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A palladium‐catalyzed inert C−H bond activation and cyclocarbonylation of isoquinolones leading to isoindolo[2,1‐b]isoquinoline‐5,7‐diones under 1 atm of carbon dioxide has been developed. This transformation features high regio‐ and chemo‐selectivity, step‐economy, and good functional group tolerance. Most of the corresponding products were obtained in moderate to good yields. It offers an alternative approach for the synthesis of useful diverse isoindolo[2,1‐b]isoquinoline‐5,7‐dione derivatives. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer stem cells (CSCs) promote pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and chemoresistance. Cyclin-dependent kinase 1 (CDK1) plays an important role in tumor initiation in other tumors, but the function of CDK1 in PDAC remains unclear. Fisetin is a bioactive flavonoid with anti-tumor properties in multiple tumors, while its function in CSCs remains elusive. Results: In this study, we demonstrated that CDK1 was correlated with prognosis and was highly expressed in pancreatic cancer tissue and gemcitabine-resistant cells. Silencing CDK1 impaired tumor stemness and reduced a subset of CSCs. We found that fisetin blocked the kinase pocket domain of CDK1 and inhibited pancreatic CSC characteristics. Using acetylation proteomics analysis and phosphorylation array assay, we confirmed that fisetin reduced CDK1 expression and increased CDK1 acetylation at lysine 33 (K33), which resulted in the suppression of CDK1 phosphorylation. Silencing CDK1 or STAT3 suppressed tumor stemness properties, while overexpressing CDK1 or STAT3 showed the opposite effect. Mutation or acetylation of CDK1 at K33 weakened STAT3 phosphorylation at Y705, impairing the expression of stem-related genes and pancreatic cancer stemness. In addition, lack of histone deacetylase 3 (HDAC3), which deacetylates CDK1, contributed to weakening STAT3 phosphorylation by regulating the post-translational modification of CDK1, thereby decreasing the stemness of PDAC. Moreover, our results revealed that fisetin enhanced the effect of gemcitabine through eliminating a subpopulation of pancreatic CSCs by inhibiting the CDK1–STAT3 axis in vitro and in vivo. Conclusion: Our findings highlight the role of post-translational modifications of CDK1–STAT3 signaling in maintaining cancer stemness of PDAC, and indicated that targeting the CDK1–STAT3 axis with inhibitors such as fisetin is a potential therapeutic strategy to diminish drug resistance and eliminate PDAC. [ABSTRACT FROM AUTHOR]

In the drilling and stimulation operations of deep/ultra-deep oil and gas wells, high in situ stress conditions may increase the occurrence probability of rock shear failures. According to Mole-Coulomb laws, the friction coefficient becomes more significant in evaluating borehole instability, faults/natural fractures activation and hydraulic-natural fractures intersection scenarios. This paper proposes a multiscale model to calculate the rock friction coefficients based on the surface properties at different scales. The key parameters of surface properties are obtained from three-dimensional laser scan of friction planes, and the results are verified by the direct shearing and triaxial compression strength tests. For the flat or new-cutting surfaces, the computed basic friction coefficients range of 0.231–0.509, fitting well with the tested values of 0.303–0.437. It also shows that the basic friction coefficients grow in the order of shale, carbonate and tight sandstone, positively associated with the size of the rock sedimentary particles. For the roughness surfaces, the coefficients are computed based on the former basic friction values and the surface asperity dip angles distribution, and the values located in a wide range of 0.541–1.113, also matched well with the measured friction coefficients via direct shearing tests. When the normal stress increase, the rock friction coefficients generally decline, and the values of some shale and dolomite samples can decrease to 0.2, due to the existence of beddings or fracture fillings. The above outcomes may provide useful insights for wellbore instability assessment and hydraulic fracturing optimization. [ABSTRACT FROM AUTHOR]

A pH‐responsive amphiphilic surfactant stearic amide 3‐(N,N‐dimethylamino)propylamide (SAA) was synthesized and served as a thickener in aqueous solution to construct a switchable viscoelastic surfactant fluid (VES fluid). The structure of SAA was studied by 1H NMR, and the viscoelastic behavior of VES fluid was studied in detail by rheological measurements. The viscosity of this VES fluid can be switched reversibly from low to high immediately by adjusting system pH value. Even at high shear rate (170 s−1) and high temperature (90 °C), excellent viscoelastic behavior of this VES fluid can be observed, which is a key performance for fracturing applications. Meanwhile, the recycled VES fluid can still maintain good pH‐responsive behavior even after more than three cycles. These unique performances of this VES fluid not only enhanced our understanding of the transformation of wormlike micelles at high temperature, but also enriched a large potential of VES fracturing fluid in the development of oil and gas reservoirs. [ABSTRACT FROM AUTHOR]

In order to mitigate the loss circulation of oil-based drilling fluids (OBDFs), an oil-absorbent polymer (OAP) composed by methylmethacrylate (MMA), butyl acrylate (BA), and hexadecyl methacrylate (HMA) was synthesized by suspension polymerization and characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and scanning electronic microscopy (SEM). The oil-absorptive capacity of OAP under different solvents was measured as the function of temperature and time. The effect of the OAP on the rheological and filtration properties of OBDFs was initially evaluated, and then the sealing property of OAP particles as lost circulation materials (LCMs) was examined by a high-temperature and high-pressure (HTHP) filtration test, a sand bed filtration test, a permeable plugging test, and a fracture sealing testing. The test results indicated that the addition of OAP had relatively little influence on the rheological properties of OBDF at content lower than 1.5 w/v % but increased the fluid viscosity remarkably at content higher than 3 w/v %. It could reduce the HTHP filtration and improve the sealing capacity of OBDF significantly. In the sealing treatment, after addition into the OBDF, the OAP particles could absorb oil accompanied with volume enlargement, which led to the increase of the fluid viscosity and slowing down of the fluid loss speed. The swelled and deformable OAP particles could be squeezed into the micro-fractures with self-adoption and seal the loss channel. More important, fluid loss was dramatically reduced when OAP particles were combined with other conventional LCMs by a synergistic effect. [ABSTRACT FROM AUTHOR]