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Objective To study the efficacy and safety of secukinumab in the treatment of moderate and severe plaque psoriasis in children. Methods A total of 10 children with psoriasis were enrolled at Yongcheng Central Hospital from November 2021 to November 2022. All patients were treated with subcutaneous injection of secukinumab and followed up for 52 weeks. The psoriasis area and severity index (PASI) and childrens' dermatology life quality index(CDLQI) were evaluated, and adverse reactions were observed. Results After 4 weeks of the treatment, 8 patients achieved PASI 75, among which 7 patients achieved PASI 90 and PASI 100 was observed in 5 patients. After 8 weeks of the treatment, all 10 patients reached PASI 75, including 8 patients with PASI 100. After 12 weeks, all 10 patients achieved PASI 100. By 52 weeks, 9 patients reached PASI 75, including 8 patients with PASI 90 and 7 patients with PASI 100. After 4 weeks of the treatment, CDLQI scores were significantly decreased and declined to 0 by 52 weeks. No adverse reactions were observed in all patients. Conclusions Secukinumab can rapidly improve moderate to severe plaque psoriasis in children and exhibits long-lasting benefit. It is safe and can quickly improve the quality of life of the children.

In order to identify the pathogen that caused rust of Bletilla striata in Guangxi Zhuang Autonomous Region and to screen resistance resources for B. striata, the rust pathogen was isolated from infected leaves of B. striata and identified using morphology and molecular methods. At the same time, the resistance of 23 B. striata from different regions was evaluated by artificial inoculation of pathogen. The results were as follows: (1) The urediopores of strain X2 isolated from diseased leaves in B. striata were golden yellow, oval, (21.43-30.95) μm × (13.10-19.05) μm. The teleutospores were golden yellow, obovate or clavate, (17.25-30) μm × (5.5-6.65) μm. (2) The length of ITS sequence of strain X2(OQ826009) was 689 bp, which were compared with other ITS sequences in the GenBank, and the similarity reached 95.86% compared with Coleosporium sp. (KY783686.1). But the phylogenetic tree showed that the sequence was clustered together with two sequences of Coleosporium bletiae (MN108161.1, OP363680.1). The strain X2 was identified as Coleosporium bletiae by combining morphology and molecular methods. (3) After 14 days of artificial inoculation with strain X2, the disease index of 23 Bletilla striata ranged from 0 to 70.7. And the resistance of strain X2 from 23 B. striata were divided into six different levels according to the disease index. Among them, one immune materials was identified for the disease index was 0. Four highly resistant materials were identified for the disease index was 1.7-4.7. Six disease-resistant materials were identified for the disease index was 5.6-9.4. Five medium-resistant materials were identified for the disease index was 12.7-18.3. Five susceptible materials were identified for the disease index was 32.0-49.1 and two highly susceptible materials were identified for the disease index was 62.2-70.7. In conclusion, five materials (one immune material and four highly resistant materials) of B. striata from different places (Honghe City in Yunnan Province, Gongcheng County and Baise City in Guangxi Zhuang Autonomous Region, Zunyi City in Guizhou Province and Yichang City in Hubei Province, respectively) can be promoted directly or applied as parent materials for creating excellent germplasm to resist the rust in B. striata for they express immune or highly resistance. This study provides the basis for further research on pathogenesis and control of rust in B. striata.

In order to identify the pathogens that caused tuber rot in Bletilla striata and study the inhibiting effects of herbal extracts on pathogens, the pathogens that caused tuber rot of B. striata were isolated using usual tissue isolation the strains were identified by morphological and molecular biological techniques, and inhibiting effects of seven traditional Chinese medicine extracts on pathogen were observed. The results were as follows:(1) A total of fourteen fungi and four bacteria were isolated from diseased leaves, leaf sheaths and tubers. But only strain GF-1 caused disease, whose symptoms consistent with those in the field. The incidences of GF-1 disease reinoculated in the field and laboratory were both 100％. (2) GF-1 was identified as a member of Epicoccum, and its colonial morphology was a circular form, with white mycelium, prostrate on the medium, aerial, diaphragms and branches. There were conidia and chlamydospores. (3) At last, the sequence of internal transcribed spacer (ITS) region of GF-1 were analyzed, the length was 522 bp. The sequence was compared with other species in the GenBank and reached 99.62% similarity to Epicoccum sorghinum (MN493119.1) isolated form Sorghum, which was closer than others, including Epicoccum sorghinum (MF948994.1) isolated form leaves of Bletilla striata. (4) GF-1 could be fully inhibited when the medium contained 0.1-0.2 g·mL-1 extracts that extracted from seven traditional Chinese medicines, respectively. It also could be fully inhibited by 0.05 g·mL-1 of Cinnamomum cassia or Syringa oblate. In summary, the pathogen that caused tuber rot in Bletilla striata was identified as Epicoccum sorghinum. And GF-1 could be fully inhibited cultivated on the medium which contained 0.1-0.2 g·mL-1 herbal extracts, e.g.: Cinnamomum cassia, Syringa oblate, Cyclocarya paliurus, Bletilla striata, Houpoea officinalis, Illicium verum or Cnidium monnieri. The results provide theoretical references for the control of tuber rot of Bletilla striata.

Abstract Background C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce. Methods The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis. Results The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells. Conclusions Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway.Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR.Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect theTh17 milieu.Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38.Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.

Abstract Background Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). Methods Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. Results The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. Conclusions Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES‐associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP. Methods Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ‐binding transcriptional co‐activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens‐1 (ZO‐1), E‐cadherin, and transforming growth factor‐beta1 (TGF‐β1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO‐1, E‐cadherin, TGF‐β1, and Smad7 were measured by Western blot. Results Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF‐β1, ZO‐1, and E‐cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO‐1, E‐cadherin, and TGF‐β1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells. Conclusions Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF‐β1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

Gastric cancer (GC) is one of the most common neoplastic malignancies, which permutes a fourth of cancer-related mortality globally. RNA modification plays a significant role in tumorigenesis, the underlying molecular mechanism of how different RNA modifications directly affect the tumor microenvironment (TME) in GC is unclear. Here, we profiled the genetic and transcriptional alterations of RNA modification genes (RMGs) in GC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through the unsupervised clustering algorithm, we identified three distinct RNA modification clusters and found that they participate in different biological pathways and starkly correlate with the clinicopathological characteristics, immune cell infiltration, and prognosis of GC patients. Subsequently, univariate Cox regression analysis unveiled 298 of 684 subtype-related differentially expressed genes (DEGs) are tightly interwoven to prognosis. In addition, we conducted the principal component analysis to develop the RM_Score system, which was used to quantify and predict the prognostic value of RNA modification in GC. Our analysis indicated that patients with high RM_Score were characterized by higher tumor mutational burden, mutation frequency, and microsatellite instability which were more susceptible to immunotherapy and had a favorable prognosis. Altogether, our study uncovered RNA modification signatures that may have a potential role in the TME and prediction of clinicopathological characteristics. Identification of these RNA modifications may provide a new understanding of immunotherapy strategies for gastric cancer.

Abstract This study aims to develop and validate a novel prognostic model to estimate overall survival (OS) in nasopharyngeal carcinoma (NPC) patients based on clinical features and blood biomarkers. We assessed the model's incremental value to the TNM staging system, clinical treatment, and Epstein‐Barr virus (EBV) DNA copy number for individual OS estimation. We retrospectively analyzed 519 consecutive patients with NPC. A prognostic model was generated using the Lasso regression model in the training cohort. Then we compared the predictive accuracy of the novel prognostic model with TNM staging, clinical treatment, and EBV DNA copy number using concordance index (C‐index), time‐dependent ROC (tdROC), and decision curve analysis (DCA). Subsequently, we built a nomogram for OS incorporating the prognostic model, TNM staging, and clinical treatment. Finally, we stratified patients into high‐risk and low‐risk groups according to the model risk score, and we analyzed the survival time of these two groups using Kaplan–Meier survival plots. All results were validated in the independent validation cohort. Using the Lasso regression, we established a prognostic model consisting of 13 variables with respect to patient prognosis. The C‐index, tdROC, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort than did TNM staging, clinical treatment, and EBV DNA copy number. Nomogram consisting of the prognostic model, TNM staging, clinical treatment, and EBV DNA copy number showed some superior net benefit. Based on the model risk score, we split the patients into two subgroups: low‐risk (risk score ≤ −1.423) and high‐risk (risk score > −1.423). There were significant differences in OS between the two subgroups of patients. Similar results were observed in the validation cohort. The proposed novel prognostic model based on clinical features and serological markers may represent a promising tool for estimating OS in NPC patients.

China, through its open policy, has enhanced its cooperation with Africa through outward foreign direct investment (OFDI) in the region’s production capacity. Though China’s investment prospects in Africa remain vast and diversified, the continent constitutes a small share of the stock of Chinese global OFDI. There is a dearth of research on the relationship between the level of African investment facilitation and the scale of China’s investments in the continent. The paper provides a comprehensive measurement of investment facilitation in 19 African countries spanning the 2010 to 2017 period using the entropy weight method. The expanded investment gravity model analyzes the impact of African investment facilitation on China’s OFDI in the continent. Investment facilitation levels of most African countries are found to be relatively low, except for South Africa and Morocco. The empirical results support a significant and positive impact of investment facilitation in Africa on China’s OFDI. From a disaggregated investment facilitation perspective, the application of information technology is found to be significant for aiding China’s investments in Africa.

Precious non-noble metals have been constantly attracting research attention in order to realize an inexpensive, extra active and more stable electrocatalysts in terms of various oxidation states and structures for their applications in oxidation (splitting) of water. In the present work graphene oxide incorporated, MnO2-NiO composite metal oxide nanoflakes were synthesized on the stainless steel substrate using efficient electrodeposition route in alkaline media and drop casting method with further annealing treatment at 400 °C for 4 h. Initially MnO2-NiO nanoflakes were deposited using different cyclic sweep rates, later graphene oxide suspension was drop casted on the MnO2-NiO nanoflakes and subsequently subjected to annealing at 200 °C for 2 h. The prepared electrode material is denoted as GO/MnO2-NiO/SS and used as an electrocatalyst for oxygen evolution. Field emission scanning electron microscopy, transmission electron microscopy, Energy dispersive electron spectroscopy and X-ray diffraction spectroscopy were used to study the crystalline nature and morphologies of the deposited films. The electrochemical properties of the electrode material were investigated using cyclic voltammetry and linear sweep voltammetry. The electrode exhibits low overpotential and small Tafel slope of 379 mV and 47.84 mVdec−1 at the current density of 10 mA cm−2 in alkaline (KOH) medium. In addition, the electrode shows a long time stability of 28800 s. Hence, the present study suggests that the GO incorporated Mn-Ni bimetal oxide modified electrode is suitable electrode material for oxygen evolution reaction (OER), owing to its facile preparation, inexpensive, easy handling and high active nature. Keywords: MnO2, NiO, Graphene oxide, Electrodeposition, Alkaline solution, Annealing, OER

Abstract Asthma is a chronic and heterogeneous disease characterised by airway inflammation and intermittent airway narrowing. The key obstacle in the prevention and treatment of asthma has been our incomplete understanding of its aetiology and biological mechanisms. The ras homolog family member A (RhoA) of the Rho family GTPases has been considered to be one of the most promising and novel therapeutic targets for asthma. It is well known that RhoA/Rho‐kinases play an important role in the pathophysiology of asthma, including airway smooth muscle contraction, airway hyper‐responsiveness, β‐adrenergic desensitisation and airway remodelling. However, recent advances have suggested novel roles for RhoA in regulating allergic airway inflammation. Specifically, RhoA has been shown to regulate allergic airway inflammation through controlling Th2 or Th17 cell differentiation and to regulate airway remodelling through regulating mesenchymal stem cell (MSC) differentiation. In this review, we evaluate the literature regarding the recent advances in the activation of RhoA/Rho‐kinase, cytokine and epigenetic regulation of RhoA/Rho‐kinase, and the role of RhoA/Rho‐kinase in regulating major features of asthma, such as airway hyper‐responsiveness, remodelling and inflammation. We also discuss the importance of the newly identified role of RhoA/Rho‐kinase signalling in MSC differentiation and bronchial epithelial barrier dysfunction. These findings indicate the functional significance of the RhoA/Rho‐kinase pathway in the pathophysiology of asthma and suggest that RhoA/Rho‐kinase signalling may be a promising therapeutic target for the treatment of asthma.

Allergic rhinitis (AR) is an IgE-mediated upper airway disease, and its impact on asthma has been widely recognized. Protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) gene polymorphisms have been reported to be associated with several immune-related diseases. Here we investigated the reffect of these two genes’ polymorphisms on the risk of AR and asthma in Chinese Han children. A total of 106 AR patients, 112 AR with asthma patients, and 109 healthy children were enrolled in the study. The SNPs of PTPN22 (rs2488457, rs1310182, rs3789604) and CTLA-4 (rs3087243, rs11571302, rs11571315, rs231725, rs335219727, and rs4553808) were genotyped using a PCR-restriction fragment length polymorphism assay. For PTPN22, an increased prevalence of the CC genotype and C allele in rs1310182 were identified in AR group. For CTLA-4, AA genotype and A allele in rs3087243 and rs231725 were increased in AR with asthma group while in AR group, AA genotype and A allele in rs231725 were obviously decreased. This study reveals a significant association between SNPs in PTPN22, CTLA-4 gene and AR with asthma in Chinese Han children, which might be susceptibility factors for AR and asthma.

Tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms have been reported to be associated with the susceptibility to several immune-related diseases. Here we investigated the effect of TNFAIP3 gene polymorphisms on the risk of allergic rhinitis (AR) in a Chinese Han population. The case-control study included 540 AR patients and 524 healthy controls. Genotyping for TNFAIP3 polymorphisms (rs5029928, rs9494885, rs10499194, rs610604, and rs7753873) were performed using restriction fragment length polymorphism analysis and DNA sequencing. Allele and genotype frequencies were compared between patients and controls. The rs9494885 TC genotype (corrected p (p=0.0032); odds ratio (OR)=2.06, 95% confidence intervals (CI): 1.40-3.04) and C allele (p=0.0056; OR=1.94, 95% CI: 1.35-2.76) were more frequent in AR patients compared with controls. The frequencies of the rs9494885 TT genotype (p=0.0029; OR=0.49, 95% CI: 0.33-0.72) and T allele (p= 0.0056; OR=0.52, 95% CI: 0.36-0.74) were lower in AR patients than that in controls. A higher frequency of the rs7753873 AC genotype (p=0.0023; OR=1.96, 95 %CI: 1.38-2.77) and C allele (p=0.0012; OR=1.74, 95% CI: 1.26-2.40) and a lower frequency of the rs7753873 AA genotype (p=0.0040; OR=0.53, 95% CI: 0.38-0.75) and A allele (p=0.0012; OR=0.58, 95% CI: 0.42-0.80) were observed in AR patients. TNFAIP3 gene polymorphisms (rs9494885 and rs7753873) are associated with the susceptibility to AR in the Chinese Han population.

BACKGROUND:Heredity and environmental exposures may contribute to a predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory gene, has recently been reported to play a role in autoimmune diseases. OBJECTIVE:This study was performed to evaluate the potential association of FCRL3 polymorphisms with AR in a Chinese Han population. METHODS:Five single-nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele, genotype and haplotype frequencies were compared between patients and controls using the χ2 test. The online software platform SHEsis was used to analyze their haplotypes. RESULTS:This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a significantly increased prevalence of the AA genotype and A allele in AR patients was recorded. The frequency of the GG genotype and G allele of rs10489678 was markedly higher in AR patients than those in controls. For rs7522061, a higher frequency of the TT genotype, and a lower frequency of the CT genotype were found in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a higher frequency of G allele were observed in AR patients. According to the analysis of the three strong positive SNPs, the haplotype of AGT increased significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29 × 10(-14), OR [95% CI] 1.978 [1.652~2.368]). CONCLUSIONS:This study found a significant association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The results suggest these gene polymorphisms might be the autoimmunity risk for AR.

Tumor angiogenesis is a complex process based upon a sequence of interactions between tumor cells and endothelial cells. Previous studies have shown that CD147 was correlated with tumor angiogenesis through increasing tumor cell secretion of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). In this study, we made a three-dimensional (3D) tumor angiogenesis model using a co-culture system of human hepatocellular carcinoma cells SMMC-7721 and humanumbilical vein endothelial cells (HUVECs) in vitro. We found that CD147-expressing cancer cells could promote HUVECs to form net-like structures resembling the neo-vasculature, whereas the ability of proliferation, migration and tube formation of HUVECs was significantly decreased in tumor conditioned medium (TCM) of SMMC-7721 cells transfected with specific CD147-siRNA. Furthermore, by assaying the change of pro-angiogenic factors in TCM, we found that the inhibition of CD147 expression led to significant decrease of VEGF and insulin-like growth factor-I (IGF-I) secretion. Interestingly, we also found that IGF-I up-regulated the expression of CD147 in both tumor cells and HUVECs. These findings suggest that there is a positive feedback between CD147 and IGF-I at the tumor-endothelial interface and CD147 initiates the formation of an angiogenesis niche.