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Endoglin (ENG) mutation causes type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22αCre leads to AVM development in the brain and other organs. We hypothesized that an increase in Eng- negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon-improved cre (icre), which is more potent in recombination of the floxed alleles than the wild-type (WT) cre. R26RCreER;Engf/f mice that have a Rosa promoter driving and tamoxifen (TM)-inducible WT cre expression globally, and PdgfbiCreER;Engf/f mice that have a Pdgfb promoter driving and TM-inducible icre expression in ECs were treated with three intra-peritoneal injections of TM (2.5 mg/25 g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that icre caused more Eng deletion in the brain, indicated by a lower level of Eng proteins (p < 0.001) and fewer Eng-positive ECs (p = 0.01) than mice with WT cre. Mice with icre-mediated Eng deletion have more abnormal vessels (p = 0.02), CD68+ macrophages (p = 0.002), and hemorrhage (p = 0.04) and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that has not been detected in WT cre mice before. RNA-seq analysis showed that 8 out of the 10 top upregulated pathways identified by gene ontology (GO) analysis are related to inflammation. Therefore, the increase in Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng-negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

We have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) could Alk1- mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1- ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM from PdgfbiCreER;Alk12f/2f mice (EC-specific tamoxifen-inducible Cre with Alk1-floxed alleles) into wild-type mice, and then induced bAVMs by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor and intra-peritoneal injection of tamoxifen. For the second question, clonal expansion was analyzed using PdgfbiCreER;Alk12f/2f;confetti+/- mice. For the third question, we titrated tamoxifen to limit Alk1 deletion and compared the severity of bAVM in mice treated with low and high tamoxifen doses. We found that wild-type mice with PdgfbiCreER;Alk12f/2f BM developed bAVMs upon VEGF stimulation and Alk1 gene deletion in BMDECs. We also observed clusters of ECs expressing the same confetti color within bAVMs and significant proliferation of Alk1- ECs at early stage of bAVM development, suggesting that Alk1- ECs clonally expanded by local proliferation. Tamoxifen dose titration revealed a direct correlation between the number of Alk1- ECs and the burden of dysplastic vessels in bAVMs. These results provide novel insights for the understanding of the mechanism by which a small fraction of Alk1 or endoglin mutant ECs contribute to development of bAVMs.

Due to the sanctions imposed on Russia in 2022, the broadcasting of state-owned Russian TV channels was banned in many countries. In response to the changing media environment, Russian TV companies are compelled to explore new markets worldwide to provide information about the Russian Federation. The authors identify China as a key alternative to the lost markets, given the booming Chinese media industry that offers a variety of news consumption options to the audience. Among these options, short online videos have gained significant popularity, with Douyin emerging as one of the most successful short-video platforms. This article analyzes the evolution of this phenomenon in the People’s Republic of China (PRC) and aims to observe the reasons behind the format’s popularity among the Chinese audience. The relevance of this paper lies in the necessity to study effective and legitimate methods of news production on Chinese internet platforms for Russian TV companies. Analyzing a total of 5765 posts, the authors focus on the topics, length, and content creation methods used by three television companies (CCTV, Henan TV, Shanghai Dragon TV) when posting news on the social media platform Douyin. Additionally, a review of the regulations governing the work of Chinese and foreign media in China has been carried out. The study describes the distinctive features and development strategies of the accounts of these TV channels and concludes with recommendations that Russian media can utilize in adapting news content for well-known Chinese online platforms. Статья посвящена анализу феномена коротких онлайн-видео в Китае. Исследуются основные характеристики и причины популярности такого способа потребления актуальной информации у китайской аудитории. Особое внимание уделяется опыту размещения телекомпаниями КНР новостного аудиовизуального контента в формате short video на платформе Douyin. В основу положен тезис о том, что китайский рынок сетевых СМИ является важной альтернативой для российских медиа в связи с введением запрета на распространение новостей государственными средствами массовой информации РФ после начала СВО на Украине в целом ряде стран. Актуальность исследования обусловлена необходимостью изучения эффективных и легитимных методов работы с новостной продукцией в цифровой среде КНР, которая существует в условиях контроля со стороны властей. Выполнен обзор нормативных актов, регулирующих работу китайских и иностранных СМИ в Китае. Представлены результаты контент-анализа новостных роликов, публикуемых телекомпаниями CCTV, Dragon TV и Henan Television на платформе Douyin. Описаны отличительные особенности и стратегии развития аккаунтов указанных телеканалов. Выявлены рекомендации, которые могут быть использованы российскими СМИ в процессе адаптации новостного контента на известных китайских онлайн-платформах.

ObjectiveA high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.MethodsBrain AVMs were induced in adult mice in which activin receptor-like kinase 1 (Alk1, a gene that causes AVM) gene exons 4-6 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce Alk1 mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 × 109 [high] or 2 × 109 [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.ResultsCompared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue-positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.ConclusionsUsing mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.

Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. The pathogenesis of bAVM has not been fully understood. Animal models are important tools for dissecting bAVM pathogenesis and testing new therapies. We have developed several mouse bAVM models using genetically modified mice. However, due to the body size, mouse bAVM models have some limitations. Recent studies identified somatic mutations in sporadic human bAVM. To develop a feasible tool to create sporadic bAVM in rodent and animals larger than rodent, we made tests using the CRISPR/Cas9 technique to induce somatic gene mutations in mouse brain in situ. Two sequence-specific guide RNAs (sgRNAs) targeting mouse Alk1 exons 4 and 5 were cloned into pAd-Alk1e4sgRNA + e5sgRNA-Cas9 plasmid. These sgRNAs were capable to generate mutations in Alk1 gene in mouse cell lines. After packaged into adenovirus, Ad-Alk1e4sgRNA + e5sgRNA-Cas9 was co-injected with an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) into the brains of wild-type C57BL/6J mice. Eight weeks after viral injection, bAVMs were detected in 10 of 12 mice. Compared to the control (Ad-GFP/AAV-VEGF-injected) brain, 13% of Alk1 alleles were mutated and Alk1 expression was reduced by 26% in the Ad-Alk1e4sgRNA + e5sgRNA-Cas9/AAV-VEGF-injected brains. Around the Ad-Alk1e4sgRNA + e5sgRNA-Cas9/AAV-VEGF injected site, Alk1-null endothelial cells were detected. Our data demonstrated that CRISPR/Cas9 is a feasible tool for generating bAVM model in animals.

ObjectiveA high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.MethodsBrain AVMs were induced in adult mice in which activin receptor-like kinase 1 (Alk1, a gene that causes AVM) gene exons 4-6 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce Alk1 mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 × 109 [high] or 2 × 109 [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.ResultsCompared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue-positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.ConclusionsUsing mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.

X65 carbon steel is widely used in subsea gathering and transportation pipelines. In the gathering and transportation process, the natural gas medium is complex and often contains corrosive gases such as H2S and CO2. Due to the use of wet gas transportation, condensate water was formed, resulting in serious corrosion perforation accidents of pipelines. In this work, through the experiments of high - temperature and high - pressure reactor, the corrosion mechanism of gas phase, liquid phase and gas - liquid interface were analyzed, which provided a basis for the formulation of corrosion prevention and control measures for X65 steel wet gas gathering and transmission pipeline. Moreover, high - temperature and high - pressure reactor experiments were carried out with X65 steel in the presence of CO2, H2S and Cl - respectively. Each experiment was carried out for 7 d for gas - liquid interface corrosion, and the characteristics of corrosion products were analyzed by surface analysis technologies, such as scanning electron microscope (SEM) and X - ray diffraction (XRD). Results showed that with the injection of CO2 and H2S, the local corrosion rate increased in three regions of gas phase, liquid phase, and gas - liquid interface. In the presence of CO2 and H2S, the order of corrosion rate was liquid phase corrosion rate > gas phase corrosion rate > interface corrosion rate. Under the condition of gas - liquid interface, X65 steel formed anode below the interface and cathode above the interface, so that the local corrosion rate of liquid phase was faster.

In the past, the structures of conventional direct current (DC) and flexible DC transmission projects were end-to-end or multi-terminal radiation. The corresponding stability control system uses the converter electric quantity and pole emergency switch off (ESOF) signal as the criterion of pole blocking. It is not suitable for the application of flexible DC power transmission engineering with ring structure, because the DC converter blocking failure cannot be identified reliably. According to the development experience of stability control system of Zhangbei voltage source converter based high voltage direct current(VSC-HVDC) transmission project, a new improved method of DC pole blocking detection is proposed in this paper for stability control. This criterion adopts the characteristic signal of DC control and protection as the main judgment object when DC light load is applied, and adopts the characteristic signal of DC control and protection combined with the converter electric quantity as the main judgment object when the DC power is above 10% of rated power. The improved detection is applicable to both HVDC transmission projects and ring structure flexible DC transmission projects. At the same time, the calculation method of stability control measures of Zhangbei VSC-HVDC transmission project is proposed, which provides a reference for the application of subsequent flexible DC transmission projects and HVDC transmission projects. Theoretical analysis and real-time digital simulation system (RTDS) experiment verifies the reliability of the criterion.

Background and purposeBrain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model.MethodsbAVMs were induced through induction of brain focal activin-like kinase 1 (Alk1, an AVM causative gene) gene deletion and angiogenesis in adult Alk1-floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain.ResultsThalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68+ cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide.ConclusionsThalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression.