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Diabetic kidney dysfunction is closely associated with renal fibrosis. Although the suppression of fibrosis is crucial to attenuate kidney damage, the underlying mechanisms remain poorly understood. In this study, renal injury in diabetic mice was induced by the intraperitoneal injection of streptozotocin (100 or 150 mg/kg) for 2 consecutive days. In the model mice, remarkable renal injury was observed, manifested by albuminuria, swelling of kidneys, and histopathological characteristics. The renal fibrosis was obviously displayed with high-intensity staining of fibrin, type IV collagen (Col IV), and fibronectin. The levels of Col IV and transforming growth factor-β1 were significantly increased in diabetic mice kidneys. The aggravated fibrotic process was associated with the overexpression of HMGB1, TLR2/4, and p-NF-κB. Furthermore, a high expression of F4/80 and CD14 indicated that macrophage infiltration was involved in perpetuating inflammation and subsequent fibrosis in the kidneys of diabetic mice. The results demonstrate that the severity of renal fibrosis is positively associated with the activation of HMGB1/TLR2/4 signaling in diabetes.

Improving the resolution of seismic migration images plays an important role for geophysical interpreters to characterize underground reservoirs. However, the classical image domain least‐squares migration method based on the local‐stationary assumption cannot obtain a satisfactory high‐resolution seismic image due to the significant spatial variant characteristics of the point spread function. To mitigate this problem, we proposed a high‐resolution point spread function deconvolution method and applied it to two‐dimensional cases. Nevertheless, extending the two‐dimensional method to three‐dimensional problems directly would fail due to the intrinsic complexity in three‐dimensional cases. In this study, we resolve the differences encountered in the point spread function deconvolution method for two‐ and three‐dimensional cases and provide specific strategies for achieving high‐resolution imaging with low computational cost when extending the point spread function deconvolution method to three‐dimensional cases. The main schemes include (1) incorporating the analytical expression of the point spread function to guide the generation of three‐dimensional point spread function distributions, (2) extending the point spread function filter calculation method from a two‐dimensional square to a three‐dimensional rectangular prism and (3) interpolating to obtain more compact point spread functions for reducing migration artefacts. Results from the three‐dimensional synthetic Overthrust model and field data set demonstrate that our techniques could effectively enhance the spatial resolution of the migration images with reduced migration artefacts. With these specific strategies, the space‐variant point spread function deconvolution algorithm shows superior performance on three‐dimensional cases at a much lower computational cost compared with the classical least‐squares migration method and the local‐stationary deblurring method. Synthetic tests and real data applications confirm that the space‐variant point spread function deconvolution method has distinct advantages over both two‐ and three‐dimensional problems and can be widely adopted in practice. [ABSTRACT FROM AUTHOR]

Chromatin remodelers are commonly altered in human cancer. The mutation of AT‐rich interactive domain 1A (ARID1A) in gastric cancer (GC), a component of the SWI/SNF chromatin remodeling complex, was proven associated with treatment response in our previous study. However, ARID1A loss of function was caused not only by mutations but also copy number deletions. The clinicopathologic, genomic, and immunophenotypic correlates of ARID1A loss is largely uncharacterized in GC. Here, 819 patients with clinicopathological information and sequencing data or formalin‐fixed paraffin‐embedded tissues from four cohorts, Zhongshan Hospital (ZSHS) cohort (n = 375), The Cancer Genome Atlas (TCGA) cohort (n = 371), Samsung Medical Center (SMC) cohort (n = 53), and ZSHS immunotherapy cohort (n = 20), were enrolled. ARID1A loss was defined by genome sequencing or deficient ARID1A expression by immunohistochemistry. We found that ARID1A mutation and copy number deletion were enriched in GC with microsatellite instability (MSI) and chromosomal‐instability (CIN), respectively. In the TCGA and ZSHS cohorts, only CIN GC with ARID1A loss could benefit from fluorouracil‐based adjuvant chemotherapy. In the SMC and ZSHS immunotherapy cohorts, ARID1A loss exhibited a tendency of superior responsiveness and indicated favorable overall survival after anti‐PD‐1 immunotherapy. ARID1A‐loss tumors demonstrated elevated mutation burden, neoantigen load, and interferon gamma pathway activation. Moreover, in CIN GC, ARID1A loss was correlated with higher homologous recombination deficiency. ARID1A loss defines a distinct subtype of GC characterized by high levels of genome instability, neoantigen formation, and immune activation. These tumors show sensitivity to both chemotherapy and anti‐PD‐1 immunotherapy. This study provides valuable insights for precision treatment strategies in GC. [ABSTRACT FROM AUTHOR]