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NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis. [ABSTRACT FROM AUTHOR]

The etiology of internal fruit rot of greenhouse-grown sweet pepper, caused by the fungus Fusarium lactis, was investigated during anthesis and fruit development using stereo, fluorescence and scanning electron microscopy. Proliferation of fungal mycelium was observed on the surface of the stigma one day after inoculation (DAI). Mycelial growth was also visible in the transmitting tissues of the style and inside the ovary at 5 and 6 DAI. When externally symptomless sweet pepper fruits were sectioned 45 DAI, typical internal fruit rot symptoms were observed. Culturing of hyphal-like strands and ovules from inoculated flowers on potato dextrose agar (PDA) confirmed the presence of F. lactis. Similarly, symptomless seeds from infected fruit also yielded colonies of the fungus on PDA. These findings support the hypothesis that internal fruit rot of greenhouse sweet pepper caused by F. lactis is initiated through the infection of the stigma and style during anthesis. Moreover, symptomless seed infection may contribute to disease spread between greenhouses, although further work is needed to understand how F. lactis becomes established and spreads from infected seeds to flowers. [ABSTRACT FROM AUTHOR]

NOD‐like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3‐overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders. Synopsis: The innate immune sensor NLRC3 negatively regulates dendritic cell activation to affect Th1 and Th17 cell differentiation and experimental autoimmune encephalomyelitis. NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets.Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced EAE development.NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway. [ABSTRACT FROM AUTHOR]

Composite visualization represents a widely embraced design that combines multiple visual representations to create an integrated view. However, the traditional approach of creating composite visualizations in immersive environments typically occurs asynchronously outside of the immersive space and is carried out by experienced experts. In this work, we aim to empower users to participate in the creation of composite visualization within immersive environments through embodied interactions. This could provide a flexible and fluid experience with immersive visualization and has the potential to facilitate understanding of the relationship between visualization views. We begin with developing a design space of embodied interactions to create various types of composite visualizations with the consideration of data relationships. Drawing inspiration from people's natural experience of manipulating physical objects, we design interactions based on the combination of 3D manipulations in immersive environments. Building upon the design space, we present a series of case studies showcasing the interaction to create different kinds of composite visualizations in virtual reality. Subsequently, we conduct a user study to evaluate the usability of the derived interaction techniques and user experience of creating composite visualizations through embodied interactions. We find that empowering users to participate in composite visualizations through embodied interactions enables them to flexibly leverage different visualization views for understanding and communicating the relationships between different views, which underscores the potential of several future application scenarios.

Labels are widely used in augmented reality (AR) to display digital information. Ensuring the readability of AR labels requires placing them in an occlusion-free manner while keeping visual links legible, especially when multiple labels exist in the scene. Although existing optimization-based methods, such as force-based methods, are effective in managing AR labels in static scenarios, they often struggle in dynamic scenarios with constantly moving objects. This is due to their focus on generating layouts optimal for the current moment, neglecting future moments and leading to sub-optimal or unstable layouts over time. In this work, we present RL-LABEL, a deep reinforcement learning-based method intended for managing the placement of AR labels in scenarios involving moving objects. RL-LABEL considers both the current and predicted future states of objects and labels, such as positions and velocities, as well as the user's viewpoint, to make informed decisions about label placement. It balances the trade-offs between immediate and long-term objectives. We tested RL-LABEL in simulated AR scenarios on two real-world datasets, showing that it effectively learns the decision-making process for long-term optimization, outperforming two baselines (i.e., no view management and a force-based method) by minimizing label occlusions, line intersections, and label movement distance. Additionally, a user study involving 18 participants indicates that, within our simulated environment, RL-LABEL excels over the baselines in aiding users to identify, compare, and summarize data on labels in dynamic scenes.

Automated pavement crack image segmentation presents a significant challenge due to the difficulty in detecting slender cracks on complex pavement backgrounds, as well as the significant impact of lighting conditions. In this paper, we propose a novel approach for automated pavement crack detection using a multi-scale feature fusion network based on the Transformer architecture, leveraging an encoding-decoding structure. In the encoding phase, the Transformer is leveraged as a substitute for the convolution operation, which utilizes global modeling to enhance feature extraction capabilities and address long-distance dependence. Then, dilated convolution is employed to increase the receptive field of the feature map while maintaining resolution, thereby further improving context information acquisition. In the decoding phase, the linear layer is employed to adjust the length of feature sequence output by different encoder block, and the multi-scale feature map is obtained after dimension conversion. Detailed information of cracks can be restored by fusing multi-scale features, thereby improving the accuracy of crack detection. Our proposed method achieves an F1 score of 70.84% on the Crack500 dataset and 84.50% on the DeepCrack dataset, which are improvements of 1.42% and 2.07% over the state-of-the-art method, respectively. The experimental results show that the proposed method has higher detection accuracy, better generalization and better crack detection results can be obtained under both high and low brightness conditions.

Innate immune signaling in macrophages during viral infection is regulated by ISGylation, the covalent attachment of the ubiquitin-like protein interferon-stimulated gene 15 (ISG15) to protein targets. Here, we explored the role of ISGylation in the macrophage response to infection with Mycobacterium tuberculosis . In human and mouse macrophages, the E3 ubiquitin ligases HERC5 and mHERC6, respectively, mediated the ISGylation of the phosphatase PTEN, which promoted its degradation. The decreased abundance of PTEN led to an increase in the activity of the PI3K-AKT signaling pathway, which stimulated the synthesis of proinflammatory cytokines. Bacterial growth was increased in culture and in vivo when human or mouse macrophages were deficient in the major E3 ISG15 ligase. The findings expand the role of ISGylation in macrophages to antibacterial immunity and suggest that HERC5 signaling may be a candidate target for adjunct host-directed therapy in patients with tuberculosis.

Background: 5-Methylcytosine (m5C) methylation is a major epigenetic RNA modification and is closely related to tumorigenesis in various cancers. This study aimed to explore the prognostic value of m5C-related lncRNAs in breast cancer., Methods: Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. First, we performed differentially expressed gene (DEG) analysis and constructed a PPI network for the 12 m5C regulators. Then, we identified the m5C-related LncRNAs by the "cor. test." An m5C-related lncRNA prognostic risk signature was developed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was determined using Kaplan-Meier (KM) survival analysis and ROC curves. Finally, a nomogram was constructed for clinical application in evaluating patients with BRCA. We also researched the drug sensitivity of signature lncRNAs and immune cell infiltration. Finally, we validated the expression of the signature lncRNAs through qRT-PCR in a breast cancer cell line and a breast epithelial cell line., Results: Overall, we constructed an 11-lncRNA risk score signature based on the lncRNAs associated with m5C regulators. According to the median risk score, we divided BRCA patients into high- and low-risk groups. The prognostic risk signature displayed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of immune cell subtypes. Drug sensitivity proved that our prognostic risk signature potentially has therapeutic value., Conclusions: The m5C-related lncRNA signature reliably predicted the prognosis of breast cancer patients and may provide new insight into the breast cancer tumor immune microenvironment., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Augmented Reality (AR) embeds digital information into objects of the physical world. Data can be shown in-situ, thereby enabling real-time visual comparisons and object search in real-life user tasks, such as comparing products and looking up scores in a sports game. While there have been studies on designing AR interfaces for situated information retrieval, there has only been limited research on AR object labeling for visual search tasks in the spatial environment. In this article, we identify and categorize different design aspects in AR label design and report on a formal user study on labels for out-of-view objects to support visual search tasks in AR. We design three visualization techniques for out-of-view object labeling in AR, which respectively encode the relative physical position (height-encoded), the rotational direction (angle-encoded), and the label values (value-encoded) of the objects. We further implement two traditional in-view object labeling techniques, where labels are placed either next to the respective objects (situated) or at the edge of the AR FoV (boundary). We evaluate these five different label conditions in three visual search tasks for static objects. Our study shows that out-of-view object labels are beneficial when searching for objects outside the FoV, spatial orientation, and when comparing multiple spatially sparse objects. Angle-encoded labels with directional cues of the surrounding objects have the overall best performance with the highest user satisfaction. We discuss the implications of our findings for future immersive AR interface design.

Most sports visualizations rely on a combination of spatial, highly temporal, and user-centric data, making sports a challenging target for visualization. Emerging technologies, such as augmented and mixed reality (AR/XR), have brought exciting opportunities along with new challenges for sports visualization. We share our experience working with sports domain experts and present lessons learned from conducting visualization research in SportsXR. In our previous work, we have targeted different types of users in sports, including athletes, game analysts, and fans. Each user group has unique design constraints and requirements, such as obtaining real-time visual feedback in training, automating the low-level video analysis workflow, or personalizing embedded visualizations for live game data analysis. In this article, we synthesize our best practices and pitfalls we identified while working on SportsXR. We highlight lessons learned in working with sports domain experts in designing and evaluating sports visualizations and in working with emerging AR/XR technologies. We envision that sports visualization research will benefit the larger visualization community through its unique challenges and opportunities for immersive and situated analytics.

Purpose: The prognostication for the injured recurrent laryngeal nerve (RLN) with incomplete loss of signal (LOS) and its function outcome have not been well unified. A warning criterion was proposed to predict RLN injury during monitored thyroidectomy., Methods: A retrospective review of prospectively collected data from consecutive 357 patients with 560 nerves at risk was conducted. Vocal cords mobility with laryngoscope was performed preoperatively, on the second day, and once a month postoperatively until complete recovery. Different cutoff values of the percentage reduction in sum of the amplitude of left and right channel at the end of the surgery, for postoperative vocal cord paralysis (VCP) prediction were compared., Results: Percentage reduction in sum of the amplitude of left and right channel at the end of operation ranged from 30.2 to 63.6% in 27 nerves with incomplete LOS (absolute amplitude value of final R 2  > 100 μV with reduction > 50% of R 1 ). Seven (1.25%) nerves experienced transient postoperative VCP, in which one nerve with postoperative VCP showed no amplitude reduction. The positive predictive value of VCP for the sum amplitude reduction exceeding 30, 40, 50, and 60% was 22.2, 40, 85.7, and 100%, respectively. Accuracy was 96.1, 98.2, 99.6, 99.4%, respectively., Conclusion: Percentage reduction in sum of the amplitude of left and right channel is a meaningful method to improve the accuracy of VCP prediction. When the sum amplitude reduction ≥ 50%, surgeons should consider the possibility of postoperative VCP and correct some surgical maneuvers., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Macrophage is the important sentinel cell type of innate immune system, and bridge with the adaptive immune response via antigen presentation. Tissue-resident macrophages are universal in almost all organs and play essential roles in maintaining specific organ homeostasis, inflammation responses, and disease genesis, including tumorigenesis. Macrophage is generally divided into two extreme statuses, M1 and M2, with sophisticated continuous subtypes due to different stimuli and microenvironments. Tumor-associated macrophage (TAM) is regarded as the key factor related to the prognosis, staging, classification, and treatment strategy of various cancers. However, emerging evidence indicated potential opposite functions of TAM in different tumor models. Recent studies found that different originated resident macrophages show notably different profiles in the same tissue niche. More evidence pointed out that the strategies to repolarize the subtypes of TAM or resident macrophages are valuable in carcinoma treatments. In the breast cancer model, studies pointed that macrophages located differently in histology show obvious different cell markers and functions. In this review, we will illustrate the profiles of resident macrophages in breast cancer with various aspects, including origination, polarization, tumoricidal activity, tumorigenesis, and the factors that could regulate the functions of macrophages., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4 + T cell activation. USP12 plays an intrinsic role in promoting the CD4 + T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4 + T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4 + T cells, but not in CD8 + T cells. Our study results showed that USP12 activated CD4 + T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64 hi MHCII lo and CD64 lo MHCII hi macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs., Competing Interests: The authors declare no competing interest.

NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4 + T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders., (© 2019 The Authors.)

Immersive virtual- and augmented-reality headsets can overlay a flat image against any surface or hang virtual objects in the space around the user. The technology is rapidly improving and may, in the long term, replace traditional flat panel displays in many situations. When displays are no longer intrinsically flat, how should we use the space around the user for abstract data visualisation? In this paper, we ask this question with respect to origin-destination flow data in a global geographic context. We report on the findings of three studies exploring different spatial encodings for flow maps. The first experiment focuses on different 2D and 3D encodings for flows on flat maps. We find that participants are significantly more accurate with raised flow paths whose height is proportional to flow distance but fastest with traditional straight line 2D flows. In our second and third experiment we compared flat maps, 3D globes and a novel interactive design we call MapsLink, involving a pair of linked flat maps. We find that participants took significantly more time with MapsLink than other flow maps while the 3D globe with raised flows was the fastest, most accurate, and most preferred method. Our work suggests that careful use of the third spatial dimension can resolve visual clutter in complex flow maps.