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Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to pyroptosis in defense against an intracellular bacterial infection. We previously engineered Salmonella enterica serovar Typhimurium to persistently express flagellin, and thereby activate NLRC4 during systemic infection in mice. The resulting pyroptosis clears this flagellin-engineered strain. We now show that infection of caspase-1 or gasdermin D deficient macrophages by this flagellin-engineered S. Typhimurium induces apoptosis in vitro. Additionally, we engineered S. Typhimurium to translocate the pro-apoptotic BH3 domain of BID, which also triggers apoptosis in macrophages in vitro. During mouse infection, the apoptotic pathway successfully cleared these engineered S. Typhimurium from the intestinal niche but failed to clear the bacteria from the myeloid niche in the spleen or lymph nodes. In contrast, the pyroptotic pathway was beneficial in defense of both niches. To clear an infection, cells may have specific tasks that they must complete before they die; different modes of cell death could initiate these ‘bucket lists’ in either convergent or divergent ways.

Caspases are a family of proteins involved in cell death. Although several caspase members have been well characterized, caspase-2 remains enigmatic. Caspase-2 has been implicated in several phenotypes, but there has been no consensus in the field about its upstream activating signals or its downstream protein targets. In addition, the unique ability of caspase-2 to form a disulfide-bonded dimer has not been studied in depth. Herein, we investigate the disulfide bond in the context of inducible dimerization, showing that disulfide bond formation is dimerization dependent. We also explore and review several stimuli published in the caspase-2 field, test ferroptosis-inducing stimuli, and study in vivo infection models. We hypothesize that the disulfide bond will ultimately prove to be essential for the evolved function of caspase-2. Proving this will require the discovery of cell death phenotypes where caspase-2 is definitively essential.

The innate immune response is the first-line host defense against pathogens. Cytosolic nucleic acids, including both DNA and RNA, represent a special type of danger signal to initiate an innate immune response. Activation of cytosolic nucleic acid sensors is tightly controlled in order to achieve the high sensitivity needed to combat infection while simultaneously preventing false activation that leads to pathologic inflammatory diseases. In this review, we focus on post-translational modifications of key cytosolic nucleic acid sensors that can reversibly or irreversibly control these sensor functions. We will describe phosphorylation, ubiquitination, SUMOylation, neddylation, acetylation, methylation, succinylation, glutamylation, amidation, palmitoylation, and oxidation modifications events (including modified residues, modifying enzymes, and modification function). Together, these post-translational regulatory modifications on key cytosolic DNA/RNA sensing pathway members reveal a complicated yet elegantly controlled multilayer regulator network to govern innate immune activation.

Nowadays, the synthesis and characterization of gold nanoparticles (AuNPs) from plant based extracts and effects of their anticancer have concerned an important interest. Marsdenia tenacissima (MT), a conventional Chinese herbal medicine, has long been used for thousands of years to treat tracheitis, asthma, rheumatism, etc. In this present study, we optimize the reaction of parameters to manage the nanoparticle size, which was categorized by high-resolution transmission electron microscopy (HR-TEM). A different characterization method, for example, UV-visible spectroscopy (UV-vis), fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were performed to consider the synthesized AuNPs getting from the MT leaf extract. The MT-AuNPs were analyzed for their cytotoxicity property against HepG2 cells by MTT analysis. The apoptosis was evaluated by using reactive oxygen species (ROS), migration assay, mitochondrial membrane potential (MMP) and apoptotic protein expression. Interestingly, the findings of our study observed the cytotoxicity effect of synthesized MT-AuNPs at a concentration of 59.62 ± 4.37 μg after 24 hrs treatment. Apoptosis was induced by the MT-AuNPs with enhanced ROS, changed MMP and inhibit the migration assay. Finally, the apoptosis was confirmed by the considerable up-regulation of Bax, caspase-9 and caspase-3, while the anti-apoptotic protein expressions of Bcl-2 and Bcl-XL were down-regulated. Although, in this studies, we evaluated the characterization, synthesis and anticancer action of gold nanoparticles from MT (MT-AuNPS) helpful for liver cancer therapeutics.

Herpes simplex virus type 1 (HSV-1) infection can manifest locally as mucocutaneous lesions or keratitis and can also spread to the central nervous system to cause encephalitis. HSV-1 establishes a lifelong latent infection and neither cure nor vaccine is currently available. The innate immune response is the first line of defense against infection. Caspases and gasdermins are important components of innate immunity. Caspases are a family of cysteine proteases, most of which mediate regulated cell death. Gasdermins are a family of pore-forming proteins that trigger lytic cell death. To determine whether caspases or gasdermins contribute to innate immune defenses against HSV-1, we screened mice deficient in specific cell death genes. Our results indicate a modest role for caspase-6 in defense against HSV-1. Further, Asc–/–Casp1/11–/– mice also had a modest increased susceptibility to HSV-1 infection. Caspase-7, -8, and -14 did not have a notable role in controlling HSV-1 infection. We generated Gsdma1-Gsdma2-Gsdma3 triple knockout mice, which also had normal susceptibility to HSV-1. We confirmed that the previously published importance of RIPK3 during systemic HSV-1 infection also holds true during skin infection. Overall, our data highlight that as a successful pathogen, HSV-1 has multiple ways to evade host innate immune responses.

This study offers a new approach for studying biblical myth in two directions: first, by expanding the scope of investigation beyond the clearly mythological elements to other areas of biblical literature, and second, by drawing comparisons to classical Chinese literature. This article thus reconsiders the relationship between myth and history in both biblical and Chinese literature, while seeking to broaden the endeavor of the comparative method in biblical studies. Two examples are offered: (1) the story of Moses’s call narrative and his relationship with Aaron in Exodus in light of the story of Xiang Liang and Xiang Ji in the Shiji; (2) the story of Saul and David in 1 Samuel compared with the story of Dong Zhuo and Lü Bu in the Romance of the Three Kingdoms. Both comparisons demonstrate the operation of Claude Lévi-Strauss’s inversion principle. Conclusions regarding each of these literatures are presented separately, followed by cross-cultural insights and shared aspects in the study of myth, historiography, and religion.

Abstract This study aimed to investigate whether class A1 scavenger receptor (SR-A1) regulated macrophage polarization and gut microbial alteration during intestinal inflammation of colitis. A murine colitis model was established by feeding with dextran sulfate sodium (DSS), and treatment groups were injected intravenously with SR-A1 antibody. Results showed a preventive effect on colitis symptoms and fewer inflammatory cell infiltrates in treatment groups. Down-regulation of inflammatory cytokines and up-regulation of anti-inflammatory cytokine related to macrophages were seen in murine PBMC and LPMC after injected with SR-A1 antibody. The percentage of M2 macrophages was also elevated in treatment groups. In addition, SR-A1 antibody treatment resulted in the decreased apoptosis and increased proliferation of colonic epithelial cells. Other findings indicated that SR-A1 antibody injection could mediate its anti-inflammatory effect via inhibiting TLR4-MyD88-NF-kB signaling pathway and alterating the gut microbiota composition. Our research identified SR-A1 as a potential therapeutic target in inflammatory bowel disease (IBD).

The article focuses on the relationship between beauty and intellect in ancient Chinese and Jewish texts, particularly in Confucian and rabbinic traditions. The article seeks to compare and explore shared themes in these civilizations and highlight their resistance to singular interpretations or consistent outlooks on beauty and intellect.

Reconstructing 3D structures from non-overlapping multi-view images is a crucial task in the field of 3D computer vision, since it is difficult to establish feature correspondences and infer depth from overlapping parts of views. Previous methods, whether generating the surface mesh or volume of an object, face challenges in simultaneously ensuring the accuracy of detailed topology and the integrity of the overall structure. In this paper, we introduce a novel coarse-to-fine Transformer-based reconstruction network to generate precise point clouds from multiple input images at sparse and non-overlapping viewpoints. Specifically, we firstly employ a general point cloud generation architecture enhanced by the concept of adaptive centroid constraint for the coarse point cloud corresponding to the object. Subsequently, a Transformer-based refinement module applies deformation to each point. We design an attention-based encoder to encode both image projection features and point cloud geometric features, along with a decoder to calculate deformation residuals. Experiments on ShapeNet demonstrate that our proposed method outperforms other competing methods.

Abstract Background Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 was reported to inhibit the proliferation and metastasis of papillary thyroid cancer cells, but its role in PCa has not been reported. This study aims to investigate the role and underlying mechanism of LINC00893 in regulating the progression of PCa cells. Methods We first compared LINC00893 expression levels between PCa tissues and normal prostate tissues through TCGA database. The relative LINC00893 expression levels were further validated in 66 pairs of PCa tissues and para-cancerous normal tissues, as well as in PCa cell lines. Gain-of-function experiment was performed by transfecting PCa cell with LINC00893 expression vector, and CCK (Cell count kit)-8, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation, colony information and transwell assays were conducted to assess the functional phenotypes. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays were performed to evaluate the molecular interactions. Results LINC00893 was downregulated in PCa tissues and cell lines, and patients with low expression of LINC00893 were associated with a poorer overall survival rate. LINC00893 overexpression hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as the migratory ability of PCa cells, and suppressed the tumorigenesis of PCa cells in nude mice. We further demonstrated that LINC00893 acted as a sponge for miR-3173-5p and inhibited its activity, which in turn regulated the suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis. Conclusions Our study demonstrated that LINC00893 suppresses the progression of PCa cells through targeting miR-3173-5p/SOCS3/JAK2/STAT3 axis. Our data uncovers a novel tumor-suppressor role of LINC00893 in PCa, which may serve as a potential strategy for targeted therapy in PCa. Grapical Abstract

Abstract This study aimed to investigate whether serum indicators related to iron stores in the body are associated with clinical and endoscopic disease severity. Eighty-four patients with Crohn’s disease (CD) and twenty-four healthy volunteers were included. The indicators related to iron stores were detected within one week after endoscopic and CT enterography examinations. Patients were divided into three groups according to the CDAI(Crohn's disease activity index)scores. Serum iron levels were decreased in all groups (p 0.05). Underweight, decreased serum iron and TIBC were independent risk factors for moderate clinical disease. Combined detection of decreased serum iron and TIBC was helpful in differentiating severe patients. The sensitivity and specificity were 32.7% and 100%, respectively (AUC = 0.812, p

Background: Grading of endoscopic lesions is important for determining the severity of ulcerative colitis and developing treatment strategies, but the commonly used methods are not sufficient. Objectives: This study aimed to investigate whether new endoscopic scoring systems incorporating lesions and disease extent are associated with clinical disease severity and maintainable remission. Design: This was a retrospective study. In all, 110 patients with ulcerative colitis were included and 87 completed 12-month follow-up. Methods: Colonoscopy was performed within 1 week before blood samples were taken. Degree of ulcerative colitis burden of luminal inflammation (DUBLIN) scores were calculated as the product of Mayo endoscopic score (MES) by disease extent and ulcerative colitis endoscopic index of severity was used to replace MES when calculating modified DUBLIN scores. Results: DUBLIN and modified DUBLIN scores were increased in the moderate and severe groups significantly ( p 7) were associated with an increased risk of treatment failure (hazard ratio = 4.96, 95% confidence interval: 1.17–21.00, p = 0.03), but there were no association between DUBLIN scores and long-term remission ( p > 0.05). Conclusion: Increased DUBLIN and modified DUBLIN scores were conducive to screening serious disease, but only modified DUBLIN scores had the potential to assist in making an upgraded therapeutic schedule.

The surface mesh reconstruction from point clouds has been a fundamental research topic in Computer Vision and Computer Graphics. Recently, the Neural Implicit Representation (NIR)-based reconstruction has revolutionized this research topic. This work summarizes and analyzes representative works on NIR-based reconstruction and highlights several important insights. However, one major problem with existing works is that they struggle to handle high-resolution meshes. To address this, this paper introduces HRE-NDC, a novel High-Resolution and Efficient Neural Dual Contouring approach for mesh reconstruction from point clouds, which takes the previous state-of-the-art as a baseline and adopts a coarse-to-fine network structure design, along with feature-preserving downsampling and other improvements. HRE-NDC significantly reduces training time and memory usage while achieving better surface reconstruction results. Experimental results demonstrate the superiority of our method in both visualization and quantitative results, and it shows excellent generalization performance on various data including large indoor scenes, real-scanned urban buildings, clothing, and human bodies.

Background The molecular mechanisms responsible for angiogenesis and abnormal expression of angiogenic factors in gastric cancer, including vascular endothelial growth factor (VEGF), remain unclear. The histone demethylase retinoblastoma binding protein 2 (RBP2) is involved in gastric tumorgenesis by inhibiting the expression of cyclin-dependent kinase inhibitors (CDKIs). Methods The expression of RBP2, VEGF, CD31, CD34 and Ki67 was assessed in 30 human gastric cancer samples and normal control samples. We used quantitative RT-PCR, western blot analysis, ELISA, tube-formation assay and colony-formation assay to characterize the change in VEGF expression and associated biological activities induced by RBP2 silencing or overexpression. Luciferase assay and ChIP were used to explore the direct regulation of RBP2 on the promoter activity of VEGF. Nude mice and RBP2-targeted mutant mice were used to detect the role of RBP2 in VEGF expression and angiogenesis in vivo. Results RBP2 and VEGF were both overexpressed in human gastric cancer tissue, with greater microvessel density (MVD) and cell proliferation as compared with normal tissue. In gastric epithelial cell lines, RBP2 overexpression significantly promoted the expression of VEGF and the growth and angiogenesis of the cells, while RBP2 knockdown had the reverse effect. RBP2 directly bound to the promoter of VEGF to regulate its expression by histone H3K4 demethylation. The subcutis of nude mice transfected with BGC-823 cells with RBP2 knockdown showed reduced VEGF expression and MVD, with reduced carcinogenesis and cell proliferation. In addition, the gastric epithelia of RBP2 mutant mice with increased H3K4 trimethylation showed reduced VEGF expression and MVD. Conclusions The promotion of gastric tumorigenesis by RBP2 was significantly associated with transactivation of VEGF expression and elevated angiogenesis. Overexpression of RBP2 and activation of VEGF might play important roles in human gastric cancer development and progression. [ABSTRACT FROM AUTHOR]

Impact craters refer to the most salient features on the moon surface. They are of huge significance for analyzing the moon topography, selecting the lunar landing site and other lunar exploration missions, etc. However, existing methods of impact crater detection have been largely implemented on the optical image data, thereby causing them to be sensitive to the sunlight. Thus, these methods can easily achieve unsatisfactory detection results. In this study, an original two-stage small crater detection method is proposed, which is sufficiently effective in addressing the sunlight effects. At the first stage of the proposed method, a semantic segmentation is conducted to detect small impact craters by fully exploiting the elevation information in the digital elevation map (DEM) data. Subsequently, at the second stage, the detection accuracy is improved under the special post-processing. As opposed to other methods based on DEM images, the proposed method, respectively, increases the new crusher percentage, recall and crusher level F1 by 4.89%, 5.42% and 0.67%.

Point cloud registration is one of the basic research hotspots in the field of 3D reconstruction. Although many previous studies have made great progress, the registration of rock point clouds remains an ongoing challenge, due to the complex surface, arbitrary shape, and high resolution of rock masses. To overcome these challenges, a novel registration method for rock point clouds, based on local invariants, is proposed in this paper. First, to handle the massive point clouds, a point of interest filtering method based on a sum vector is adopted to reduce the number of points. Second, the remaining points of interest are divided into several cluster point sets and the centroid of each cluster is calculated. Then, we determine the correspondence between the original point cloud and the target point cloud by proving the inherent similarity (using the trace of the covariance matrix) of the remaining point sets. Finally, the rotation matrix and translation vector are calculated, according to the corresponding centroids, and a correction method is used to adjust the positions of the centroids. To illustrate the superiority of our method, in terms of accuracy and efficiency, we conducted experiments on multiple datasets. The experimental results show that the method has higher accuracy (about ten times) and efficiency than similar existing methods.

China’s Chang’e lunar exploration project obtains digital orthophoto image (DOM) and digital elevation model (DEM) data covering the whole Moon, which are critical to lunar research. The DOM data have three resolutions (i.e., 7, 20 and 50 m), while the DEM has two resolutions (i.e., 20 and 50 m). Analysis and research on these image data effectively help humans to understand the Moon. In addition, impact craters are considered the most basic feature of the Moon’s surface. Statistics regarding the size and distribution of impact craters are essential for lunar geology. In existing works, however, the lunar surface has been reconstructed less accurately, and there is insufficient semantic information regarding the craters. In order to build a three-dimensional (3D) model of the Moon with crater information using Chang‘e data in the Chang‘e reference frame, we propose a four-step framework. First, software is implemented to annotate the lunar impact craters from Chang’e data by complying with our existing study on an auxiliary annotation method and open-source software LabelMe. Second, auxiliary annotation software is adopted to annotate six segments in the Chang’e data for an overall 25,250 impact crater targets. The existing but inaccurate craters are combined with our labeled data to generate a larger dataset of craters. This data set is analyzed and compared with the common detection data. Third, deep learning detection methods are employed to detect impact craters. To address the problem attributed to the resolution of Chang’e data being too high, a quadtree decomposition is conducted. Lastly, a geographic information system is used to map the DEM data to 3D space and annotate the semantic information of the impact craters. In brief, a 3D model of the Moon with crater information is implemented based on Chang’e data in the Chang‘e reference frame, which is of high significance.

Background The development of excellent general practitioners is essential to preserving people's health. Unfortunately, the general practitioner training model in place today is insufficient, which leaves them unqualified to provide primary medical services. Consequently, enhancing clinical competency should be the main goal of general practitioners' training. Objective To investigate how general practitioners' clinical practice abilities are affected by MDT-based CBL education. Methods From July 2020 to July 2023, 26 trainee general practitioners received training at the department of pulmonary and critical care medicine as part of their residency programme. As research subjects, they were divided three groups and trained with different model: traditional model, CBL model and MDT-based CBL model, respectively. Leicester Assessment Package (LAP) was used to assess their clinical practice skills by the end. Self-designed questionnaire was used for satisfaction survey anonymously. The results were analyzed statistically. Results The MDT-based CBL teaching group outperformed the traditional teaching group and the CBL teaching group in the theoretical examination (P

In the fields of 3D modeling, analysis of discontinuities and engineering calculation, surface extraction is of great importance. The rapid development of photogrammetry and Light Detection and Ranging (LiDAR) technology facilitates the study of surface extraction. Automatic extraction of rock surfaces from 3D rock-mass point clouds also becomes the basis of 3D modeling and engineering calculation of rock mass. This paper presents an automated and effective method for extracting rock surfaces from unorganized rock-mass point clouds. This method consists of three stages: (i) clustering based on voxels; (ii) estimating major orientations based on Gaussian Kernel and (iii) rock surface extraction. Firstly, the two-level spatial grid is used for fast voxelization and segmenting the point cloud into three types of voxels, including coplanar, non-coplanar and sparse voxels. Secondly, the coplanar voxels, rather than the scattered points, are employed to estimate major orientations by using a bivariate Gaussian Kernel. Finally, the seed voxels are selected on the basis of major orientations and the region growing method based on voxels is applied to extract rock surfaces, resulting in sets of surface clusters. The sub-surfaces of each cluster are coplanar or parallel. In this paper, artificial icosahedron point cloud and natural rock-mass point clouds are used for testing the proposed method, respectively. The experimental results show that, the proposed method can effectively and accurately extract rock surfaces in unorganized rock-mass point clouds.

Histogram statistics has important applications in the fields of image enhancement and target detection. However, with the increasing size of the image and the higher real-time requirements, the processing process of the histogram statistical local enhancement algorithm is slow and cannot reach the expected satisfactory speed. In view of this deficiency, this paper realizes the parallel processing of histogram statistical image enhancement algorithm on graphics processing unit (GPU) platform, which improves the processing speed of large format digital images. Firstly, the efficiency of data access is improved by making full use of compute unified device architecture (CUDA) active thread block and active thread to process different sub-image blocks and pixels in parallel. Then, the paralle-lization of histogram statistical image enhancement algorithm on GPU platform is realized by using kernel configu-ration parameter optimization and data parallel computing technology. Finally, the efficient data transmission mode between the host and the device is adopted, which further shortens the execution time of the system on the hetero-geneous computing platform. The results show that for images with different image sizes, the processing speed of the image histogram statistical parallel algorithm is two orders of magnitude higher than that of the CPU serial algorithm. It takes 787.11 ms to process an image with an image size of 3241×3685. The processing speed of the parallel algo-rithm is increased by 261.35 times. It lays a good foundation for the realization of real-time large-scale image processing.