Parameter design and effectiveness evaluation of wide strip mining of extra thick coal seams under dense buildings.

In order to safeguard the surface structures from mining damage while optimizing the liberation of coal resources under the dense surface buildings of the Cedi River coal mine. Considering that the analysis of the structure and type of surface buildings and the geological mining conditions of the mine, a wide strip mining design with a retention width of 70 m and a mining width of 50 m was finally determined by using the pressure arch theory and Wilson's theory, combined with the actual layout of working faces 51,002, 51,004 and 51,006 at the site.The strip mining design is verified by probability integral method and FLAC3D numerical simulation calculation respectively, The findings indicate that the highest value of earth surface subsidence created by the mining of the wide strip is 210 mm, the surface horizontal deformation value is 1.0 to - 1.4 mm/m, the damage to surface buildings is less than Level I, which satisfying the prerequisites of the surface building protection level, and can realize the continuous advancement of mine 51,002, 51,004 and 51,006 working faces, The coal pillars of the retained strip have sufficient support strength and long-term consistency, and the movement and deformation of the overburden after mining will not cause undulating subsidence of the surface, which effectively solve the mine's technical difficulties in safely coal mining under surface buildings.

"Before Dawn," Listening to the Voices of Social Media: A Study on the Public's Response to the COVID-19 Vaccine.

The COVID-19 pandemic is a worldwide catastrophe. In the absence of an effective drug, one effective measure to pull the pandemic to the end is herd immunity by taking vaccines, while the hesitation and anti-attitude from social media affect the vaccination. This makes it crucial to evaluate the text data about the COVID-19 vaccine from tweets. The period for data used in this study is 1 Aug to 31 Oct, 2020, since it is just before promoting the use when public reactions to the COVID-19 vaccine can influence their subsequent vaccination behavior. In this study, we used the latent Dirichlet allocation (LDA) topic model and sentiment analysis to explore public reactions to the COVID-19 vaccine. The results indicate that the public discussion could be divided into 11 topics, which could be further summarized into four different themes: (1) concerns about COVID-19; (2) concerns about vaccine development, production, and distribution; (3) how to control the COVID-19 before obtaining the vaccine; and (4) concerns about information of vaccine safety and efficacy. It can be concluded that to a large extent, public reactions to vaccines are dominated by positive sentiment. Specifically, the politicization of the vaccine approval process, suspension of vaccine trials, and measures to control COVID-19 tend to trigger negative public sentiment; whereas information related to successful vaccine development and availability enhances positive public sentiment. These findings help us understand public reactions to the COVID-19 vaccine, uncover potential factors that may influence vaccination behavior, and help policymakers understand public opinion about the COVID-19 vaccine and develop rational and effective policies.

Design, Fabrication, and Mechanical Properties of T-700TM Multiaxial-Warp-Knitting-Needled-C/SiC Composite and Pin.

In this paper, the 12k T-700TM Multiaxial-Warp-Knitting-Needle (MWK-N) C/SiC composite and pin were designed and fabricated using the isothermal chemical vapor infiltration (ICVI) method. The composite's microstructure and mechanical properties were examined by subjection to tensile and interlaminar shear tests. Three types of double-shear tests were conducted for C/SiC pins, including shear loading perpendicularly, along, and at 45° off-axial to the lamination. The fracture surface of the tensile and shear failure specimens was observed under scanning electronic microscope (SEM). The relationships between the composite's microstructure, mechanical properties, and damage mechanisms were established. The composite's average tensile strength was σuts = 68.3 MPa and the average interlaminar shear strength was τu = 38.7 MPa. For MWK-N-C/SiC pins, the double-shear strength was τu = 76.5 MPa, 99.7 MPa, and 79.6 MPa for test types I, II, and III, respectively. Compared with MWK-C/SiC pins, the double-shear strength of MWK-N-C/SiC pins all decreased, i.e., 26.7%, 50.8%, and 8% for test types I, II, and III, respectively. The MWK-N-C/SiC composite and pins possessed high interlaminar shear strength and double-shear strength, due to the needled fiber in the thickness direction, low porosity (10-15%), and high composite density (2.0 g/cm3).

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy.

BACKGROUND: The poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity. METHODS: The antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy. RESULTS: USNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment. CONCLUSION: The administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.

ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation.

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis.

BACKGROUND: Angiogenesis is a critical step in the growth of pancreatic neuroendocrine tumors (PNETs) and may be a selective target for PNET therapy. However, PNETs are robustly resistant to current anti-angiogenic therapies that primarily target the VEGFR pathway. Thus, the mechanism of PNET angiogenesis urgently needs to be clarified. METHODS: Dataset analysis was used to identify angiogenesis-related genes in PNETs. Immunohistochemistry was performed to determine the relationship among Neuropilin 2 (NRP2), VEGFR2 and CD31. Cell proliferation, wound-healing and tube formation assays were performed to clarify the function of NRP2 in angiogenesis. The mechanism involved in NRP2-induced angiogenesis was detected by constructing plasmids with mutant variants and performing Western blot, and immunofluorescence assays. A mouse model was used to evaluate the effect of the NRP2 antibody in vivo, and clinical data were collected from patient records to verify the association between NRP2 and patient prognosis. RESULTS: NRP2, a VEGFR2 co-receptor, was positively correlated with vascularity but not with VEGFR2 in PNET tissues. NRP2 promoted the migration of human umbilical vein endothelial cells (HUVECs) cultured in the presence of conditioned medium PNET cells via a VEGF/VEGFR2-independent pathway. Moreover, NRP2 induced F-actin polymerization by activating the actin-binding protein cofilin. Cofilin phosphatase slingshot-1 (SSH1) was highly expressed in NRP2-activating cofilin, and silencing SSH1 ameliorated NRP2-activated HUVEC migration and F-actin polymerization. Furthermore, blocking NRP2 in vivo suppressed PNET angiogenesis and tumor growth. Finally, elevated NRP2 expression was associated with poor prognosis in PNET patients. CONCLUSION: Vascular NRP2 promotes PNET angiogenesis by activating the SSH1/cofilin/actin axis. Our findings demonstrate that NRP2 is an important regulator of angiogenesis and a potential therapeutic target of anti-angiogenesis therapy for PNET.

Overexpression of Nogo receptor 3 (NgR3) correlates with poor prognosis and contributes to the migration of epithelial cells of nasopharyngeal carcinoma patients.

Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines. Among these genes, Nogo receptor 3 (NgR3), which was originally identified in the nervous system and plays a role in nerve development and regeneration, was inappropriately overexpressed in NPC cells and tissues. Immunohistochemical analysis demonstrated that the overexpression of NgR3 was correlated with poor prognosis in NPC patients. Overexpression of NgR3 promoted, and knocking down NgR3 inhibited, NPC cell migration and invasion in vitro and metastasis in vivo. The ability of NgR3 to promote cell migration was triggered by the downregulation of E-cadherin and enhanced cytoskeletal rearrangement and cell polarity, which were correlated with the activation of focal adhesion kinase (FAK). Collectively, NgR3 is a novel indicator of poor outcomes in NPC patients and plays an important role in driving the progression of NPC. These results suggest a potential link between the nervous system and NPC progression. KEY MESSAGES: Genes involved in the neuronal biological process are enriched in nasopharyngeal carcinoma. Overexpression of NgR3 correlates with poor prognosis of nasopharyngeal carcinoma. NgR3 promotes NPC cell migration by downregulating E-cadherin. NgR3 promotes NPC cell polarity and enhances the formation of NPC cell pseudopodia by activating FAK/Src pathway.

Author Correction: Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.

In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl benzoic acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl benzoic acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl benzoic acid derivative. All references to 2,5-dimethylpyrrolyl benzoic acid in the Letter have now been changed to reflect this.Although 2,5-dimethylpyrrolyl benzoic acid derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein-Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.

Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.

Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR-Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl benzoic acid efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi's sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.