Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Jacobian-free Newton Krylov (JFNK) is an attractive method to solve nonlinear equations in nuclear engineering systems, and has been successfully applied to steady-state neutron diffusion (k-eigenvalue) problems and multi-physics coupling problems. Preconditioning technique plays an important role in JFNK algorithm, significantly affecting computational efficiency. The key point is how to automatically construct a high-quality preconditioning matrix that can improve the convergence rate, and perform the preconditioning matrix factorization efficiently. An efficient reordering-based ILU(k) preconditioner is proposed to achieve the above objectives. In detail, the finite difference technique combined with the coloring algorithm is utilized to construct an efficient preconditioning matrix with low computational cost automatically. Furthermore, the reordering algorithm is employed for the ILU(k) to reduce the additional non-zero elements and pursue robust computational performance. A two-dimensional LRA neutron steady-state benchmark problem is used to evaluate the performance of the proposed preconditioning technique, and steady-state neutron diffusion problem with thermal-hydraulic feedback is also utilized as a supplement. The results show that coloring algorithms can efficiently and automatically construct the preconditioning matrix. The reordering-based ILU(k) preconditioner shows excellent robustness, avoiding the effect of fill-in levels k choice in incomplete LU factorization.

Three new compounds (1, 11 and 12), together with 32 known ones, were isolated from the root bark of Morus alba L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR and HRESIMS data analysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature. All the isolates were evaluated for their cytotoxic activities against human gastric cancer HGC27 cells by CCK-8 assay. Among them, compounds 5, 8, 10 and 30 exhibited cytotoxic activities on HGC27 cells with IC50 values of 10.24 ± 0.89 μM, 28.94 ± 0.72 μM, 6.08 ± 0.34 μM and 33.76 ± 2.64 μM, respectively. Furthermore, compound 10 was confirmed to reduce proliferation ability, increase apoptosis rate and inhibit cell migration pathway by annexin V/PI double staining experiment, transwell experiment and western blot analysis.

In order to alleviate the conflict between populations and land-resource, Tianjin has adopted multi-phase reclamation projects to formed large-scale artificial reclamation land. However, the reclamation areas are susceptible to subsidence, which demonstrate a serious threat to infrastructure and people’s lives and property. The SBAS-InSAR was used to acquired surface deformation of Tianjin Binhai New Area from January 2017 year to December 2022 year, analyzed in depth the response relationship between land subsidence and reclamation projects time as well as the land use type. The results show that the Lingang Industrial Zone was the earliest to be reclaimed, with extensive reclamation completed by 2016 year, while Nangang Industrial Zone and Hangu Port started reclamation projects in 2009 year, some areas are still currently under construction. There is a strong correlation between surface deformation and reclamation time, the severe land subsidence occurred over newly reclaimed areas. Surface deformation gradually intensifies from west to east, the maximum surface settlement in Nangang Industrial Zone, Lingang Industrial Zone from the west to the east has changed from -50 mm to -890 mm,45 mm to -580 mm, respectively, reclamation area of Hangu Port with maximum surface deformation is -250 mm. Significant differences deformation among different land use types, which reclamation projects completed in the same time. Subsidence is positively correlated with surface load, in areas with higher surface loads, the surface settlement is also severer,the average surface settlement for the heavy shipyard, 67 grain storage tanks, 27 grain storage tanks, road, and bare land are -201 mm, -166 mm, -107 mm, -64 mm, and -43 mm, respectively. This study reveals significant differences of surface deformation in the reclamation completed at different times and the load is the main driving factor of settlement difference in the reclamation land completed at the same time. Which has important guiding significance for preventing and controlling geological disasters in the reclamation area and later development planning.