Meso/Micro-texture analysis of the landslide-dam outburst sediments in the Upper Jinsha River, SE Tibetan Plateau

Outburst sediments are widely distributed in the Upper Jinsha River in the Southeastern (SE) Tibetan Plateau. In order to understand the sedimentary characteristics of these sediments, gravel fabric, particle size distribution and quartz sand surface textures were used to analyze the mesotextures and microtextures of the Xuelongnang outburst sediments. It was determined that these sediments usually have a short transport distance, and are distributed over a distance of approximately 3.5 km. The gravel fabric and particle size distribution analysis represent the different mesotextures with different transport distances and suggest gradually changing hydrodynamic conditions. The statistical data of quartz surface textures exhibit the transformation process of quartz sands by outburst flood. The variation from abundant sub-angular shapes (> 75%); to common V-shaped percussion cracks, solution crevasse, medium relief, and chatter marks (50% to 75%); to rare meandering ridge, underwater polished surface, large conchoidal fracture (> 100 μm), directional etch pits, and crystalline overgrowths (< 5%), present the features in different combinations to other sedimentary environments. The microtexture characteristics of landslide-dam outburst deposits are also consistent with those of the mesotextures. As the distance from the residual dam increased, the quartz grain microtextures showed gradual or abrupt changes, such as increased frequencies of V-shaped percussion cracks, decreased frequencies of the adhering particles, and growth of the solution crevasses. These findings could potentially be used as a discriminant mark to distinguish outburst sediment from other types of sediments, e.g., subaqueous, eolian, glacial, etc.</p

PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes

FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

The research of pipeline lifting model in horizontal directional drilling

In recent years, Horizontal Directional Drilling has been the first choice in trenchless engineering of pipeline crossing for its strong environmental adaptability, high efficiency and low cost. In order to reduce the resistance force and avoid pipeline damage in construction, the angle formed by the pipeline axis and hole axis should be lessened when the pipeline is lifted to a height. However, the stress status of the pipeline is very complex during the lifting process. Hence the research of pipeline lifting process is great importance for pipeline safety. In this paper, a finite element model is established to uncover the stress variety law of pipeline during lifting process. And then its reliability was verified by the experimental method. At last, the results of engineering experiment show that the finite element model which is credible can be used to reveal the stress variety law of the pipeline during the lifting process

Data Supporting the Roles of BAP1, Sting, and IFN-β in ISGF3 Activation in ccRCC

The data presented in this article are companion materials to our manuscript titled BAP1 maintains HIF-dependent interferon beta induction to suppress tumor growth in clear cell renal cell carcinoma (Langbein et al., 2022), where we investigated the downstream effects of BAP1 (BRCA1-associated protein 1) expression in clear cell renal cell carcinoma (ccRCC) cell lines and mouse xenograft models. In the manuscript, we showed that BAP1 upregulates STING (stimulator of interferon genes) expression and activity in ccRCC cells, leading to IFN-β transcription and activation of interferon stimulated gene factor 3 (ISGF3), the transcription factor that mediates the effects of type I interferons (IFNs). Here, we suppressed additional components of the type I IFN pathway, including IRF9 (a component of ISGF3), IFNAR1 (the type I IFN receptor), and STING (a stimulator of IFN production) by shRNA to investigate their involvement in BAP1-mediated upregulation of ISGF3 activity. We also inhibited extracellular IFN-β via neutralizing antibody treatment in BAP1-expressing cells to ascertain the role of the secreted cytokine in this pathway. ISGF3 activity was assessed by western blot analysis and qPCR measurement of its transcriptional targets. To examine the relevance of our observations in another model system, we characterized primary kidney cells from WT and Bap1 fl/fl mice by cytokeratin 8 immunohistochemistry and examined the effect of Bap1 knockout on Sting protein expression. Finally, we treated mice bearing BAP1 knockdown xenografted tumors with diABZI, a STING agonist, and measured immune cell recruitment via CD45 immunohistochemistry. These data can serve as a starting point for further investigation on the roles of BAP1 and other tumor suppressor genes in interferon pathway regulation