Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways.

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.

Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment.

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.

Bioinformatic Profiling of Prognosis-Related Genes in Malignant Glioma Microenvironment.

BACKGROUND Gliomas are the most common primary tumors of the brain and spinal cord. The tumor microenvironment (TME) is the cellular environment in which tumors exist. This study aimed to identify the role of the TME and the effects of genes involved in the TME of malignant glioma. MATERIAL AND METHODS The ESTIMATE algorithms in the R package were used to calculate the immune and stromal scores of samples in the TCGA and GSE4290 datasets. The associations of stromal and immune scores with clinicopathological characteristics and overall survival of malignant glioma patients were assessed by analysis of variance and Kaplan-Meier analysis. Differentially expressed genes (DEGs) were obtained through the median immune and stromal score using the R package "limma". Functional enrichment analysis and the PPI network MCODE were used to analyze DEGs. RESULTS Increased immune and stromal scores were closely related with advanced glioma grade and poor prognosis (all P<0.01). In total, 558 DEGs were found and most were related to tumor prognosis. Functional enrichment analysis showed that DEGs were associated with cell-matrix regulation and immune response. Four hub modules related to tumor angiogenesis, collagen formation, and immune response were found and analyzed. Previously overlooked microenvironment-related genes such as LAMB1, FN1, ACTN1, TRIM, SERPINH1, CYBA, LAIR1, and LILRB2 showed prognostic values in malignant glioma patients. CONCLUSIONS The glioma stromal/immune scores are closely related to glioma grade, histology, and survival time. Some glioma microenvironment-related genes including LAMB1, FN1, ACTN1, TRIM6, SERPINH1, CYBA, LAIR1, and LILRB2 show prognostic values in malignant gliomas and serve as potential biomarkers.

Orthogonal Subspace Representation for Generative Adversarial Networks.

Disentanglement learning aims to separate explanatory factors of variation so that different attributes of the data can be well characterized and isolated, which promotes efficient inference for downstream tasks. Mainstream disentanglement approaches based on generative adversarial networks (GANs) learn interpretable data representation. However, most typical GAN-based works lack the discussion of the latent subspace, causing insufficient consideration of the variation of independent factors. Although some recent research analyzes the latent space on pretrained GANs for image editing, they do not emphasize learning representation directly from the subspace perspective. Appropriate subspace properties could facilitate corresponding feature representation learning to satisfy the independent variation requirements of the obtained explanatory factors, which is crucial for better disentanglement. In this work, we propose a unified framework for ensuring disentanglement, which fully investigates latent subspace learning (SL) in GAN. The novel GAN-based architecture explores orthogonal subspace representation (OSR) on vanilla GAN, named OSRGAN. To guide a subspace with strong correlation, less redundancy, and robust distinguishability, our OSR includes three stages, self-latent-aware, orthogonal subspace-aware, and structure representation-aware, respectively. First, the self-latent-aware stage promotes the latent subspace strongly correlated with the data space to discover interpretable factors, but with poor independence of variation. Second, the following orthogonal subspace-aware stage adaptively learns some 1-D linear subspace spanned by a set of orthogonal bases in the latent space. There is less redundancy between them, expressing the corresponding independence. Third, the structure representation-aware stage aligns the projection on the orthogonal subspace and the latent variables. Accordingly, feature representation in each linear subspace can be distinguishable, enhancing the independent expression of interpretable factors. In addition, we design an alternating optimization step, achieving a tradeoff training of OSRGAN on different properties. Despite it strictly constrains orthogonality, the loss weight coefficient of distinguishability induced by orthogonality could be adjusted and balanced with correlation constraint. To elucidate, this tradeoff training prevents our OSRGAN from overemphasizing any property and damaging the expressiveness of the feature representation. It takes into account both interpretable factors and their independent variation characteristics. Meanwhile, alternating optimization could keep the cost and efficiency of forward inference unchanged and will not burden the computational complexity. In theory, we clarify the significance of OSR, which brings better independence of factors, along with interpretability as correlation could converge to a high range faster. Moreover, through the convergence behavior analysis, including the objective functions under different constraints and the evaluation curve with iterations, our model demonstrates enhanced stability and definitely converges toward a higher peak for disentanglement. To depict the performance in downstream tasks, we compared the state-of-the-art GAN-based and even VAE-based approaches on different datasets. Our OSRGAN achieves higher disentanglement scores on FactorVAE, SAP, MIG, and VP metrics. All the experimental results illustrate that our novel GAN-based framework has considerable advantages on disentanglement.

Aberrant resting-state voxel-mirrored homotopic connectivity in major depressive disorder with and without anxiety.

OBJECTIVE: Prior researchers have identified distinct differences in functional connectivity neuroimaging characteristics among MDD patients. However, the auxiliary diagnosis and subtype differentiation roles of VMHC values in MDD patients have yet to be fully understood. We aim to explore the separating ability of VMHC values in patients with anxious MDD or with non-anxious MDD and HCs. METHODS: We recruited 90 patients with anxious MDD, 69 patients with non-anxious MDD and 84 HCs. We collected a set of clinical variables included HAMD-17 scores, HAMA scores and rs-fMRI data. The data were analyzed combining difference analysis, SVM, correlation analysis and ROC analysis. RESULTS: Relative to HCs, non-anxious MDD patients displayed significant lower VMHC values in the insula and PCG, and anxious MDD patients displayed a significant decrease in VMHC values in the cerebellum_crus2, STG, postCG, MFG and IFG. Compared with non-anxious MDD patients, the anxious MDD showed significant enhanced VMHC values in the PCG. The VMHC values in the insula and cerebellum_crus2 regions showed a better ability to discriminate HCs from patients with non-anxious MDD or with anxious MDD. The VMHC values in PCG showed a better ability to discriminate patients with anxious MDD and non-anxious MDD patients. CONCLUSION: The VMHC values in the insula and cerebellum_crus2 regions could be served as imaging markers to differentiate HCs from patients with non-anxious MDD or with anxious MDD respectively. And the VMHC values in the PCG could be used to discriminate patients with anxious MDD from the non-anxious MDD patients.

New grading scale based on early factors for predicting delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: a multicenter retrospective study.

Delayed cerebral ischemia (DCI) could lead to poor clinical outcome(s). The aim of the present study was to establish and validate a predictive model for DCI after aneurysmal subarachnoid hemorrhage (aSAH) based on clinical data. Data from a series of 217 consecutive patients with aSAH were reviewed and analyzed. Related risk factors within 72 h after aSAH were analyzed depending on whether DCI recurred. Least absolute shrinkage and selection operator (LASSO) analysis was performed to reduce data dimensions and screen for optimal predictors. Multivariable logistic regression was used to establish a predictive model and construct a nomogram. Receiver operating characteristic (ROC) and calibration curves were generated to assess the discriminative ability and goodness of fit of the model. Decision curve analysis was applied to evaluated the clinical applicability of the predictive model. LASSO regression identified 4 independent predictors, including Subarachnoid Hemorrhage Early Brain Edema Score (i.e., "SEBES"), World Federation of Neurosurgical Societies scale score (i.e., "WFNS"), modified Fisher Scale score, and intraventricular hemorrhage (IVH), which were incorporated into logistic regression to develop a nomogram. After verification, the area under the ROC curve for the model was 0.860. The calibration curve indicated that the predictive probability of the new model was in good agreement with the actual probability, and decision curve analysis demonstrated the clinical applicability of the model within a specified range. The prediction model could precisely calculate the probability of DCI after aSAH, and may contribute to better clinical decision-making and personalized treatment to achieve better outcomes.

ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury.

Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.

Ferritin Light Chain Alleviates Cerebral Ischemic-Reperfusion Injury-Induced Neuroinflammation via the HIF1α Mediated NF-κB Signaling Pathways.

Ferritin light chain (FtL) is a complex formed by apoferritin and iron core and is one of the main storage forms of iron. Currently, the precise role of FtL in cerebral ischemia/reperfusion injury (CIRI) remains undetermined. This investigation aimed to elucidate the roles and underlying mechanisms of FtL in CIRI. To induce CIRI, an oxygen-glucose deprivation (OGD) model in microglia and middle cerebral artery occlusion (MCAO) model were established using C57BL/6 J mice. The in vivo and in vitro FtL expression patterns were assessed. Furthermore, the potential regulatory mechanism of FtL at the upstream level was also explored. In addition, the in vivo and in vitro role of FtL in post-ischemic inflammation was also clarified. The results indicated that FtL was up-regulated in OGD-induced microglia and CIRI mice. Moreover, OGD activated HIF1α, which interacted with the FtL promoter region as an activator, thereby increasing FtL expression. Furthermore, FtL attenuated the release of pro-inflammatory cytokines (TNFα, IL6) and decreased levels of COX2 and iNOS in microglia; however, FtL knockdown had the opposite effects. Up-regulated FtL was observed to inhibit OGD-induced NF-κB activation in microglia, decreased IκBα degradation, and reduced NF-κB/p65 nuclear translocation. In summary, this study revealed an underlying mechanism of FtL upregulation via HIF1α and highlighted its protective role against post-ischemic neuroinflammation, indicating the potential of FtL as a target for CIRI treatment.

TUG1 exacerbates cerebral ischemia-reperfusion injury through miR-340-5p-mediated PTEN.

Long non-coding RNAs (LncRNAs) play a substantial role in the process of cerebral ischemia-reperfusion injury (CIRI). The present work aimed to determine the probable mechanism by which LncRNA TUG1 exacerbates CIRI via the miR-340-5p/phosphatase and tensin homolog (PTEN) pathway. After developing a middle cerebral artery occlusion/reperfusion (MCAO/R) model, pcDNA-TUG1 together with miR-340-5p agomir were administrated in vivo. Furthermore, the neurologic defects in rats were assessed by a modified neurological severity score. Moreover, 2,3,5-Triphenyl-2 H-tetrazolium chloride stain-step was performed to determine the brain's infarct size. In addition, western blotting, immunohistochemistry, and qRT-PCR experiments were utilized for gauging the proteomic/genomic expression-profiles. Luciferase reporter assay validated correlations across TUG1, miR-340-5p, together with PTEN. The results indicated relatively reduced miR-340-5p levels in MCAO/R models, while upregulated TUG1 levels. The pcDNA-TUG1-treated rats indicated increasing neurological dysfunction, whereas the miR-340-5p agomir-treated rats showed improvement. Furthermore, miR-340-5p was determined to be the expected and confirmed TUG1 target. All things considered, the findings suggested that PTEN can serve as the target of miR-340-5p. In addition, TUG1 served as a miR-340-5p ceRNA, which promotes PTEN modulation. Furthermore, TUG1 overexpression decreased miR-340-5p's capacity to fend against CIRI. Conclusively, this work proved that in CIRI, targeting the TUG1/miR-340-5p/PTEN regulatory axis is a viable approach for the treatment of ischemic stroke.

Abrasivity database of different genetic rocks based on CERCHAR Abrasivity Test.

Rock abrasivity is one of the main factors affecting the wear of rock-cutting tools, which is usually quantified by the CERCHAR Abrasivity Index (CAI). Researchers and engineers study tool wear and predict tool life based on the CAI of rocks. However, there is still a lack of a dataset on rock properties, especially the abrasivity of various rocks. This paper reports the abrasive dataset of 10 kinds of rocks, including sedimentary rocks, metamorphic rocks, and igneous rocks, with the aid of the CERCHAR Abrasivity Test and digital measurement techniques. The dataset comprises rock abrasivity data, point cloud data for visualization, scratch photos, CERCHAR Abrasivity Test force data, and mechanical properties (uniaxial compressive strength) of rock samples. This dataset facilitates future research on rock abrasivity and rock-cutting tool wear.

Targeting ferroptosis opens new avenues in gliomas.

Gliomas are one of the most challenging tumors to treat due to their malignant phenotype, brain parenchymal infiltration, intratumoral heterogeneity, and immunosuppressive microenvironment, resulting in a high recurrence rate and dismal five-year survival rate. The current standard therapies, including maximum tumor resection, chemotherapy with temozolomide, and radiotherapy, have exhibited limited efficacy, which is caused partially by the resistance of tumor cell death. Recent studies have revealed that ferroptosis, a newly defined programmed cell death (PCD), plays a crucial role in the occurrence and progression of gliomas and significantly affects the efficacy of various treatments, representing a promising therapeutic strategy. In this review, we provide a comprehensive overview of the latest progress in ferroptosis, its involvement and regulation in the pathophysiological process of gliomas, various treatment hotspots, the existing obstacles, and future directions worth investigating. Our review sheds light on providing novel insights into manipulating ferroptosis to provide potential targets and strategies of glioma treatment.

Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-ß in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a significantly malignant and lethal brain tumor with an average survival time of less than 12 months. Several researches had shown that Claudin-3 (CLDN3) is overexpressed in various cancers and might be important in their growth and spread. In this study, we used qRT-PCR, western blotting, immunohistochemistry, and immunofluorescence staining assays to investigate the expression levels of various proteins. To explore the proliferation abilities of GBM cells, we conducted the CCK-8 and EdU-DNA formation assays. Wound healing and transwell assays were used to investigate the capacities of invasion and migration of GBM cells. Additionally, we constructed an intracranial xenograft model of GBM to study the in vivo role of CLDN3. Our study devoted to investigate the function of CLDN3 in the pathogenesis and progression of GBM. Our study revealed that CLDN3 was upregulated in GBM and could stimulate tumor cell growth and epithelial-mesenchymal transition (EMT) in both laboratory and animal models. We also discovered that CLDN3 expression could be triggered by transforming growth factor-ß (TGF-ß) and reduced by specific inhibitors of the TGF-ß signaling pathway, such as ITD-1. Further analysis revealed that increased CLDN3 levels enhanced TGF-ß-induced growth and EMT in GBM cells, while reducing CLDN3 levels weakened these effects. Our study demonstrated the function of CLDN3 in facilitating GBM growth and metastasis and indicated its involvement in the tumorigenic effects of TGF-ß. Developing specific inhibitors of CLDN3 might, therefore, represent a promising new approach for treating this devastating disease.

In-situ composite microstructure formation of immiscible alloy solidified in space.

The immiscible alloy Ti-Co-Gd is solidified in space by using the Electrostatic Levitation Device on board the Chinese Space Station. A sample with in-situ composite structure is obtained. The microstructure formation and gravity effect are discussed.

TUG1 aggravates intracerebral hemorrhage injury by inhibiting angiogenesis in an miR-26a-dependent manner.

Long non-coding RNA taurine-upregulated gene 1 (TUG1) plays pivotal roles in angiogenesis, an important mechanism of neural repair after intracerebral hemorrhage (ICH). However, the role of TUG1 in angiogenesis following ICH is not clear. Therefore, in this study, we investigated the role and the underlying mechanism of TUG1 in neurologic impairment and cerebral angiogenesis following ICH. The ICH rat model was established and then rats were injected with TUG1-expressing plasmid (pcDNA-TUG1) or miR-26a mimic, a critical regulator of VEGF-mediated angiogenesis. We confirmed the overexpression of TUG1 and miR-26a by qRT-PCR. The neurological deficits of ICH rats were evaluated by modified neurological severity scores. The expression of angiogenesis markers VEGF and CD31 were examined by immunohistochemistry and western blot. The interaction between TUG1 and miR-26a was determined by luciferase reporter assay. Our results showed that ICH caused a marked upregulation of TUG1 and a significant downregulation of miR-26a. TUG1 overexpression led to the deterioration of neurologic function and inhibited cerebral angiogenesis in ICH rats. In contrast, overexpression of miR-26a alleviated the neurologic damage and promoted cerebral angiogenesis in ICH rats, but these could be attenuated by TUG1 overexpression. Furthermore, TUG1 directly bound to miR-26a and inhibited its expression. Importantly, TUG1 overexpression inhibited the expression of VEGF by targeting miR-26a. In conclusion, our results indicated that TUG1 aggravated ICH-mediated injury by suppressing angiogenesis by downregulating miR-26a. This suggests a rationale for targeting TUG1/miR-26a in the therapy of ICH.

Essential genes Ptgs2, Tlr4, and Ccr2 regulate neuro-inflammation during the acute phase of cerebral ischemic in mice.

Ischemic stroke (IS) is associated with changes in gene expression patterns in the ischemic penumbra and extensive neurovascular inflammation. However, the key molecules related to the inflammatory response in the acute phase of IS remain unclear. To address this knowledge gap, conducted a study using Gene Set Enrichment Analysis (GSEA) on two gene expression profiles, GSE58720 and GSE202659, downloaded from the GEO database. We screened differentially expressed genes (DEGs) using GEO2R and analyzed 170 differentially expressed intersection genes for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. We also used Metascape, DAVID, STRING, Cytoscape, and TargetScan to identify candidate miRNAs and genes. The targeted genes and miRNA molecule were clarified using the mice middle cerebral artery occlusion-reperfusion (MCAO/R) model. Our findings revealed that 170 genes were correlated with cytokine production and inflammatory cell activation, as determined by GO and KEGG analyses. Cluster analysis identified 11 hub genes highly associated with neuroinflammation: Ccl7, Tnf, Ccl4, Timp1, Ccl3, Ccr1, Sele, Ccr2, Tlr4, Ptgs2, and Il6. TargetScan results suggested that Ptgs2, Tlr4, and Ccr2 might be regulated by miR-202-3p. In the MCAO/R model, the level of miR-202-3p decreased, while the levels of Ptgs2, Tlr4, and Ccr2 increased compared to the sham group. Knockdown of miR-202-3p exacerbated ischemic reperfusion injury (IRI) through neuroinflammation both in vivo and in vitro. Our study also demonstrated that mRNA and protein levels of Ptgs2, Tlr4, and Ccr2 increased in the MCAO/R model with miR-202-3p knockdown. These findings suggest that differentially expressed genes, including Ptgs2, Tlr4, and Ccr2 may play crucial roles in the neuroinflammation of IS, and their expression may be negatively regulated by miR-202-3p. Our study provides new insights into the regulation of neuroinflammation in IS.

Curcumin protects from LPS-induced activation of astrocytes via AMPK pathway.

Curcumin, a phenolic pigment, plays an inhibitory role in astrocytes activation which are involved in the pathogenesis of neurological diseases and inflammatory responses. The present study aimed to investigate the underlying regulatory mechanism behind the therapeutic effect of curcumin on the lipopolysaccharide (LPS)-activated astrocytes in vitro. Specifically, we investigated the inhibitory effect of curcumin on LPS-induced astrocyte's proliferation. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that curcumin significantly increased the level of phosphorylated AMPK protein in LPS-activated astrocytes. In addition, our data demonstrated that curcumin play an inhibitory role on the migration, autophagy, the pro-inflammatory mediators by the AMPK signaling pathway in LPS-activated astrocytes. These results could shed light on understanding of molecular mechanism for the inhibition of curcumin on migration, autophagy, and the pro-inflammatory mediators during the process of astrocyte activation, and might contribute to a promising therapeutic intervention in the neurological diseases-related astrocytes activation.

The rock damage mechanism of combined rock breaking with saw blade and conical pick.

The combined rock breaking method with the saw blade and conical pick is proposed to improve the rock breaking efficiency. The numerical simulation of combined rock breaking with the saw blade and conical pick is established to investigate the rock damage mechanism. And verified and modified the numerical simulation model with the rock breaking comprehensive test bench, the quantitative analysis error is less than 0.05, indicated quantitative analysis system is accuracy. The result indicated that the cutting parameters of the saw blade and conical pick affect the rock damage. And the cutting parameters of conical pick and structural parameters of rock plate have been studied to influence rock breaking volume. The research result could help optimize the cutting parameters of the saw blade and conical pick to improve the rock breaking efficiency.

The mechanism and performance of rock breakage by undercutting disc cutter with advanced slotting.

To study the mechanism and performance of rock breakage by an undercutting disc cutter with advanced slotting, a three-dimensional numerical model of rock cutting by a disc cutter with advanced slotting assistance was established based on the discrete element method. The parallel bond constitutive model was selected to describe the micromechanical properties of rock. The correctness of the established numerical model is verified through rock breakage experiments, and the rock cutting process by the disc cutter was analyzed by a combination of the force chain and crack distribution. The influencing factors, such as advanced slotting depth, cutting thickness, rock strength, and cutter rotation speed, on rock cutting performance were investigated. The results show that a compact zone is gradually formed between the rock and disc cutter at the beginning, then a large number of microscopic tensile and shear cracks in the compact zone due to micro failure of rock are formed; the subsequent main rock fragment is mainly caused by tensile failure; advanced slotting can reduce the rock bearing capacity and bending resistance, the rock above the advanced slotting fractured easily due to its lower bending resistance, and the volume compact zone is relatively small. When the advanced slotting depth is equal to 12.5 mm, the propulsive force and specific energy consumption of rock cutting by the disc cutter are reduced by 61.6% and 16.5%, respectively. The propulsive force and specific energy consumption increase as the rock strength increases, but they tend to close when the rock strength is greater than 80 MPa, which indicates that advanced slotting assistance is more suitable for hard rock. The results obtained in this paper can provide the operating parameters determination under different factors to some extent of the undercutting disc cutter in a pre-cut condition, which further improve the rock breaking performance of mechanized cutter.

Accurate integrated position measurement system for mobile applications in GPS-denied coal mine.

The automatic positioning of underground mobile applications plays a crucial role in enabling intelligent coal mining. However, due to the diverse kinematics and dynamics of these applications, various positioning methods have been proposed to match different targets. Nonetheless, the accuracy and applicability of these methods still fall short of meeting the requirements for field applications. Based on the vibration characteristics of underground mobile devices, a multi-sensor fusion positioning system is developed to enhance the accuracy of positioning in long and narrow global positioning system denied (GPS-denied) underground coal mine roadways. The system combines inertial navigation (INS), odometer, and ultra wide band (UWB) technologies through extended Kalman filter (EKF) and unscented Kalman filter (UKF). This approach enables accurate positioning by recognizing target carrier vibrations and facilitating fast conversion between multi-sensor fusion modes. The proposed system is tested on both a small unmanned mine vehicle (UMV) and a large roadheader, demonstrating that UKF enhances stability for roadheaders with strong nonlinear vibrations while EKF is more suitable for flexible UMVs. Detailed results confirm that the proposed system achieves an accuracy level of 0.15 m, meeting most coal mine application requirements.

[Corrigendum] HHLA2 is a novel prognostic predictor and potential therapeutic target in malignant glioma.

Following the publication of this article, an interested reader drew to the authors' attention that, in Fig. 1F on p. 2311 showing a representative high­grade glioma specimen, the data were either duplicated or overlapping with the data featured in Fig. 1D, which showed a low­grade glioma specimen. After having consulted their original data, the authors have realized that the data for Fig. 1D were inadvertently selected incorrectly. The corrected version of Fig. 1, now showing the correct data for the high­magnification high­grade glioma specimen in Fig. 1F, is shown on the next page. The authors sincerely apologize for the error that was introduced during the preparation of this figure, thank the Editor of Oncology Reports for granting them the opportunity to publish a Corrigendum, and are grateful to the reader for alerting them to this issue. The authors also regret any inconvenience that this mistake may have caused. [Oncology Reports 42: 2309-2322, 2019; DOI: 10.3892/or.2019.7343].