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Abstract Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

Abstract Angiogenesis is the process of new blood vessel growth from pre‐existing ones involving vascular endothelial cell activation, proliferation, migration, and tube formation. The vascular endothelial growth factor A (VEGF‐A) is known to be a key factor that promotes angiogenesis. Pathological angiogenesis is a key and common feature of numerous ocular neovascular diseases, such as wet age‐related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, and corneal neovascularization. Although anti‐VEGF treatment has been a great success for the treatment of such ocular neovascular diseases, many challenges exist, such as limited efficacy, unresponsiveness in many patients, drug resistance, treatment burden due to repeated intravitreous injection, all of which incent much effort and enthusiasm to find new and better treatment for ocular neovascular diseases. In recent years, new antiangiogenic drug, targets and drug delivery methods have been developed. This perspective discusses the status of currently available therapies, challenges, opportunities, and potential new directions toward better therapies for ocular neovascular diseases.

To reveal the changes in the supply efficiency of forest farm ecological products after the reform of state-owned forest farms, this study uses the ecological product accounting method to calculate the physical quantity and value of state-owned forest farm ecological products using data from 2015 and 2020. Through exploratory spatial data analysis, the spatial distribution of the supply efficiency of ecological products of state-owned forest farms and its primary index are studied to explore the temporal and spatial evolution of ecological products from state-owned forest farms in China. The results show the following: (1) Through the reform of state-owned forest farms, the supply capacity of forest farms’ ecological products has been greatly improved, and the physical quantity and value quantity of ecological products have shown an increasing trend, with growth rates of 31.7% and 24.2%, respectively. (2) There is strong spatial heterogeneity in the supply efficiency of ecological products from state-owned forest farms in various provinces, and the overall distribution pattern is gradually decreasing from the northwest to the southeast coastal provinces. (3) There is a negative correlation between the supply capacity of ecological products and provincial GDP. The supply capacity of ecological products in provinces with high per capita GDP is relatively low. (4) The comprehensive index of the supply efficiency of ecological products and its first-level index of state-owned forest farms are characterized by different degrees of agglomeration in space, which are mainly represented by three distribution modes: “H–H”, “L–L”, and “L–H”. Therefore, it is necessary to clarify the ecological function orientation of state-owned forest farms, improve the endogenous power of ecological product supply, actively explore and connect social ecological needs, and achieve coordinated progress in terms of ecological environmental protection and economic development.

The major challenges for density maps estimation and accurate counting stem from the large-scale variations, serious occlusions, and perspective distortions. Existing methods generally suffer from the blurred density maps, which are caused by average convolution kernel, and the ineffective estimation across different crowd scenes. In this paper, we propose a multi-scale fusion conditional generative adversarial network (MFC-GAN) that can generate high-resolution and high-quality density maps. The fusion module of MFC-GAN is embedded in a multi-scale generator and discriminator architecture with a novel adversarial loss, which is designed to guide high-resolution density maps generation. In order to address the problem of scale variation, we further propose a bidirectional fusion module. It combines deep global semantic features and shallow local information by leveraging feature maps presented in different layers of the generator. Furthermore, in order to increase the effectiveness of the multi-scale fusion, we design a cross-attention fusion module, which weights the multi-scale fused feature and learns context-aware feature maps for generating high quality density maps. The experiments on four challenging datasets show the effectiveness, feasibility and robustness of the proposed MFC-GAN.

Summary: Endothelial cells (ECs) harbor distinct phenotypical and functional characteristics depending on their tissue localization and contribute to brain, eye, lung, and muscle diseases such as dementia, macular degeneration, pulmonary hypertension, and sarcopenia. To study their function, isolation of pure ECs in high quantities is crucial. Here, we describe protocols for rapid and reproducible blood vessel EC purification established for scRNA sequencing from murine tissues using mechanical and enzymatic digestion followed by magnetic and fluorescence-activated cell sorting.For complete details on the use and execution of these protocol, please refer to Kalucka et al. (2020), Rohlenova et al. (2020), and Goveia et al. (2020).

Summary: Endothelial cells (ECs) exhibit phenotypic and functional tissue specificities, critical for studies in the vascular field and beyond. Thus, tissue-specific methods for isolation of highly purified ECs are necessary. Kidney, spleen, and testis ECs are relevant players in health and diseases such as chronic kidney disease, acute kidney injury, myelofibrosis, and cancer. Here, we provide tailored protocols for rapid and reproducible EC purification established for scRNA sequencing from these adult murine tissues using the combination of magnetic- and fluorescence-activated cell sorting.For complete details on the use and execution of these protocols, please refer to Kalucka et al. (2020) and Dumas et al. (2020).

Summary: Endothelial cells (ECs) from the small intestine, colon, liver, and heart have distinct phenotypes and functional adaptations that are dependent on their physiological environment. Gut ECs adapt to low oxygen, heart ECs to contractile forces, and liver ECs to low flow rates. Isolating high-purity ECs in sufficient quantities is crucial to study their functions. Here, we describe protocols combining magnetic and fluorescent activated cell sorting for rapid and reproducible EC purification from four adult murine tissues.For complete details on the use and execution of these protocols, please refer to Kalucka et al. (2020).

The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy.

Coverless image steganography typically extracts feature sequences from cover images to map information. Once the extracted features have high similarity, it is challenging to construct a complete mapping sequence set, which places a heavy burden on the underlying storage and computation. In order to improve database utilization while increasing the data-hiding capacity, we propose a coverless steganography model based on low-similarity feature selection in the DCT domain. A mapping algorithm is presented based on an 8000-dimensional feature termed CS-DCTR extracted from each image to convert into binary sequences. The high feature dimension leads to a high capacity, ranging from 8 to 25 bits per image. Furthermore, scrambling is employed for feature mapping before building an inverted index tree, considerably enhancing security against steganalysis. Experimental results show that CS-DCTR features exhibit high diversity, averaging 49.3% complete mapping sequences, which indicates lower similarity among CS-DCTR features. The technique also demonstrates resistance to normal operations and benign attacks. The information extraction accuracy rises to 96.7% on average under typical noise attacks. Moreover, our technique achieves excellent performance in terms of hiding capacity, image utilization, and transmission security. [ABSTRACT FROM AUTHOR]

The aim of this study is to consider the economic, resource, energy and environmental factors in a low-carbon economic efficiency evaluation system and to analyze the factors affecting iron and steel enterprises. A combined data envelopment analysis and Malmquist index model have been used in this paper. We empirically investigate the low-carbon efficiency of the Chinese steel industry using observations of 17 listed enterprises from 2009 to 2013. The results show that the economic efficiency of China's iron & steel enterprises is generally low. The Malmquist productivity index also shows a decreasing trend. Based on our findings, some policies are proposed to improve the low-carbon economic efficiency of China's steel industry. [ABSTRACT FROM AUTHOR]