125 research outputs found
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, 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
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
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
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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
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A distinctive Eocene Asian monsoon and modern biodiversity resulted from the rise of eastern Tibet
The uplift of eastern Tibet, Asian monsoon development and the evolution of globally significant Asian biodiversity are all linked, but in obscure ways. Sedimentology, geochronology, clumped isotope thermometry, and fossil leaf-derived numerical climate data from the Relu Basin, eastern Tibet, show at ∼50–45 Ma the basin was a hot (mean annual air temperature, MAAT, ∼27 °C) dry desert at low-elevation of 0.6 ± 0.6 km. Rapid basin rise to 2.0 ± 0.9 km at 45–42 Ma and to 2.9 ± 0.9 km at 42–40 Ma, with MAATs of ∼20 and ∼16 °C, respectively, accompanied seasonally varying increased annual precipitation to >1500 mm. From ∼39 to 34 Ma, the basin attained 3.5 ± 1.0 km, near its present-day elevation (∼3.7 km), and MAAT cooled to ∼6 °C. Numerically-modelled Asian monsoon strength increased significantly when this Eocene uplift of eastern Tibet was incorporated. The simulation/proxy congruence points to a distinctive Eocene Asian monsoon, quite unlike that seen today, in that it featured bimodal precipitation and a winter-wet regime, and this enhanced biodiversity modernisation across eastern Asia. The Paleogene biodiversity of Asia evolved under a continually modifying monsoon influence, with the modern Asian monsoon system being unique to the present and a product of a long gradual development in the context of an ever-changing Earth system
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 2nd Workshop on Maritime Computer Vision (MaCVi) 2024
The 2nd Workshop on Maritime Computer Vision (MaCVi) 2024 addresses maritime
computer vision for Unmanned Aerial Vehicles (UAV) and Unmanned Surface
Vehicles (USV). Three challenges categories are considered: (i) UAV-based
Maritime Object Tracking with Re-identification, (ii) USV-based Maritime
Obstacle Segmentation and Detection, (iii) USV-based Maritime Boat Tracking.
The USV-based Maritime Obstacle Segmentation and Detection features three
sub-challenges, including a new embedded challenge addressing efficicent
inference on real-world embedded devices. This report offers a comprehensive
overview of the findings from the challenges. We provide both statistical and
qualitative analyses, evaluating trends from over 195 submissions. All
datasets, evaluation code, and the leaderboard are available to the public at
https://macvi.org/workshop/macvi24.Comment: Part of 2nd Workshop on Maritime Computer Vision (MaCVi) 2024 IEEE
Xplore submission as part of WACV 202
Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia
ObjectiveAlthough extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia.MethodsTo address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV.ResultsOur findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure.ConclusionOur research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia
Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody
The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines
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