Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.
Finding shortest paths is a fundamental operator in spatial databases. Recently, terrain datasets have attracted a lot of attention from both industry and academia. There are some interesting issues to be studied in terrain datasets which cannot be found in a traditional two-dimensional space. In this paper, we study one of the issues called a slope constraint which exists in terrain datasets. In this paper, we propose a problem of finding shortest paths with the slope constraint. Then, we show that this new problem is more general than the traditional problem of finding shortest paths without considering the slope constraint. Since finding shortest paths with the slope constraint is costly, we propose a new framework called surface simplification so that we can compute shortest paths with the slope constraint efficiently. Under this framework, the surface is "simplified" such that the complexity of finding shortest paths on this simplified surface is lower. We conducted experiments to show that the surface simplification is very efficient and effective not only for the new problem with the slope constraint but also the traditional problem without the slope constraint.
Large‐scale geodetic measurements of crustal deformation in the north‐central Tibetan Plateau are crucial for improved understanding of earthquake‐cycle processes and long‐term seismic hazard assessment. We use GPS velocities and Interferometric Synthetic Aperture Radar (InSAR) observations (2015–2020) on eight descending and eight ascending Sentinel‐1 tracks to map surface motions and their gradients for an area of over ∼2,000 km × 350 km around the Kunlun‐Manyi fault system. The derived line‐of‐sight (LOS) and 3D velocity fields demonstrate ongoing postseismic transients along the ruptured segments of the 1997 Manyi and 2001 Kokoxili earthquakes, interseismic deformation along locked fault segments, and strain accumulation on a large subsidiary fault (i.e., the Kunlun Pass fault). We use elastic dislocation and analytical postseismic deformation models constrained by our dense InSAR measurements to quantify the interseismic and postseismic contributions, which reveal the along‐fault distribution of fault slip rate and locking depth along the entire length of the fault. The results indicate that the slip rate of the Kunlun fault systematically decreases toward the west to the west of the Taiyang Lake fault. We also find that the interseismic strain accumulation rate along the main trace of the Kunlun fault is to first‐order spatially constant (0.1–0.15 microstrain/yr), except around its restraining bend. As the historically unruptured segments, especially the eastern segments (from 95°E to 101°E) of the Kunlun fault, have relatively fast slip rates and high locking depths (>15 km), they have the potential to generate large and damaging earthquakes in this region.
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