitory effect on glial activation in vitro and has been used in various neurologic diseases. The current study investigated the effect of TET on nitroglycerin (NTG)-induced trigeminal sensitization and examined potential signaling pathways related to SGC activation in the model of migraine. We measured trigeminal nociceptive thresholds using electronic von Frey rigid tips before and after NTG injection in control rats and rats pretreated with TET, while expression and subcellular location of the inflammatory mediators S100B and activated phosphorylation extracellular signal-regulated kinase (p-ERK) were measured using real-time quantitative polymerase chain reaction, Western blotting, and double immunofluorescence staining. Pretreatment with TET caused a dose-dependent reversal of the trigeminal nociceptive hypersensitivity induced by NTG. In addition, TET pretreatment blocked the activation of S100B and p-ERK in trigeminal ganglion SGCs of NTG-treated rats. Reduced p-ERK activity can suppress the inflammation that leads to hyperexcitability of trigeminal ganglion neurons. Administration of TET may therefore be a safe and effective therapeutic treatment for the hyperalgesic symptoms of migraine. [ABSTRACT FROM AUTHOR]

This paper considers a Schelling model in an arbitrary fixed network where there are no vacant houses. Agents have preferences either for segregation or for mixed neighborhoods. Utility is non-transferable. Two agents exchange houses when the trade is mutually beneficial. We find that an allocation is stable when for two agents of opposite-color each black (white) agent has a higher proportion of neighbors who are black (white). This result holds irrespective of agents' preferences. When all members of both groups prefer mixed neighborhoods, an allocation is also stable provided that if an agent belongs to the minority (majority), then any neighbor of opposite-color is in a smaller minority (larger majority). [ABSTRACT FROM AUTHOR]

This study proposes the ontological reconstruction of the current clinical terminology of traditional Chinese medicine (TCM). It also provides an overview of preliminary work related to the said reconstruction, including the ontology-based analysis of TCM clinical terminology. We conclude that the ontological reconstruction of TCM clinical terminology provides a proper translation from the idealized organizational model to real-world implementation and to a formalized, shared, and knowledge-based framework. [ABSTRACT FROM AUTHOR]

We establish the standard procedures in solving a class of dynamic stochastic general equilibrium models with a second-order approximation to the policy function. The innovation is that the means of exogenous shocks vary with the variances. The numerical results show that second-order perturbation methods generate large approximation errors regarding to the responses of policy functions to shocks. [ABSTRACT FROM AUTHOR]

In classic molecular dynamics (MD) simulations, the conventional Verlet table, cell linked list and many other techniques have been adopted to increase the computational efficiency. However, these methods are only applicable in cubic systems. In this work, the above techniques along with the metric-tensor method are extended to handle NP ensembles, so that MD simulations can be carried out under the most general loading conditions. In order to do so, a particular spatial Cartesian reference frame is proposed to determine the scaling matrix. Also, a combination method, taking the advantages of the improved Verlet table and cell linked list, is established to identify the neighbor atoms very quickly in a parallelepiped box. An example using Lennard-Jones potential is presented to verify the validity of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Analytical formulas of the propagation parameters (including the angular width and propagation factor) of the Lommel–Gaussian beams in atmospheric turbulence are derived on the basis of extended Huygens–Fresnel integral and second-order moments of Wigner distribution function. Evolution properties of the propagation parameters of Lommel–Gaussian beams propagating in atmospheric turbulence are investigated numerically. The results show that the Lommel–Gaussian beams are less affected with smaller structure constant, as well as bigger orbital angular momentum quantum number, wavelength, and inner scale. Furthermore, the beam propagation is independent of the modulus of the asymmetry parameter. The results may be useful for the practical application of the Lommel–Gaussian beam in free space optical communications. [ABSTRACT FROM AUTHOR]