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Characterizing changes in rock properties is essential for the hydraulic fracture and re-fracture parameter optimization of shale formations. This paper proposed a hydraulic fracturing model to investigate the changes in rock properties during hydraulic fracturing using SPH, and the changes in the stress field and rock properties were quantitatively characterized. The simulation results indicated that the minimum horizontal principal stress increased by 10 MPa~15 MPa during fracture propagation, which is the main reason for the uneven propagation in multi-fracture propagation. Affected by the stress disturbance, the stimulated area was divided into four parts based on the changes in Young's modulus and permeability; the more seriously the stress disturbance was affected, the higher the permeability of the stimulated zone was, and the smaller the stimulated zone was. Meanwhile, a zone with reduced permeability appeared due to the compression effect caused by the high injection pressure, and this increased with the increase in stress disturbance. The main reason for this was that strain formed because of the compression effect from the high injection pressure. The higher the stress disturbance, the higher the accumulated strain. This new model provides a new method for fracture parameter optimization, which also provides a foundation for the re-fracture parameter optimization of shale formations. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies to maximize therapeutic benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. 90% of treated patients achieved complete remission, underscoring the potential of this regimen as a compelling therapeutic intervention. To elucidate underlying mechanisms governing response to DAV in AML, quantitative phosphoproteomics to discern distinct molecular signatures characterizing a subset of DAV‐sensitive patients is used. Cluster analysis reveals an enrichment of phosphoproteins implicated in chromatin organization and RNA processing within DAV‐susceptible and DA‐resistant AML patients. Furthermore, kinase activity profiling identifies AURKB as a candidate indicator of DAV regimen efficacy in DA‐resistant AML due to AURKB activation. Intriguingly, AML cells overexpressing AURKB exhibit attenuated MCL‐1 expression, rendering them receptive to DAV treatment and maintaining them resistant to DA treatment. Moreover, the dataset delineates a shared kinase, AKT1, associated with DAV response. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML. [ABSTRACT FROM AUTHOR]

The virtual teaching and research platform is a cognitive and practical activity for relevant teachers engaged in education and teaching research to improve and improve the quality of education and teaching, relying on the unique functions and resource advantages of the network, using information technology and various network tools to carry out teaching, feedback, etc., and to carry out education and teaching exchange, discussion and other education and teaching research with other administrative organizations or teachers in space regions. It can break the constraints of time, space, organization and other factors. It is an effective form of educational and teaching activities carried out for common goals. It integrates teaching, guidance, discussion, exchange, resource sharing and other functions, and is an important part of the "double training plan". The collaborative innovation ability training mode selection of virtual teaching and research platforms as a multi-attribute group decision making (MAGDM) problem. In this paper, the Evaluation Based on Distance from Average Solution (EDAS) method is extended to the single-valued neutrosophic sets (SVNSs) and single-valued neutrosophic EDAS method (SVN-EDAS) is proposed to solve MAGDM problem. Finally, the collaborative innovation ability training mode selection of virtual teaching and research platforms is given to show the SVN-EDAS model and some comparative analysis is conduct to depict the advantages of SVN-EDAS. [ABSTRACT FROM AUTHOR]

(J) ChIP-qPCR assay in 293T cells that ectopically overexpress Flag-tagged HMGA1-WT or HMGA1-S3A, and with siSP1 in these Flag-HMGA1 expressing cells. (B) Western blotting for pan-phospho-serine levels in 293T cells transduced with MOCK, Flag-tagged HMGA1-WT, HMGA1-S99A, HMGA1-S102A, HMGA1-S103A or HMGA1-S3A. ChIP analysis using anti-flag antibodies or control normal mouse IgG was performed in four groups: HMGA1-WT/siCtrl, HMGA1-WT/siSP1, HMGA1-S3A/siCtrl and HMGA1-S3A/siSP1. [Extracted from the article]

Background: Long non-coding RNA (lncRNA) plays an essential regulatory role in the occurrence and development of hepatocellular carcinoma (HCC). This paper aims to establish an immune-related lncRNA (irlncRNA) pairs model independent of expression level for risk assessment and prognosis prediction of HCC. Methods: Transcriptome data and corresponding clinical data were downloaded from TCGA. HCC patients were randomly divided into training group and test group. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multiple Cox regression analysis were used to establish a prognostic model. The prediction ability of the model was verified by ROC curves. Next, the patients were divided into low-risk and high-risk groups. We compared the differences between the two groups in survival rate, clinicopathological characteristics, tumor immune cell infiltration status, chemotherapeutic drug sensitivity and immunosuppressive molecules. Results: A prognosis prediction model was established based on 7 irlncRNA pairs, namely irlncRNA pairs (IRLP). ROC curves of the training group and test group showed that the IRLP model had high sensitivity and specificity for survival prediction. Kaplan–Meier analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Immune cell infiltration analysis showed that the high-risk group was significantly correlated with various immune cell infiltration. Finally, there were statistically significant differences in chemosensitivity and molecular marker expression between the two groups. Conclusion: The prognosis prediction model established by irlncRNA pairs has a certain guiding significance for the prognosis prediction of HCC. It may provide valuable clinical applications in antitumor immunotherapy. [ABSTRACT FROM AUTHOR]

The serine protease inhibitor clade E member 1 (SERPINE1) is a major inhibitor of tissue plasminogen activator and urokinase, and has been implicated in the development and progression of a variety of tumors. In this study, mRNA microarray and TCGA database were used to comprehensively analyze the upregulation of SERPINE1 in gastric cancer (GC) tissues compared with the normal stomach tissues. Kaplan-Meier results confirmed that patients with high SERPINE1 expression exhibited worse overall survival and disease-free survival. In addition, cell proliferation, cell scratches, transwell migration and invasion assay showed that SERPINE1 knockdown inhibited the proliferation, migration and invasion of GC ells. Western blot showed that the expression of VEGF and IL-6 was significantly upregulated after overexpression of SERPINE1. Meanwhile, SERPINE1 was positively correlated with the level of immune infiltration using the online analysis tools TISIDB and TIMER. And SERPINE1 expression increased with the increase of malignancy of GC which were detected by Immunohistochemistry. Finally, tumorigenesis experiments in nude mice further demonstrated that SERPINE1 could promote the occurrence and development of GC, while deletion of SERPINE1 inhibited the progression of GC. In summary, SERPINE1 was highly expressed in GC tissues, and SERPINE1 was helpful for differential diagnosis of pathological grade of gastric mucosal lesions. SERPINE1 might regulate the expression of VEGF and IL-6 through the VEGF signaling pathway and JAK-STAT3 inflammatory signaling pathway, thus ultimately affecting the invasion and migration of GC cells. [ABSTRACT FROM AUTHOR]

The cementitious composites with microencapsulated healing agents have become a class of hotspots in the field of construction materials, and they have very broad application prospects and research values. The in-depth study on multi-scale mechanical behaviors of microencapsulated self-healing cementitious composites is critical to quantitatively account for the mechanical response during the damage-healing process. This paper proposes a three-dimensional evolutionary micromechanical model to quantitatively explain the self-healing effects of microencapsulated healing agents on the damage induced by microcracks. By virtue of the proposed 3 D micromechanical model, the evolutionary domains of microcrack growth (DMG) and corresponding compliances of the initial, extended and repaired phases are obtained. Moreover, the elaborate studies are conducted to inspect the effects of various system parameters involving the healing efficiency, fracture toughness and preloading-induced damage degrees on the compliances and stress-strain relations. The results indicate that relatively significant healing efficiency, preloading-induced damage degree and the fracture toughness of polymerized healing agent with the matrix will lead to a higher compressive strength and stiffness. However, the specimen will break owing to the nucleated microcracks rather than the repaired kinked microcracks. Further, excessive higher values of healing efficiency, preloading-induced damage degree and the fracture toughness of polymerized healing agent with the matrix will not affect the compressive strength of the cementitious composites. Therefore, a stronger matrix is required. To achieve the desired healing effects, the specific parameters of both the matrix and microcapsules should be selected prudently. [ABSTRACT FROM AUTHOR]

Abstract Background We previously found that r-hu-IFNγ exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts in vivo. Considering the fact that the clinical use of recombinant IFNγ is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFNγ. Methods Dynamic distribution of the adenovirus vector and expression of IFNγ were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFNγ into CNE-2 xenografts. Results Ad-IFNγ DNA was mainly enriched in tumors where the Ad-IFNγ DNA was injected (P < 0.05, compared to blood or parenchymal organs), as well as in livers (P < 0.05). Concentrations of Ad-IFNγ DNA in other organs and blood were very low. Intratumoral Ad-IFNγ DNA decreased sharply at high concentrations (9 × 105 copies/μg tissue DNA), and slowly at lower concentrations (1.7–2.9 × 105 copies/μg tissue DNA). IFNγ was detected in the tumors and parenchymal organs. The concentration of IFNγ was highest in the tumor (P < 0.05), followed by the liver and kidney (P < 0.05). High-level intratumoral expression of IFNγ was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFNγ DNA. Conclusion An IFNγ gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFNγ DNA and the transgene product were mainly enriched in the liver.

Objective: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). Methods: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. Results: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. Conclusion: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery. [ABSTRACT FROM AUTHOR]

Lack of training samples always affects the performance and robustness of face recognition. Generating virtual samples is one of effective methods to expand the training set. When the virtual samples are able to simulate the variations of facial images including variations of illuminations, facial postures and the facial expressions, the robustness will be enhanced and the accuracy will be improved obviously in the face recognition problem. In this paper, an improved linear representation-based classification combined virtual samples (ILRCVS) is proposed. First, we design a new objective function that simultaneously considers the information of the virtual training samples and the virtual test sample. Second, an alternating minimization algorithm is proposed to solve the optimization problem of the objective function. Finally, a new classification criterion combined with the virtual training and test sample is proposed. Experimental results on the Georgia Tech, FERET and Yale B face databases show that the proposed method is more robust than three state-of-the-art face recognition methods, LRC, SRC and CRC. [ABSTRACT FROM AUTHOR]

Oxidative stress is thought to contribute to cancer development. Epstein–Barr virus (EBV) and its encoded oncoprotein, latent membrane protein 1 (LMP1), are closely associated with the transformation of nasopharyngeal carcinoma (NPC) and Burkitt’s lymphoma (BL). In this study, we used LMP1-transformed NP cells and EBV-related malignant cell lines to assess the effects of LMP1 on reactive oxygen species (ROS) accumulation and glycolytic activity. Using NPC tissue samples and a tissue array to address clinical implications, we report that LMP1 activates NAD(P)H oxidases to generate excessive amount of ROS in EBV-related malignant diseases. By evaluating NAD(P)H oxidase (NOX) subunit expression, we found that the expression of the NAD(P)H oxidase regulatory subunit p22phox was significantly upregulated upon LMP1-induced transformation. Furthermore, this upregulation was mediated by the c-Jun N-terminal kinase (JNK) pathway. In addition, LMP1 markedly stimulated anaerobic glycolytic activity through the PI3K/Akt pathway. Additionally, in both NPC cells and tissue samples, p22phox expression correlated with LMP1 expression. The NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI) also exerted a marked cytotoxic effect in LMP1-transformed and malignant cells, providing a novel strategy for anticancer therapy. [ABSTRACT FROM AUTHOR]

Lycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes. However, the underlying mechanisms of its hepatic-protective properties remain uncertain. In this study, we aimed to investigate whether thioredoxin-interacting protein (TXNIP) and NOD-like receptor 3 (NLRP3) inflammasome mediated the attenuation of ethanol-induced hepatic injury by Lycium barbarum polysaccharide (LBP). Rat normal hepatocyte line BRL-3A was pre-treated with LBP prior to ethanol incubation. Hepatic damages, including apoptosis, inflammation, and oxidative stress, were measured. Then the inhibition of endogenous TXNIP expression was achieved by using its specific siRNA to test its possible involvement in the injury attenuation. We found that 50 μg/ml LBP pre-treatment significantly alleviated 24-h ethanol exposure-induced overexpression of TXNIP, increased cellular apoptosis, secretion of inflammatory cytokines, activation of NLRP3 inflammasome, production of ROS, and reduced antioxidant enzyme expression. Silence of TXNIP suppressed the activated NLRP3 inflammasome, increased oxidative stress and worsened apoptosis in the cells. Further addition of LBP did not influence the effects of TXNIP inhibition on the cells. In conclusion, inhibition of hepatic TXNIP by LBP contributes to the reduction of cellular apoptosis, oxidative stress and NLRP3 inflammasome-mediated inflammation. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an endemic malignant disease of the head and neck region with unique features including striking ethnic and geographic variations as well as multifactorial etiology. Previous studies have demonstrated the anticancer properties of genistein, the major soy isoflavonoid, in several human cancer cells such as breast, prostate, colon, gastric, lung, and hepatoma. However, the action of genistein in NPC cells has not been determined. In this study, we investigated the inhibitory effects of genistein on NPC cells and its possible underlying mechanisms. We found that genistein dose-dependently inhibited the proliferation of human NPC cell line CNE2 cells. DNA flow cytometric analysis revealed that 30 to 120 μM genistein induced dramatic G2/M phase arrest in NPC cells. The mRNA expression levels, as shown by gene expression array and quantitative real-time polymerase chain reaction, and the protein expression levels of the cell cycle regulators p21Cip1 and ATR (Ataxia telangiectasia and Rad3 related) were elevated following genistein treatment. Interestingly, we also observed concomitant induction of p15Ink4b in genistein induced inhibitory effects in NPC cells. Moreover, selective estrogen receptor modulators did not affect genistein induced growth inhibition. These findings provide new insights into the potential intervention of NPC with genistein. [ABSTRACT FROM AUTHOR]

Background & Aims Levels of atonal homolog 8 ( ATOH8 ) are reduced in 48% of hepatitis B virus-associated hepatocellular carcinoma cells (HCCs). ATOH8 downregulation is associated with loss of tumor differentiation, indicating an effect mediated by cancer stem cells. We investigated the effects of loss of ATOH8 in human hepatocellular carcinoma (HCC) cells and cell lines. Methods HCC and adjacent nontumor tissues were collected, from 2001 through 2012, from 242 patients undergoing hepatectomy at Sun Yat-Sen University Cancer Center in China; 83% of HCCs were associated with hepatitis B virus (HBV) infection. CD133 + cells were isolated from tumor tissues by flow cytometry. Experiments were performed in HBV-positive and HBV-negative HCC cell lines, the immortalized liver cell line LO2, and 8 other HCC cell lines. ATOH8 was expressed from lentiviral vectors in PLC8024 and Huh7 cells; levels were knocked down with small interfering RNAs in QSG7701 cells. Cells carrying empty vectors were used as controls. Gene regulation by ATOH8 was assessed in mobility shift and luciferase reporter assays. Cells were analyzed in proliferation, foci formation, and colony formation assays. The tumorigenic and chemo-resistant potential of cells were investigated by assessing growth of xenograft tumors in immunocompromised mice. Metastatic features of cells were assessed in Matrigel invasion assays and wound healing analyses. Results Levels of ATOH8 mRNA were reduced by more than 4-fold, compared to nontumor tissues, in 118 of 242 HCC samples (48.8%). Patients with tumor reductions in ATOH8 had significantly shorter times of disease-free survival (mean, 41.4 months) than patients with normal tissue levels (mean, 52.6 months). ATOH8 expression was reduced in HepG2, Huh7, PLC8024 and CRL8064 HCC cells, as well as CD133 + cells isolated from human HCC samples. Transgenic expression of ATOH8 in HCC cell lines significantly reduced proliferation and foci colony formation, as well as their invasive and migratory abilities. Transgenic expression of ATOH8 reduced the ability of HBV-positive PLC8024 cells to form tumors in mice, compared to control cells. Cells with ATOH8 knockdown formed xenograft tumors more rapidly, in more mice, than control cells. ATOH8 repressed transcription of stem-cell associated genes including OCT4 , NANOG , and CD133 . Knockdown of ATOH8 in CD133-negative QSG7701 cells caused them to express CD133 ; acquire self-renewal, differentiation, chemo-resistance properties; form more xenograft tumors in mice; and generate induced pluripotent stem cells (based on staining for alkaline phosphatase and their ability to form embryoid bodies and teratomas). Alternatively, expression of ATOH8 in PLC8024 and Huh7 cells significantly reduced the numbers of cells expressing CD133 , and increased the chemo-sensitivity of Huh7 cells to 5-fluorouracil (5-FU) and cisplatin, in vitro and in mice. Conclusions ATOH8 appears to be a tumor suppressor that induces stem-cell features and chemoresistance in HCC cells. Strategies to restore its levels and activities might be developed to treat patients with liver cancer. [ABSTRACT FROM AUTHOR]