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Background Collateral growth plays an important role in the recovery of acute myocardial infarction. C1q/TNF-related protein-2 (CTRP2), a CTRP family member, showed some protective effects on cell survival. In this study, the relationship between CTRP2 and collateral growth was examined. Methods C57BL/6 mice were subjected to myocardial ischaemia/reperfusion (I/R), and the expression of CTRP2 and the effect of CTRP2 on infarction size, cardiac function and angiogenesis were examined. The ischaemic hindlimb model was also used to examine the effect of CTRP2. In vitro, CTRP2-mediated regulation of angiogenesis, AKT activation and VEGFR2 expression in endothelial cells was examined. The CTRP2 level associated with good collateral growth was observed in a cohort. Results I/R reduced CTRP2 expression, and intraperitoneal injection of recombinant CTRP2 protein improved infarction size, cardiac function and angiogenesis. Overexpression of CTRP2 promoted blood refusion and collateral growth in ischaemic hindlimb mice. In vitro, CTRP2 enhanced tube formation and migration in a dose-dependent manner, while CTRP2 increased AKT phosphorylation and VEGFR2 expression. In an observational clinical cohort, CTRP2 levels were significantly increased in patients with good collateral growth, and CTRP2 was negatively associated with poor collateral growth in patients. Conclusion CTRP2 improved cardiac function by promoting collateral growth by promoting AKT-VEGFR2.

When tunnels are constructed at shallow depths in areas with poor geological conditions, such as portal sections, valleys and hillsides in regions with granitic bedrock, considerable excavation-induced deformation of the surrounding rock may occur, potentially resulting in tunnel collapses. The main reason for these problems is the lack of understanding of the deformation mechanism and evolution of the soft granitic rock surrounding the tunnel and the adoption of inappropriate construction technology and methods. This article analyzes the deformation mechanism of the rock surrounding a shallow tunnel based on in situ monitoring data as a case study and suggests that certain measures should be taken to effectively control the deformation of the surrounding rock and to minimize the potential for tunnel collapse. The results show that the deformation of the granitic soil surrounding the tunnel can be divided into three stages: the rapid deformation stage, the slow deformation stage and the stabilization stage. Appropriate construction methods should be carefully selected to ensure safety during tunnel excavation in the first stage. To avoid secondary disasters caused by tunnel collapses, three treatment measures may be implemented as part of safety management: enhancing the monitoring of the surrounding rock deformation, adjusting the construction methods and optimizing the support systems. In particular, accurate monitoring data and timely information feedback play a vital role in tunnel construction. Therefore, engineers with considerable engineering experience and professional knowledge are needed to analyze the monitoring data and make accurate predictions of tunnel deformation to ensure that reasonable measures are taken in the process of shallow tunnel excavation.

The occurrence of debris flow hazards has great destructive effects on the life and property safety of the people. Many factors control its occurrence. The intuitionistic fuzzy sets-TOPSIS model is introduced to assess the risk level of debris flow in the Duba river watershed at first; secondly, the decisive matrix of the intuitionistic fuzzy sets is established, and the index weight coefficients are determined by using the entropy weight method, and then the weighed decisive matrix is obtained. Finally, the degree of membership at different levels is calculated. The risk level corresponding to the maximum degree of membership is regarded as the final assessment level. The conclusions are drawn, estimating that the risk level of debris flow hazards in the Duba river watershed based on the intuitionistic fuzzy sets-TOPSIS model is feasible when its results are compared with the actual investigation and Liu X.L model, and the model not only can reflect the risk level of debris flow hazards accurately, but also further determines the risk ranking of debris flow in four different gullies, so that it can provide a new method and thoughts to estimate the risk level of debris flow hazards in the future.

The aim of our study was to evaluate the relationship between the 24-h blood pressure (BP) profile, plasma NT-proBNP levels and left ventricular hypertrophy (LVH) in subjects with primary aldosteronism (PA) compared to patients with essential hypertension (EH). A total of 385 consecutive patients with PA [187 with aldosterone producing adenoma (APA) and 198 with idiopathic hyperaldosteronism (IHA)] and 385 patients with EH were matched based on age, sex, body mass index (BMI), BP values and duration of hypertension. Twenty-four-hour ambulatory BP monitoring (ABPM), plasma levels of NT-proBNP, left ventricular mass index (LVMI), and other clinical medical data were assessed in all patients. No differences in age, sex, BMI, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between groups. Nighttime systolic BP (130 ± 16 vs. 127 ± 17 mmHg, p

A modified pseudo-dynamic method is introduced in the paper at first, then geometric model of seismic stability on the waterfront rock slope considering the non-linear twin shear criterion is established. Finally the influence factors on the stability of rock slope are analyzed. The conclusions are drawn that the stability of rock slope decreases as the external loading $$q$$ , rock unit weight $$\gamma$$ , horizontal seismic acceleration coefficient $$k_{h}$$ and vertical seismic acceleration coefficient $$k_{v}$$ increases, and it increases as uniaxial compressive strength $$\sigma_{c}$$ , the water depth $$h_{1}$$ and parameters of rock mass properties $$m_{i}$$ and $$GSI$$ of rocks increases. These conclusions can provide great instruction significance for the future engineering design.

QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.

Poyang Lake is the largest freshwater lake in China. A series of semimetal samples in summer and winter seasons located in cites of Ruihong and Hukou in Poyang Lake were sampled, respectively. According to the experimental procedure, the acid volatile sulfides (AVS) in the series of residues were selective extracting after the elemental sulphur (ES) extracted from the sediment samples, and then titrated using iodine titration. Based on the series data of AVS got from the above mentioned cites, the distribution behaviors of AVS with depth at different seasons in the two sites were demonstrated as well.

Vascular calcification (VC) is a highly regulated ectopic mineral deposition process involving immune cell infiltration in the vasculatures, which has been recognized to be promoted by hypertension. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells as a potential inflammatory mediator of vascular injury. This study aims to examine whether OPN is involved in the regulation of macrophage activation and osteoclast formation in hypertensive subjects with VC. We firstly found an increased proportion of CD11c+CD163- pro-inflammatory peripheral monocytes in hypertensive subjects with VC compared to those without VC by flow cytometric analysis. Primary cultured macrophages from hypertensive subjects with VC also showed altered expression profile of inflammatory factors and higher serum OPN level. Exogenous OPN promoted the differentiation of peripheral monocytes into an alternative, anti-inflammatory phenotype, and inhibited macrophage-to-osteoclast differentiation from these VC patients. In addition, calcified vessels showed increased osteoclasts accumulation accompanied with decreased macrophages infiltration in the of hypertensive subjects. Taken together, these demonstrated that OPN exerts an important role in the monocytes/macrophage phenotypic differentiation from hypertensive patients with VC, which includes reducing inflammatory factor expression and attenuating osteoclast formation.

Background Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and Results In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P =0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. Conclusions Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

Perivascular adipose tissue (PVAT)-derived adiponectin (APN) is a secreted adipokine that protects against hypertension-related cardiovascular injury. However, the regulation of APN expression in hypertension remains to be explored. In this study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Complement 3-deficient hypertensive mice were protected from ANP decrease in the PVAT. APN deficiency blockaded the protective effects of complement inhibition against hypertensive vascular injury. Mechanistically, complement 5a (C5a)-induced TNF-α secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-α up-regulation and APN down-regulation in the PVAT of DOCA mice. Moreover, we detected increased macrophage infiltration and C5a expression associated with decreased APN expression in adipose tissue from patients with aldosterone-producing adenoma. These results identify a novel interaction between macrophages and adipocytes in the PVAT, where complement-mediated inhibition of APN acts as a potential risk factor for hypertensive vascular inflammation.-Ruan, C.-C., Ma, Y., Ge, Q., Li, Y., Zhu, L.-M., Zhang, Y., Kong, L.-R., Wu, Q-H., Li, F., Cheng, L., Zhao, A. Z., Zhu, D.-L., Gao, P.-J. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.

Objective Osteoglycin (OGN) has been noted for its implication in cardiovascular disease in recent studies. However, the relationship between OGN and angiogenesis remains unknown. Therefore, we aimed to investigate the effect of OGN on ischaemia-induced angiogenesis and to address the underlying mechanisms. Methods and results The expression of OGN was decreased in a limb ischaemia mouse model. OGN knockout (KO) mice were used to further understand the role of OGN after ischaemia. The perfusion recovery rate after femoral artery ligation was higher in OGN KO mice than in wild-type (WT) mice. The capillary density in the gastrocnemius muscle of the ischaemic limb was also higher in OGN KO mice. Moreover, ex vivo aortic ring explants from OGN KO mice exhibited stronger angiogenic sprouting than those from WT mice. In human umbilical vein endothelial cells (HUVECs), OGN knockdown enhanced endothelial cell (EC) activation, including tube formation, proliferation, and migration. In contrast, OGN overexpression inhibited HUVEC activation. Mechanistic studies revealed that OGN associates with vascular endothelial growth factor receptor 2 (VEGFR2) and negatively regulates the interaction of vascular endothelial growth factor (VEGF) and VEGFR2, thereby negatively modulating the activation of VEGFR2 and its downstream signalling pathways. Consistently, the pro-angiogenic effect of OGN KO was abrogated by VEGFR2 inhibition, supporting the critical role of VEGFR2 signalling in OGN-mediated regulation of angiogenic function. Conclusions OGN plays a critical role in negatively regulating ischaemia-induced angiogenesis by inhibiting VEGF–VEGFR2 signalling and thereby attenuating EC tube formation, proliferation, and migration. Thus, OGN may be a novel therapeutic target for ischaemic vascular diseases.