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Pulmonary arterial hypertension (PAH) is a progressive disease with a complex aetiology and high mortality. Functional and structural changes in the small pulmonary arteries lead to elevated pulmonary arterial pressure, resulting in right heart failure. The pathobiology of PAH is not fully understood, and novel treatment targets in PAH are desperately needed. The renin-angiotensin system is critical for maintaining homeostasis of the cardiovascular system. The system consists of the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang-(1–7)-Mas receptor axis. The former, the ACE-Ang II-AT1R axis, is involved in vasoconstrictive and hypertensive actions along with cardiac and vascular remodelling. The latter, the ACE2-Ang-(1–7)-Mas axis, generally mediates counterbalancing effects against those mediated by the ACE-Ang II-AT1R axis. Based on established functions, the ACE2-Ang-(1–7)-Mas axis may represent a novel target for the treatment of PAH. This review focuses on recent advances in pulmonary circulation science and the role of the ACE2-Ang-(1–7)-Mas axis in PAH.

The research aimed to study the effect of dexmedetomidine combined with bundle strategy on the cardiac function of patients with severe sepsis through pyramid speckle tracking algorithm-based echocardiography, expected to provide reference for its clinical treatment. 98 patients with severe sepsis or septic shock admitted to the hospital were selected as the research subjects, and they were equally divided into experimental group (dexmedetomidine + bundle strategy) and control group (dexmedetomidine + routine nursing), with 49 in each. Ultrasonic cardiogram examination was performed on patients before and after treatment, and the pyramid-based speckle tracking (PST) algorithm was designed and used. The results showed that the running time of the PST algorithm (105.25 s) was less than that of the BM algorithm (336.41 s), and the difference was statistically significant ( P < 0.05 ), and the systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the experimental group before treatment were not significantly different from those of the control group ( P > 0.05 ). The ultrasound index results found that the ejection fraction (EF) and fractional shortening (FS) of the two groups of patients showed a downward trend over time (1–7 days), while the E/A ratio showed an upward trend, and the E/A ratio of the experimental group was significantly greater than the control group ( P < 0.05 ). The systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the two groups of patients showed a downward trend over time (1–7 days), and the systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the experimental group were significantly lower than those of the control group ( P < 0.05 ). The 28-day mechanical ventilation time (6.97 ± 3.11 days), intensive care unit (ICU) stay time (9.18 ± 2.86 days), and the 28-day mortality rate (15.31%) of the experimental group were lower than those of the control group (6.97 ± 3.11 days; 13.08 ± 2.53 days; 31.95%) ( P < 0.05 ). In conclusion, the PST algorithm can effectively improve the quality of echocardiography and assist physicians in clinical evaluation, and dexmedetomidine combined with bundle strategy can stabilize the heart rate and reduce myocardial oxygen consumption in severe sepsis, while effectively shortens the recovery time and improves the overall prognosis.

Background. Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC. Methods. Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels. Results. A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls. Conclusion. Our immune-related signature panel may be a promising prognostic indicator for RC.

Attenuated vasodilatation of small arteries is a hallmark feature of hypertension. Salusin-β, which is a TOR2A gene product and an important vasoactive peptide, has a close relationship with cardiovascular disease. This study aimed to determinate the roles of salusin-β in vasodilatation, and its signal pathways in Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Isometric tension experiments were performed. Vasodilatation was induced by acetylcholine (ACh) or sodium nitroprusside (SNP). Plasma salusin-β levels and their protein expressions in coronary artery (CA), mesenteric artery (MA), and pulmonary artery (PA) of SHR were much higher than that of WKY. Intravenous injection of salusin-β increased arterial blood pressure in SHR, while anti-salusin-β IgG decreased it. Salusin-β further deteriorated, while anti-salusin-β IgG improved, the attenuated ACh-induced relaxation, the decreased nitric oxide (NO) level, and endothelial nitric oxide synthase (eNOS) activity in arteries of SHR, and salusin-β had no significant effect on SNP-induced relaxation. The NAD(P)H oxidase activity and reactive oxygen species (ROS) level in arteries of SHR were much higher than that of WKY, which was further increased by salusin-β but reduced by anti-salusin-β IgG. ROS scavenger NAC or antioxidant apocynin significantly inhibited, while SOD inhibitor DETC aggravated, the effects of salusin-β, and the eNOS inhibitor L-NAME inhibited the effects of anti-salusin-β IgG. These results indicated that enhanced salusin-β activity is involved in attenuated endothelium-dependent vasodilatation pathogenesis in SHR by activating NAD(P)H oxidase derived ROS generation and inhibiting eNOS activation and NO release.

Public key cryptographic (PKC) algorithms, such as the RSA, elliptic curve digital signature algorithm (ECDSA) etc., are widely used in the secure communication systems, such as OpenSSL, and a variety of information security systems. If designer do not securely implement them, the secret key will be easily extracted by side-channel attacks (SCAs) or combinational SCA thus mitigating the security of the entire communication system. Previous countermeasures of PKC implementations focused on the core part of the algorithms and ignored the modular inversion which is widely used in various PKC schemes. Many researchers believe that instead of straightforward implementation, constant time modular inversion (CTMI) is enough to resist the attack of simple power analysis combined with lattice analysis. However, we find that the CTMI security can be reduced to a hidden t-bit multiplier problem. Based on this feature, we firstly obtain Hamming weight of intermediate data through side-channel leakage. Then, we propose a heuristic algorithm to solve the problem by revealing the secret (partial and full) base of CTMI. Comparing previous necessary input message for masking filtering, our procedure need not any information about the secret base of the inversion. To our knowledge, this is the first time for evaluating the practical security of CTMI and experimental results show the fact that CTMI is not enough for high-level secure communication systems.

Background and aims Major vault protein (MVP) is up-regulated during infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Here, we found that MVP deficiency inhibited hepatocellular carcinoma (HCC) development induced by diethylnitrosamine, hepatitis B X protein, and HCV core. Approach and results Forced MVP expression was sufficient to induce HCC in mice. Mechanistic studies demonstrate that the ubiquitin ligase human double minute 2 (HDM2) forms mutual exclusive complexes either with interferon regulatory factor 2 (IRF2) or with p53. In the presence of MVP, HDM2 is liberated from IRF2, leading to the ubiquitination of the tumor suppressor p53. Mouse xenograft models showed that HBV and HCV promote carcinogenesis through MVP induction, resulting in a loss of p53 mediated by HDM2. Analyses of clinical samples from chronic hepatitis B, liver cirrhosis, and HCC revealed that MVP up-regulation correlates with several hallmarks of malignancy and associates with poor overall survival. Conclusions Taken together, through the sequestration of IRF2, MVP promotes an HDM2-dependent loss of p53 that promotes HCC development.

Activation of transient receptor potential vanilloid 4 (TRPV4) induces neuronal injury. TRPV4 activation enhances inflammatory response and promotes the proinflammatory cytokine release in various types of tissue and cells. Hyperneuroinflammation contributes to neuronal damage in epilepsy. Herein, we examined the contribution of neuroinflammation to TRPV4-induced neurotoxicity and its involvement in the inflammation and neuronal damage in pilocarpine model of temporal lobe epilepsy in mice. Icv. injection of TRPV4 agonist GSK1016790A (GSK1016790A-injected mice) increased ionized calcium binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) protein levels and Iba-1-positive (Iba-1

Nowadays, it is a growing need for energy shortage and environmental protection, and therefore the development of air conditioning and cooling system with ice slurry system has an important significance and broad application prospect. The ice-making using sub-cooling water has become one of the most stressed dynamic ice-making methods because of its simple structure, high heat transfer efficiency and high ice-making efficiency. However, the ice blockage occurs too frequently, resulting in a discontinuous ice-making and reducing the efficiency of the system. Aiming at dealing with the ice blockage, the experiment with the super-hydrophobic sub-cooler has been carried out, which provides theoretical and experimental basis for the optimum design of the ice-making system. It was found that a large sub-cooling degree and a long lasting time of sub-cooling state can be obtained with the super-hydrophobic sub-cooler, increasing the yield of ice slurry. As a result, the efficiency of the ice-making system is improved, achieving the purpose of energy saving.

Key points Chronic subcutaneous infusion of Ang II causes a progressive increase in blood pressure (BP) associated with significant increases in angiotensin type 1 receptor (AT1R) and mineralocorticoid receptor (MR) expression in hypothalamic nuclei. Intra-paraventricular nucleus (PVN) infusion of AAV- AT1aR-siRNA or of AAV-MR-siRNA markedly knockdown AT1a-R or MR expression in the PVN but not in the subfornical organ; or supraoptic nucleus, and prevent most of the increase in BP. These findings indicate that increased MR and AT1R activation in the PVN play a critical role in Ang II-induced hypertension in rats on regular salt intake. Abstract Circulating Ang II activates an aldosterone-mineralocorticoid receptor (MR) – angiotensin II (Ang II) – angiotensin type 1 receptor (AT1R) pathway in the hypothalamus. To obtain insights into the actual neuronal projections involved, adeno-associated virus carrying small interfering RNA against either AT1aR (AAV-AT1aR-siRNA) or MR (AAV-MR-siRNA) were infused into the paraventricular nucleus (PVN) in Wistar rats. Intra-PVN infusion of AAV-AT1aR-siRNA or AAV-MR-siRNA decreased AT1R or MR expression in the PVN but not in the subfornical organ (SFO) or supraoptic nucleus (SON). Subcutaneous infusion of Ang II at 500 ng kg−1 min−1 for 2 weeks increased mean arterial pressure by 60–70 mmHg, and increased AT1R and MR expression in the SFO, SON and PVN. Intra-PVN AT1aR-siRNA prevented the Ang II-induced increase in AT1R but not MR expression in the PVN, and MR-siRNA prevented MR but not AT1R expression in the PVN. The increases in AT1R and MR expression in both the SFO and the SON were not changed by the two AAV-siRNAs. Specific knockdown of AT1R or MR in the PVN by AAV-siRNA each prevented most of the Ang II-induced hypertension. Prevention of the subcutaneous Ang II-induced increase in MR but not the increase in AT1R by knockdown of MR and vice versa suggests an independent regulation of MR and AT1R expression in the PVN. Both AT1R and MR activation in the PVN play a critical role in Ang II-induced hypertension in rats.

Key points Central mineralocorticoid receptor (MR) and angiotensin II type 1 receptor (AT1R) activation play a critical role in sympathetic hyperactivity and progressive left ventricle (LV) remodelling and dysfunction after a myocardial infarction (MI). Intra-paraventricular nucleus (PVN) infusion of adeno-associated virus (AAV) carrying small interfering RNA (siRNA) against MR (AAV-MR-siRNA) markedly decreases both MR and AT1R expression in the PVN post MI, whereas AAV-AT1aR-siRNA only decreases AT1R expression. Both AAVs largely prevent sympathetic hyperactivity and inhibit part of LV remodelling and dysfunction post MI. These findings indicate that enhanced MR–AT1R signalling in the PVN is critical for sympathetic hyperactivity post MI, and contributes to part of LV dysfunction post MI. Abstract Intracerebroventricular infusion of a mineralocorticoid receptor (MR) or angiotensin II type 1 receptor (AT1R) blocker in rats attenuates sympathetic hyperactivity and progressive left ventricular (LV) dysfunction post myocardial infarction (MI). The present study examined whether knockdown of MRs or AT1Rs specifically in the paraventricular nucleus (PVN) contributes to these effects, and compared cardiac effects with those of systemic treatment with the β1-adrenergic receptor blocker metoprolol. The PVN of rats was infused with adeno-associated virus carrying small interfering RNA against either MR (AAV-MR-siRNA) or AT1R (AAV-AT1R-siRNA), or as control scrambled siRNA. At 4 weeks post MI, AT1R but not MR expression was increased in the PVN, excitatory renal sympathetic nerve activity and pressor responses to air stress were enhanced, and arterial baroreflex function was impaired; LV end-diastolic pressure (LVEDP) was increased and LV peak systolic pressure (LVPSP), ejection fraction (EF) and dP/dtmax decreased. AAV-MR-siRNA and AAV-AT1R-siRNA both normalized AT1R expression in the PVN, similarly ameliorated sympathetic and pressor responses to air stress, largely prevented baroreflex desensitization, and improved LVEDP, EF and dP/dtmax as well as cardiac interstitial (but not perivascular) fibrosis. In a second set of rats, metoprolol at 70 or 250 mg kg−1 day−1 in the drinking water for 4 weeks post MI did not improve LV function except for a decrease in LVEDP at the lower dose. These results suggest that in rats MR-dependent upregulation of AT1Rs in the PVN contributes to sympathetic hyperactivity, and LV dysfunction and remodelling post MI. In rats, normalizing MR–AT1R signalling in the PVN is a more effective strategy to improve LV dysfunction post MI than systemic β1 blockade.

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine. This double-blinded study aimed to investigate the efficacy and safety of a widely used traditional Chinese medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI) using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point was the American College of Rheumatology 20% improvement response criteria (ACR20). The secondary end point was that of adverse effect frequencies and the speed of onset action. Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment. After six months, ACR20 showed no significant difference among the three treatments. The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy 4.6 times faster. PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups. These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster, especially when patients need to relieve RA symptoms as soon as possible. Although not as effective as DMARDs, PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.

Central blockade of mineralocorticoid receptors (MRs) or angiotensin II type 1 receptors (AT1Rs) attenuates aldosterone (aldo)-salt induced hypertension. We examined the role of the subfornical organ (SFO), aldo synthesized locally in the brain, and MR and AT1R specifically in the paraventricular nucleus (PVN) in aldo-salt hypertension. Wistar rats were treated with subcutaneous aldo (1 μg/h) plus saline as drinking fluid, and gene expression was assessed by real-time qPCR. Other sets of rats received chronic intra-cerebroventricular (icv) infusion of aldo synthase (AS) inhibitor FAD286, MR blocker eplerenone or vehicle, electrolytic or sham lesions of the SFO, or intra-PVN infusion of AAV-MR-siRNA or AAV-AT1aR-siRNA. Infusion of aldo had no effect on 11βHSD2, MR and AT1R mRNA in different nuclei but increased CYP11B2 mRNA in the SFO, and serum and glucocorticoid-kinase 1 (Sgk1) and epithelial sodium channel (ENaC) γ subunit mRNA in the SFO and supraoptic nucleus (SON). MR-siRNA decreased both MR and AT1R mRNA in the PVN by ∼ 60%, but AT1aR-siRNA only decreased AT1R mRNA. SFO lesion, blockade of brain AS or MR, or knockdown of MR or AT1R in the PVN similarly attenuated aldosterone-induced saline intake by ∼ 50% and hypertension by ∼ 70%. These results suggest that an increase in circulating aldosterone may via MR and AT1R in the SFO increase local aldosterone production in hypothalamic nuclei such as the SON and PVN, and via MR enhance AT1R signaling in the PVN. This central aldosterone-MR-AT1R neuro-modulatory pathway appears to play a major role in the progressive hypertension.

Making friends based on the similarity of the profile of users is becoming common in many applications of mobile social networking. A major challenge for profile matching is to ensure the privacy of personal profiles which often contain highly sensitive information related to interests, political tendency, health conditions, and so on. The existing privacy preserving matchmaking protocols select the best match among people in the proximity based on the number of common attributes. This lucks detail information to find the best match such as in which attributes of the profile the user is currently interested most. On the other hand schemes that select best match based on the interest level of the user for the attributes assumes the attributes of the users are public which cannot be applied in applications that involve sensitive information about the user. Thus in this paper we propose privacy preserving match making protocol based on the user attributes in the profile and the dynamic interest level of the user for each attribute by applying homomorphic encryption techniques. The best match selected by the initiator have greater than a minimum number of attributes the initiator interested most currently in addition to relatively having a large number of common attributes. Non common attributes of the two matches remain private. Users other than the best matches can at most get the number of common attributes and whether the sum of common attributes interest level is above the threshold. The analysis shows that our protocol is efficient with the ability to resist the semi-honest and malicious adversary. And the simulation result shows that our proposed solution out performs the existing solution in energy overhead and execution time.

Topology control is a fundamental technique in Wireless Sensor Network (WSN), which forms the underlying topology for routing and other protocols by power control and neighbor selection. In recent years, various topology control algorithms with very different design goals have been proposed, and all of them try to form one optimized topology for all types of communications. Such solution makes a serious mistake by neglecting the fact that different communications have very different requirements. The most common communications in WSN are broadcast and data collection. For broadcast or message dissemination, the first priority is to spread the message throughout the network as quickly as possible. As for data collection, multi-factors should be taken into account, such as link length, hops to base station, node degree. With the very different goals, it is not possible to solve all those problems simultaneously with just one topology. In this paper, we propose a approach, which contains a Fast Dissemination Tree (FDT) and a Balanced Data Collection Tree (BDCT) to fulfill the requirements of the above two communications, i.e. message dissemination and data collection. And analysis and simulation proves that our method has a better performance when compared to the existed ones.

Environmental conservation issue advances the refrigerant substitute for the Freons. Natural working fluid must be a perfect choice. Therefore, natural friendly refrigerants R744 and R600a are selected in this research to be a binary mixture. Such a mixture can weaken their shortcomings by decreasing high heat rejection pressure as that of pure R744, and reducing flammability as that of pure R600a. Meanwhile the heating coefficient of performance (COP h ) increases. Theoretical thermal calculation of a refrigeration cycle using natural mixture R744/R600a has been conducted in this research. The results show that within the R744 mass fraction of 100/0∼94/6, the R744/R600a mixture can be charged directly. Under the same conditions, the optimum high pressure of R744/R600a system is reduced by 1.2MPa while the heating COPh is increased by 8.5%. Up to now, none of the potential substitutes can play a satisfying role in air conditioning and refrigeration fields. Research on R744/R600a refrigeration cycle is expected to offer useful guidelines for refrigerant substitute.