In Vivo Molecular Imaging in Retinal Disease

There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of ocular fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule upregulation, some novel imaging agents that target retinal endothelial molecules were generated. In vivo molecular imaging has a great potential to impact medicine by detecting diseases or screening disease in early stages, identifying extent of disease, selecting disease and patient-specific therapeutic treatment, applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future

Vascular Adhesion Protein 1 in the Eye

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1), a dual-function molecule with adhesive and enzymatic properties, is expressed on the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity and can be a prognostic biomarker. Recent evidence suggests that VAP-1 is an important therapeutic target for several inflammation-related ocular diseases, such as uveitis, age-related macular degeneration (AMD), and diabetic retinopathy (DR), by involving in the recruitment of leukocytes at sites of inflammation. Furthermore, VAP-1 plays an important role in the pathogenesis of conjunctival inflammatory diseases such as pyogenic granulomas and the progression of conjunctival lymphoma. VAP-1 may be an alternative therapeutic target in ocular diseases. The in vivo imaging of inflammation using VAP-1 as a target molecule is a novel approach with a potential for early detection and characterization of inflammatory diseases. This paper reviews the critical roles of VAP-1 in ophthalmological diseases which may provide a novel research direction or a potent therapeutic strategy

Vascular Adhesion Protein 1 in the Eye

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1), a dual-function molecule with adhesive and enzymatic properties, is expressed on the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity and can be a prognostic biomarker. Recent evidence suggests that VAP-1 is an important therapeutic target for several inflammation-related ocular diseases, such as uveitis, agerelated macular degeneration (AMD), and diabetic retinopathy (DR), by involving in the recruitment of leukocytes at sites of inflammation. Furthermore, VAP-1 plays an important role in the pathogenesis of conjunctival inflammatory diseases such as pyogenic granulomas and the progression of conjunctival lymphoma. VAP-1 may be an alternative therapeutic target in ocular diseases. The in vivo imaging of inflammation using VAP-1 as a target molecule is a novel approach with a potential for early detection and characterization of inflammatory diseases. This paper reviews the critical roles of VAP-1 in ophthalmological diseases which may provide a novel research direction or a potent therapeutic strategy

MapVision: CVPR 2024 Autonomous Grand Challenge Mapless Driving Tech Report

Autonomous driving without high-definition (HD) maps demands a higher level of active scene understanding. In this competition, the organizers provided the multi-perspective camera images and standard-definition (SD) maps to explore the boundaries of scene reasoning capabilities. We found that most existing algorithms construct Bird's Eye View (BEV) features from these multi-perspective images and use multi-task heads to delineate road centerlines, boundary lines, pedestrian crossings, and other areas. However, these algorithms perform poorly at the far end of roads and struggle when the primary subject in the image is occluded. Therefore, in this competition, we not only used multi-perspective images as input but also incorporated SD maps to address this issue. We employed map encoder pre-training to enhance the network's geometric encoding capabilities and utilized YOLOX to improve traffic element detection precision. Additionally, for area detection, we innovatively introduced LDTR and auxiliary tasks to achieve higher precision. As a result, our final OLUS score is 0.58

Multiple Rotation Averaging with Constrained Reweighting Deep Matrix Factorization

Multiple rotation averaging plays a crucial role in computer vision and robotics domains. The conventional optimization-based methods optimize a nonlinear cost function based on certain noise assumptions, while most previous learning-based methods require ground truth labels in the supervised training process. Recognizing the handcrafted noise assumption may not be reasonable in all real-world scenarios, this paper proposes an effective rotation averaging method for mining data patterns in a learning manner while avoiding the requirement of labels. Specifically, we apply deep matrix factorization to directly solve the multiple rotation averaging problem in unconstrained linear space. For deep matrix factorization, we design a neural network model, which is explicitly low-rank and symmetric to better suit the background of multiple rotation averaging. Meanwhile, we utilize a spanning tree-based edge filtering to suppress the influence of rotation outliers. What\u27s more, we also adopt a reweighting scheme and dynamic depth selection strategy to further improve the robustness. Our method synthesizes the merit of both optimization-based and learning-based methods. Experimental results on various datasets validate the effectiveness of our proposed method

Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity

Here, we show that vitamin E succinate (VES) acts as a degrader for the m6A RNA demethylase fat mass and obesity-associated protein (FTO), thus suppressing tumor growth and resistance to immunotherapy. FTO is ubiquitinated by its E3 ligase DTX2, followed by UFD1 recruitment and subsequent degradation in the proteasome. VES binds to FTO and DTX2, leading to enhanced FTO–DTX2 interaction, FTO ubiquitination, and degradation in FTO-dependent tumor cells. VES suppressed tumor growth and enhanced antitumor immunity and response to immunotherapy in vivo in mouse models. Genetic FTO knockdown or VES treatment increased m6A methylation in the LIF (Leukemia Inhibitory Factor) gene and decreased LIF mRNA decay, and thus sensitized melanoma cells to T cell–mediated cytotoxicity. Taken together, our findings reveal the underlying molecular mechanism for FTO protein degradation and identify a dietary degrader for FTO that inhibits tumor growth and overcomes immunotherapy resistance

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future

Whole Genome Expression Profiling and Signal Pathway Screening of MSCs in Ankylosing Spondylitis

The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways

TNF- α

Ankylosing spondylitis (AS) is an autoimmune disease with unknown etiology. Dysregulated mesenchymal stem cells (MSCs) apoptosis may contribute to the pathogenesis of autoimmune diseases. However, apoptosis of MSCs from patients with AS (ASMSCs) has not been investigated yet. The present study aims to assess the apoptosis of bone marrow-derived ASMSCs and to investigate the underlying mechanisms of altered ASMSCs apoptosis. We successfully induced the apoptosis of ASMSCs and MSCs from healthy donors (HDMSCs) using the combination of tumor necrosis factor alpha (TNF-α) and cycloheximide (CHX). We found that ASMSCs treated with TNF-α and CHX showed higher apoptosis levels compared to HDMSCs. During apoptosis, ASMSCs expressed significantly more TRAIL-R2, which activated both the death receptor pathway and mitochondria pathway by increasing the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3. Inhibiting TRAIL-R2 expression using shRNA eliminated the apoptosis differences between HDMSCs and ASMSCs by partially reducing ASMSCs apoptosis but minimally affecting that of HDMSCs. Furthermore, the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3 were comparable between HDMSCs and ASMSCs after TRAIL-R2 inhibition. These results indicated that increased TRAIL-R2 expression results in enhanced ASMSCs apoptosis and may contribute to AS pathogenesis

The late Eocene rise of SE Tibet formed an Asian ‘Mediterranean’ climate

Southeastern (SE) Tibet forms the transition zone between the high interior Tibetan Plateau and the lowlands of southwest China. So understanding the elevation history of SE Tibet, a biodiversity hotspot, enlightens our understanding of the interactions between tectonics, monsoon dynamics and biodiversity. Here we reconstruct the uplift history of the Markam Basin, SE Tibet, during the middle−late Eocene based on U − Pb dating, plant fossil assemblages, and stable and clumped isotope analyses. Our results suggest that the floor of the Markam Basin was at an elevation of 2.6 ± 0.9 km between 42 Ma and 39 Ma, where the mean annual air temperature (MAAT) was 13.2 ± 2.4 °C. The basin then rose rapidly to 3.8 (+0.6/−0.8) km before 36 Ma. Integrated with existing paleoelevation data, we propose that the high plateau boundary (∼3.0 km) of SE Tibet formed during the late Eocene. Numerical climate modeling with realistic paleo-landscapes shows that with the rise of SE Tibet, a Mediterranean-like climate developed in the region characterized by bi-modal precipitation with two wet seasons in boreal spring and autumn. The high topographic relief of SE Tibet, coupled with this distinctive Mediterranean-like climate system, helped develop the high biodiversity of the Hengduan Mountains