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Abstract Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-β, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.

Abstract Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer–immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Soil properties play a crucial role in the stability of engineering foundations, particularly in cold regions where temperature gradients impact water migration and soil conditions. This study utilized MRI-Cryogenic Soil-Moisture Analyzer (MRI-CSMA) to conduct indoor freeze-thaw experiments on silty clay specimens with varying initial water contents (12.0 %, 16.8 %, and 21.1 %). Dynamic changes in water content and temperature at different soil depths were analyzed. The results revealed distinct stage decrease characteristics in both temperature and water content as freezing progressed, with more pronounced changes closer to the cold end. Conversely, during thawing, temperatures and water content gradually increased as the boundary temperature rose. Notably, after the freeze-thaw cycle, the frozen zone consistently retained higher water content than the unfrozen zone, indicating water redistribution, regardless of initial water content levels. Furthermore, in three soil samples with different initial water contents, the water migration flux in the unfrozen soil layer decreased exponentially as freezing time increased. This phenomenon can be attributed to the combined effects of water boundary conditions, temperature gradients, and soil structure changes during soil freezing. These findings are likely to have significant implications for understanding water-heat dynamics in cold region soils as well as ensuring the stability of engineering projects.

Abstract This study made triangulated use of eye-tracking and retrospective verbal reports (RVRs) to compare the banked gap-filling processes of two same-scorers and those of a top scorer and a bottom scorer. The two same-scorers differed in their cognitive effort on global and local processing, fluency of choice making, and strategy use when completing the task and half of the mutual correct responses. Contrary to findings from previous studies, the top scorer exerted much greater effort on global and local processing than the bottom scorer, in her pursuit of perfection, and she reported much less use of syntax analysis as a strategy. The findings of this study increase our understanding of individual differences in the cognitive processes of English-as-a-foreign-language (EFL) reading and test-taking and prove the value of in-depth, multi-faceted process research. Featuring the use of heatmaps, eye-tracking metrics, choice-making graphs, gaze plots, and RVRs, this study also responds to an emergent concern in language assessment about how the enormous process data can be handled effectively. Implications for testing and learning EFL reading are further developed.

Adaptive lymphocytes express a panel of immunoreceptors on the cell surface. Phospholipids are the major components of cell membranes, but they have functional roles beyond forming lipid bilayers. In particular, acidic phospholipids forming microdomains in the plasma membrane can ionically interact with proteins via polybasic sequences, which can have functional consequences for the protein. We have shown that negatively charged acidic phospholipids can interact with positively charged juxtamembrane polybasic regions of immunoreceptors, such as TCR-CD3, CD28 and IgG-BCR, to regulate protein structure and function. Furthermore, we pay our attention to protein transmembrane domains. We show that a membrane-snorkeling Lys residue in integrin αLβ2 regulates transmembrane heterodimer formation and integrin adhesion through ionic interplay with acidic phospholipids and calcium ions (Ca2+) in T cells, thus providing a new mechanism of integrin activation. Here, we review our recent progress showcasing the importance of both juxtamembrane and intramembrane ionic protein-lipid interactions. [ABSTRACT FROM AUTHOR]

Multiple digital watermarking is an important and challenging task in geographic information science and data security. Vector geographic data are a basic data format for digital geographic data storage, and the security protection of these data involves copyright protection and tracking. As part of the solution, existing digital watermarking algorithms have made contributions to vector geographic data protection. However, when vector geographic data flow through multiple units, they need to be marked to ensure that the original data are not destroyed during data processing. Existing single or multiple data watermarking algorithms often fail in the presence of data processing because the new watermarks overlay the old ones. Consequently, a multiple digital watermarking algorithm based on multiple QIM (quantization index modulation) is proposed. First, based on traditional quantization index modulation (QIM), a multiple QIM is proposed. Unlike traditional QIM, in multiple QIM, the process of quantization is executed multiple times depending on the number of watermarks. Then, the vertices are quantized into different quantization intervals according to the multiple QIM. Finally, multiple watermarks are embedded into different quantization intervals to reduce the interference among multiple watermarks, and the original watermarks are not needed in the process of watermark detection. We then conducted experiments to test the multiple watermark method’s robustness and capacity, with an emphasis on datasets with a lower data volume. The experimental results show that the proposed algorithm achieves good performance in terms of its robustness against common issues, such as vertices addition, data simplification, data cropping, and feature deletion; this holds true for both normal and small amounts of data. Additionally, it has a high multiple watermark capacity.

Due to the existence of an electric double layer in the soil, frozen soil always has a certain amount of unfrozen water. And it will migrate under the action of the electric field. Select a kind of frost heave-sensitive soil (Lanzhou loess) as the object of study, and several bench-scale experiments on frozen Lanzhou loess were performed using 4, 6, 8, 10, and 12 V/cm potential gradients. The water content was measured after tests to investigate the relationship between water migration and applied potential gradient. The current was monitored during the experiments to calculate the energy consumption, and to evaluate the usability of electroosmosis in the frozen soil. The amount of water migration increase with the increase of potential gradient and the varied water content with potential gradients can be divided into steady, fluctuation, and incremental stage. The variation of current can reflect the process of water migration to a certain extent and can be divided into two stages, and water migration mainly occurs at the stage of drastic change of current.

Antigen-triggered T-cell receptor (TCR) phosphorylation is the first signaling event in T cells to elicit adaptive immunity against invading pathogens and tumor cells. Despite its physiological importance, the underlying mechanism of TCR phosphorylation remains elusive. Here, we report a key mechanism regulating the initiation of TCR phosphorylation. The major TCR kinase Lck shows high selectivity on the four CD3 signaling proteins of TCR. CD3e is the only CD3 chain that can efficiently interact with Lck, mainly through the ionic interactions between CD3e basic residue-rich sequence (BRS) and acidic residues in the Unique domain of Lck. We applied a TCR reconstitution system to explicitly study the initiation of TCR phosphorylation. The ionic CD3e-Lck interaction controls the phosphorylation level of the whole TCR upon antigen stimulation. CD3e BRS is sequestered in the membrane, and antigen stimulation can unlock this motif. Dynamic opening of CD3e BRS and its subsequent recruitment of Lck thus can serve as an important switch of the initiation of TCR phosphorylation. [ABSTRACT FROM AUTHOR]

Vector geographic data play an important role in location information services. Digital watermarking has been widely used in protecting vector geographic data from being easily duplicated by digital forensics. Because the production and application of vector geographic data refer to many units and departments, the demand for multiple watermarking technology is increasing. However, multiple watermarking algorithm for vector geographic data draw less attention, and there are many urgent problems to be solved. Therefore, an efficient robust multiple watermark algorithm for vector geographic data is proposed in this paper. The coordinates in vector geographic data are first randomly divided into non-repetitive sets. The multiple watermarks are then embedded into the different sets. In watermark detection correlation, the Lindeberg theory is used to build a detection model and to confirm the detection threshold. Finally, experiments are made in order to demonstrate the detection algorithm, and to test its robustness against common attacks, especially against cropping attacks. The experimental results show that the proposed algorithm is robust against the deletion of vertices, addition of vertices, compression, and cropping attacks. Moreover, the proposed detection algorithm is compatible with single watermarking detection algorithms, and it has good performance in terms of detection efficiency.

The Qinghai-Tibet Plateau (QTP) is known as the Third Polar of the earth and the Water Tower of Asia, with more than 70% of the area on the QTP is covered by permafrost possibly. An accurate permafrost distribution map based on valid and available methods is indispensable for the local environment evaluation and engineering constructions planning. Most of the previous permafrost maps have employed traditional mapping method based on field surveys and borehole investigation data. However their accuracy is limited because it is extremely difficulties in obtaining mass data in the high-altitude and cold regions as the QTP; moreover, the mapping method, which would effectively integrate many factors, is still facing great challenges. With the rapid development of remote sensing technology in permafrost mapping, spatial data derived from the satellite sensors can recognize the permafrost environment features and quantitatively estimate permafrost distribution. Until now there is no map indicated permafrost presence/absence on the QTP that has been generated only by remote sensing data as yet. Therefore, this paper used permafrost-influencing factors and examined distribution features of each factor in permafrost regions and seasonally frozen ground regions. Then, using the Decision Tree method with the environmental factors, the 1 km resolution permafrost map over the QTP was obtained. The result shows higher accuracy compared to the previous published map of permafrost on the QTP and the map of the glaciers, frozen ground and deserts in China, which also demonstrates that making comprehensive use of remote sensing technology in permafrost mapping research is fast, macro and feasible. Furthermore, this result provides a simple and valid method for further permafrost research.