Abstract
Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing ...single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4
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T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4
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T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.
The COVID-19 pandemic has led to worldwide school closures, with millions of children confined to online learning at home. As a result, children may be susceptible to anxiety and digital eye strain, ...highlighting a need for population interventions.
The objective of our study was to investigate whether a digital behavior change intervention aimed at promoting physical activity could reduce children's anxiety and digital eye strain while undergoing prolonged homeschooling during the COVID-19 pandemic.
In this cluster randomized controlled trial, homeschooled grade 7 students at 12 middle schools in southern China were recruited through local schools and randomly assigned by the school to receive (1:1 allocation): (1) health education information promoting exercise and ocular relaxation, and access to a digital behavior change intervention, with live streaming and peer sharing of promoted activities (intervention), or (2) health education information only (control). The primary outcome was change in self-reported anxiety score. Secondary outcomes included change in self-reported eye strain and sleep quality.
On March 16, 2020, 1009 children were evaluated, and 954 (94.5%) eligible children of consenting families were included in the intention-to-treat analysis. Children in the intervention (n=485, 6 schools) and control (n=469, 6 schools) groups were aged 13.5 (SD 0.5) years, and 52.3% (n=499) were male. The assigned interventions were completed by 896 children (intervention: n=467, 96.3%; control: n=429, 91.5%). The 2-week change in square-root-transformed self-reported anxiety scores was greater in the intervention (-0.23, 95% CI -0.27 to -0.20) vs control group (0.12, 95% CI 0.09-0.16; unadjusted difference -0.36, 95% CI -0.63 to -0.08; P=.02). There was a significant reduction in square-root-transformed eye strain in the intervention group (-0.08, 95% CI -0.10 to 0.06) compared to controls (0.07, 95% CI 0.05-0.09; difference -0.15, 95% CI -0.26 to -0.03; P=.02). Change in sleep quality was similar between the two groups.
This digital behavior change intervention reduced children's anxiety and eye strain during COVID-19-associated online schooling.
ClinicalTrials.gov NCT04309097; http://clinicaltrials.gov/ct2/show/NCT04309097.
In the current era, as modern cities increasingly face environmental disasters and inherent challenges, the creation and enhancement of resilient cities have become critical. China’s urban resilience ...exhibits significant imbalances and inadequacies at the provincial level. This study delves into the evolution of urban resilience in various Chinese provinces, offering valuable insights for building and nurturing resilient cities. Initially, a comprehensive evaluation system for China’s urban resilience was established, incorporating 24 indicators across three key resilience aspects: resistance, adaptability, and recovery. The entropy weight method was used to develop an urban resilience evaluation model, and the Moran index and spatial cold–hot-spot analysis were applied to examine the spatiotemporal dynamics of urban resilience across China’s 31 provinces from 2012 to 2021. Moreover, the geographically and temporally weighted regression model was employed to analyze the spatial distribution of factors affecting urban resilience. The results show a general upward trend in urban resilience across Chinese provinces, with notable regional differences and concentrations. A significant decrease in urban resilience is observed from southeastern coastal cities to inland regions. The regression model highlights spatial variations in the impact of different factors, with the same factor having varying effects in different provinces. This research provides a thorough understanding of the factors influencing urban resilience in China, contributing to both theoretical and practical discussions on the topic. It lays a strong scientific groundwork for the development and advancement of resilient cities in China.
Nanocomposite dental resins with 0, 2, 5, and 10 wt % methacryl polyhedral oligomeric silsesquioxane (POSS) as filler in the resin matrix were prepared by a light curing method.The atomic force ...microscopy (AFM), fourier transform infrared spectroscopy (FTIR), nanoindentation, and nanoscratch tests were carried out to study the effect of POSS contents on the compatibility, double bond conversion, volumetric shrinkage, hardness, modulus, and resistance of the dental resins. POSS was very uniformly dispersed and showed a good compatibility with the matrix. The double bond conversion increased and the volume reduced with the addition of POSS. As the POSS addition increased, the mechanical properties increased initially. Small addition of POSS remarkably enhanced the hardness and scratch resistance of the resin matrix.
Road intersections are essential to road networks. How to precisely recognize road intersections based on GPS data is still challenging in intelligent transportation systems. Road intersection ...recognition involves detecting intersections and recognizing its scope. There are few works on intersections’ scope recognition. The existing methods always focus on road intersection detection. It includes two parts: one is selecting turning points from GPS data and extracting their geometric features, another is clustering them into center coordinates of road intersections. However, the accuracy of road intersection detection still has improvement room due to two drawbacks: (1) Besides geometric features, spatial features explored from GPS data and the interactions among all features are also important to represent intersections’ semantics more accurately, and (2) How to capture the points around intersections for clustering has great impact on the accuracy of intersection detection. To solve the preceding problems, we propose a novel approach for road intersection recognition via combining a classification model and clustering algorithm based on GPS data, which involves detecting the center coordinate and computing the radius of the intersection. Firstly, we distil geometric features and spatial features from historical GPS points. These features are inputted into the Extreme Deep Factorization Machine (xDeepFM) model which is applied for capturing the GPS points nearby road intersections. Secondly, the preceding points are clustered into center coordinates of road intersections by the Density-Based Spatial Clustering of Applications with Noise algorithm (DBSCAN). Thirdly, we present a new method of radius computing by integrating Delaunay triangulation with circle shape structure. Experiments are carried out on the GPS data of Chengdu, China. Compared with some state-of-the-art methods, our approach achieves higher accuracy on road intersection recognition based on GPS data. The precision, recall, and f-measure of our proposed center coordinates detection method are respectively 99.0%, 92.7%, and 95.8% when the matching area’s radius is 30 m. Moreover, the error of the proposed radius calculation method is less than 26.5%.
Abstract
FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2
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tumors are unavailable. Here we show that FGF-2 ...modulates tumor vessels by recruiting NG2
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pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2
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tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2
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breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
Electron probe microanalysis (EPMA) is promising for accurately determining elemental components in micro-areas of individual phytolith particles, interpreting compositional features and formation ...mechanisms of phytoliths in plants, identifying archeological and sedimental phytolith. However, the EPMA method of analyzing mounted slide phytoliths has not well been defined. In this study, we attempted different EPMA methods to determine the elemental compositions of phytoliths in mounted slides. Direct analysis of carbon (DAC) with other elements in phytolith could obtain abnormally high total values and carbon values. The method of carbon excluded in measuring elements (non-carbon analysis (NCA)) was feasible to obtain elemental compositions in phytolith. The NCA method was conducive to obtain the factual elemental compositions of an individual phytolith (morphotype) when the carbon content of phytolith was relatively low. The EPMA results of phytoliths from 20 bamboo species (three genera) showed that phytolith was dominantly composed of SiO.sub.2 but also included low contents of diverse other elements. The EPMA of phytoliths can provide the elemental composition of micro-areas of an individual phytolith particle. The elemental compositions of phytolith varied with their morphotypes, the genera and ecotype of bamboos. The EPMA of elemental compositions in phytoliths is a potential tool to study the formation mechanism of phytoliths, plant taxonomical identification, archaeological and paleoenvironmental reconstruction.
The proliferation and epithelial–mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells are the major pathological changes in development of proliferative vitreoretinopathy (PVR), ...which leads to severe visual impairment. Histone deacetylases (HDACs)‐mediated epigenetic mechanisms play important roles in controlling various physiological and pathological events. However, whether HDACs are involved in the regulation of proliferation and EMT in PRE cells remains unidentified. In this study, we evaluated the expression profile of HDAC family (18 genes) and found that some of class I and class II HDACs were up‐regulated in transforming growth factor‐β2 (TGF‐β2)/TGF‐β1‐stimulated RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of cyclin/CDK/p‐Rb and induction of p21 and p27. In the meantime, TSA strongly prevented TGF‐β2–induced morphological changes and the up‐regulation of α‐SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also demonstrated that TSA affected not only the canonical Smad signalling pathway but also the non‐canonical TGF‐β/Akt, MAPK and ERK1/2 pathways. Finally, we found that the underlying mechanism of TSA affects EMT in RPE cells also through down‐regulating the Jagged/Notch signalling pathway. Therefore, this study may provide a new insight into the pathogenesis of PVR, and suggests that epigenetic treatment with HDAC inhibitors may have therapeutic value in the prevention and treatment of PVR.
Zwitterionic wormlike micelles with AuCl4(-) counterions were fabricated for the first time as the soft templates for colloidal synthesis of gold nanowire networks; gold-based alloy nanowire networks ...were also achieved using mixed wormlike micelles as soft templates.
Complexities of heating mechanisms make it difficult to investigate the safety of a polymer bonded explosive (PBX) charge of earth-penetrating-weapons (EPWs) during penetration. In this paper, the ...dynamic damage and non-shock initiation of PBX1314 (60 wt % hexahydro-1, 3, 5-trinitro-1, 3, 5-s-triazine (RDX), 16 wt % aluminum, 24 wt % hydroxy-terminated polybutadiene (HTPB)) during penetration is investigated through experiments and simulations. In the experiments, steel projectiles filled with PBX1314 are launched to penetrate concrete targets. In the results, non-shock initiations occur on the tail surface of PBX1314 along with mechanical damage of the tail and middle part of PBX1314. A dynamic damage and initiation model is proposed to characterize the effects of microcracks on the mechanical and thermal responses of PBX1314. Investigation based on the model suggests that microcrack interfacial friction plays significant roles in damage, heat generation and localization in PBX1314. A non-shock initiation criterion is developed based on macroscale variables in PBX1314. Numerical simulations of the penetration experiments are performed by using the proposed model and criterion. The mechanical damage and non-shock initiation of PBX1314 in the experiments are successfully predicted. The simulation results indicate that the tail of PBX1314 impacts the projectile repeatedly during penetration. Finally, the initiation criterion is satisfied because of frictional heat localization near microcrack surfaces and initiation is activated in the tail of PBX1314.
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