Search

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.

Fenoxaprop-P-ethyl (FE) can effectively control weeds in rice fields, but it has been found to cause phytotoxicity in rice. In this study, the phytotoxicity of FE was mitigated by perilla leaf essential oil (PEO) in rice seedlings. The injury recovery rates (IRRs) for shoot length and fresh weight treated with 800 mg/L of PEO were 101.51% and 99.05%, respectively. Moreover, the damage of s-metolachlor and pretilachlor was also alleviated when co-applied with 800 mg/L PEO; the IRR of s-metolachlor phytotoxicity was 26.07% and 27.34%, respectively, and the IRR of pretilachlor phytotoxicity was 127.27% and 124.39%, respectively. However, PEO had no significant effect on the phytotoxicity of pinoxaden, mesotrione, penoxsulam, mesosulfuron-methyl, and nicosulfuron. The results of GC–MS analysis showed that a total of 23 components were detected in PEO, among which linalool (36.49%), linalyl formate (26.96%), α-terpineol (10.63%), 2-hexanoylfuran (5.81%), geranyl acetate (4.13%), and neryl acetate (2.30%) were the primary components. Among them, 2-hexanoylfuran was the most effective component to alleviate FE damage, for which the IRR of shoot length and fresh weight was 73.17% and 73.02%, respectively, followed by the geranyl acetate, for which the IRR was 72.32% and 60.56%, respectively, and neryl acetate, for which the IRR was 65.28% and 58.11%, respectively. Furthermore, the application of 50 mg/L of 2-hexanofuran significantly improved the tolerance of shoot length and fresh weight to FE stress by factors of 5.32 and 5.35, respectively. This research demonstrates that PEO and 2-hexanoylfuran have the potential to serve as natural safeners to reduce phytotoxicity. [ABSTRACT FROM AUTHOR]

Stress interference is the main factor affecting hydraulic fracture propagation during multi-well hydraulic fracturing; stress interference is influenced by fracture bending, fracture hits, and asymmetric fracture propagation. To investigate the role of stress interferences among hydraulic fractures with nonuniform stress distribution in an inhomogeneous formation, a hydromechanical coupling extended finite element method was adopted to investigate the fracturing paths that occurred during the first fracturing–fracturing fluid flowback–repeat fracturing process; the asymmetric fracturing that occurred at different child well locations was also studied. The results showed that the area affected by fracturing-induced stress formed a "butterfly type" area. For child wells located within the zone, stress interference resulted in asymmetric fracture propagation; meanwhile, for child wells located outside this zone, stress interference resulted in symmetric fracture geometry. The effect of stress interference on the asymmetry of child well fracture wings was found to be negatively correlated with the distance between the parent well and the child well. [ABSTRACT FROM AUTHOR]

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]