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Background Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) plays an important role in the formation of oxidative stress in brain tissues. We intended to investigate relationship between serum NOX4 concentrations and severity, delayed cerebral ischemia (DCI) plus prognosis after aneurysmal subarachnoid hemorrhage (aSAH). Methods Serum NOX4 concentrations were gauged in a total of 165 aSAH patients. The World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale were recorded for assessing hemorrhagic severity. Relations of serum NOX4 concentrations to DCI and 90-day poor outcome (Glasgow outcome scale score of 1–3) were determined using multivariate analysis. Results Serum NOX4 concentrations were substantially higher in patients with 90-day poor outcome or DCI than in other remainders. Serum NOX4 concentrations of patients were intimately correlated with WFNS scores and modified Fisher scores. Serum NOX4 appeared as an independent predictor for DCI and 90-day poor outcome after aSAH. Under ROC curve analysis, serum NOX4 concentrations possessed significantly high predictive capability for DCI and 90-day poor outcome following hemorrhagic stroke. Conclusions Serum NOX4 concentrations, in close correlation with hemorrhagic severity, were independently associated with DCI and poor clinical outcome after hemorrhagic stroke, substantializing serum NOX4 as a promising prognostic biomarker for aSAH.

The JinDeng Temple grottoes are large-scale grottoes that were dug in natural cliffs more than 500 years ago. The grotto art provides an important legacy and is of high historical, cultural, and artistic value. Over the course of more than 500 years, some areas of the grottoes have been seriously affected by seepage damage. Non-destructive detection methods (surface nuclear magnetic resonance and spontaneous potential) were used to investigate the cause of the seepage. The surface nuclear magnetic resonance method was successfully used to detect the spatial occurrence of groundwater and the water content per unit volume in the mountain above the grottoes. The results of spontaneous potential revealed the recharge and flow directions in the upper part of the mountain. The two methods used were complementary and provided mutually consistent results regarding the cause of water seepage in the grottoes, and the relationship between the positions of the water-bearing areas in the upper part of the mountain and the seepage. In addition, the two methods provided important basic data for the formulation of a work plan to protect and preserve the cultural relics.

The treatment for patients with poor-grade aneurysms defined as World Federation of Neurosurgical Societies (WFNS) grade IV-V is still unclear and controversial. In this research, we compared the clinical efficacy and safety between clipping and coiling in the treatment of ruptured poor-grade anterior circulation aneurysms.We conducted a retrospective analysis of a hospital database. From January 2013 to May 2018, 94 patients who presented with poor-grade anterior circulation aneurysms were included. Preoperative baseline, postprocedure complications, and outcome (3-month and 6-month modified Rankin Scale scores) were analyzed. Multivariate logistic regression analysis was conducted to identify risk factors of short-term (in-hospital, 30-day) mortality.A total of 21 (22%) patients died during short-term follow-up; there was a greater short-term mortality in coiling group (38% vs. 15%, P = 0.015). The incidence of delayed cerebral ischemia and intracranial infection in the clipping group was significantly greater than the coiling group: (33% vs. 14%, P = 0.045) and (68% vs. 41%, P = 0.016). However, coiling group had a greater rate of shunt-dependent hydrocephalus (21% vs. 6%, P = 0.035). Multivariate logistic regression analysis revealed cerebral vasospasm (odds ratio [OR], 9.22; P0.01), admission WFNS grade V (OR, 15.43; P0.01), coiling (OR, 5.92; P = 0.013), and postoperative aneurysm rebleeding (OR, 40.04; P = 0.01) would influence the mortality.Patients with ruptured poor-grade anterior circulation aneurysms who undergo microsurgical clipping seem to have a lower short-term mortality. Cerebral vasospasm, WFNS grade V, and postoperative aneurysm rebleeding are associated with short-term mortality.

Background Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. Methods Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. Results A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028). Conclusions Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

Background This meta-analysis aimed to evaluate the risk of shunt-dependent hydrocephalus among patients with ruptured intracranial aneurysms treated with either coil placement or clipping. Methods A systematic literature search of Embase, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using the STATA 12.0 software (Stata corporation, College Station, Texas, USA). Results Thirteen studies met all inclusion criteria and were included in the analysis. In total, these studies included 13,751 patients. Of the patients, 8444 of them underwent neurosurgical clipping, and 5307 underwent endovascular coiling. The overall result of a pooled estimate revealed there was no statistically significant risk of shunt dependency difference between the clipping and coiling groups (11.4% vs. 12.0%, respectively; relative risk [RR], 0.92; 95% confidence interval [CI], 0.84–1.01). Six prospective studies (n = 1373) reported shunt-dependent hydrocephalus revealed no significant difference between clipping and coiling (23.3% vs. 20.1%, respectively; RR, 1.12; 95% CI, 0.91–1.38). Seven retrospective studies (n = 12,378) reported shunt-dependent hydrocephalus found statistical significance between the surgical and endovascular treatment groups (10.0% vs. 11.1%, respectively; RR, 0.88; 95% CI, 0.79–0.98). Conclusions Microsurgical clipping and endovascular coiling of ruptured cerebral aneurysms are associated with similar incidences of ventricular shunt placement for hydrocephalus. The risk of shunt-dependent hydrocephalus is not higher after coiling than after clipping of ruptured intracranial aneurysms.

Thin cases and long treating time are shortcomings of conventional duplex treatment of aluminizing followed by nitriding (DTAN). Alternating current field (ACF) enhanced DTAN was carried out on AISI 1045 steel by applying an ACF to treated samples and treating agents with a pair of electrodes for overcoming those shortcomings. By investigating cases’ structures, phases, composition and hardness distributions of differently treated samples, preliminary studies were made on characterizations of the ACF enhanced duplex treatment to AISI 1045 steel. The results show that, with the help of the ACF, the surface Al-rich phase Al5Fe2 formed in conventional pack aluminizing can be easily avoided and the aluminizing process is dramatically promoted. The aluminizing case can be nitrided either with conventional pack nitriding or ACF enhanced pack nitriding. By applying ACF to pack nitriding, the diffusion of nitrogen into the aluminizing case is promoted. AlN, Fe2∼3N and solid solution of N in iron are efficiently formed as a result of reactions of N with the aluminizing case. A duplex treated case with an effective thickness of more than 170 μm can be obtained by the alternating current field enhanced 4 h pack aluminizing plus 4 h pack nitriding.

Allergic and related diseases have a substantial epidemiological impact on the pediatric population. Small molecule-based medicines have been traditionally used to manage the diseases. Omalizumab is the first monoclonal antibody-based medicine used in children's allergy and shows great promises. It binds to free IgE and prevents it from binding to IgE receptors, thus interrupting the IgE-dependent allergic inflammatory cascade. Vast amounts of data demonstrate its effectiveness and well tolerance by patients, including the children. However, the drug was only approved to use in allergic asthma and chronic spontaneous urticaria (CSU), though other applications were explored in clinical trials. In this review, we summarized current pediatric applications of omalizumab in allergic diseases, focusing on its usages beyond asthma and CSU, including allergic rhinitis, allergic bronchopulmonary aspergillosis, vernal keratoconjunctivitis, food allergy and atopic dermatitis. In addition, we highlighted the unmet needs and controversial issues of anti-IgE therapy., Highlights • Omalizumab, the first monoclonal antibody-based medicine used in children's allergy, shows great promise. • Omalizumab is effective in relieving symptoms associated with almost every children's allergic and related diseases beyond asthma and CSU. • There are unmet needs and controversial issues of anti-IgE therapy in allergic and related diseases.

Objective This study aimed to explore the mechanism of lncRNA MEG3 on angiogenesis after cerebral infarction (CI). Methods The rat brain microvascular endothelial cells (RBMVECs) isolated from rat was used to establish CI model, which were treated with oxygen-glucose deprivation/reoxygenation (OGD/R). The genes mRNA and protein expression levels in RBMVECs were determined by the quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively. The flow cytometry was used to measured cell apoptosis and intracellular reactive oxygen species (ROS) generation. The RBMVECs activities was detected by MTT method. The RNA-immunoprecipitation (RIP) assay was used to detect the interaction between MEG3 and p53, and the relationship between p53 and NOX4 was proved by chromatin co-immunoprecipitation (chip) assay. Results The results showed that OGD or OGD/R increased MEG3 and NOX4 expression, and there was positive correlation between MEG3 and NOX4 expression in RBMVECs. Next, knockdown of MEG3 indicated that inhibition of MEG3 was conducive to protect RBMVECs against OGD/R-induced apoptosis, with decreased NOX4 and p53 expression, further enhanced pro-angiogenic factors (HIF-1α and VEGF) expression, and reduced intracellular ROS generation. And then the RIP and CHIP assay demonstrated that MEG3 could interacted with p53 and regulated its expression, and p53 exerted significant binding in the promoters for NOX4, suggesting that MEG3 regulated NOX4 expression via p53. At last, knockdown of NOX4 indicated that inhibition of NOX4 protected RBMVECs against OGD/R-induced apoptosis, with increased cell viability and pro-angiogenic factors expression, and reduced ROS generation. Conclusion LncRNA MEG3 was an important regulator in OGD/R induced-RBMVECs apoptosis and the mechanism of MEG3 on angiogenesis after CI was reduced ROS by p53/NOX4 axis.

Because of its selective sensitivity to groundwater, surface nuclear magnetic resonance (SNMR) is a method widely applied in hydrogeology and engineering geology. However, the accurate numerical relationship between pulse moment intensity and exploration depth of this method has lacked research. Optimum pulse moment is a concept proposed to describe this correlation. By analyzing, using least-square fitting, various factors that may influence this correlation, an empirical relation for the optimum pulse moment has been obtained. The relation indicates a well-known law: to get a deeper exploration depth, a larger optimum pulse moment is needed. Moreover, from the relation, we found that the increase rate of exploration depth diminishes with the pulse moment increasing. Additionally, the correlation illustrates that the optimum exploration depth of the surface NMR method is not simply proportional to the loop diameter. Hence, to further extend the exploration depth, both the pulse moment intensity and the size of transmitter loop need to be increased simultaneously. Based on a synthetic example, we demonstrate that the optimum pulse sequence which is established from our empirical formula has a better inversion result and higher signal-to-noise ratio (SNR) when the probable depth range of the target aquifer is known.

Leitai is a cultural relic site consisting of a loess platform built during the Qianliang dynasty (1700 years ago), Han dynasty tombs (1800 years ago) built on the lower part of the loess platform, and the Leitai Taoist temple built on the upper part of the loess platform during the Ming dynasties (500 years ago). Thus, this site has considerable historical and cultural research value. Over hundreds of years, some cultural relics at this site have been destroyed. For instance, blue bricks from the Han dynasty have been crushed and compressed due to the subsidence of the sealing soil on top of the tombs and have moistened and weathered due to the high humidity in the tombs. Additionally, soil cracking has occurred on the east side of the loess platform. Existing geological data indicate that the observed damage may be related to increases in the water content of the silty loess soil in the inner part of the platform due to rainfall infiltration. Electrical resistivity tomography (ERT) and surface nuclear magnetic resonance (SNMR), which are nondestructive detection methods, were applied to further investigate the causes of the observed damage and identify areas where damage is occurring. These methods successfully reveal an area of silty soil with high moisture content due to rainfall infiltration. The moisture content at this soil site is close to or exceeds the plastic limit determined by soil sample testing; as a direct or indirect result, local cultural relics have been destroyed. From 3D visualizations of 2D ERT inversion resistivity data and slice diagrams, we further delineated the regional boundaries of areas that pose a threat to the security of the cultural relics at Leitai. These results may serve as an important reference for the development of cultural relic conservation programs.

Unruptured paraophthalmic aneurysms present unique challenges, and the ideal management remains unknown.We performed a pooled analysis of single-center experiences to compare the risks and effectiveness involving patients with unruptured paraophthalmic aneurysms treated with clipping, coiling alone, stent-assisted coiling, and flow-diversion. The MEDLINE database was searched and thirty-three series (including our institutional experience) were included.Clipping caused more intracranial hemorrhage (ICH) and neurologic complications (NCs) than coiling alone (ICH: odds ratio [OR] = 3.058, P = 0.013; NC: OR = 5.809, P0.001), stent-assisted coiling (ICH: P = 0.018; NC: OR = 7.367, P0.001), and flow-diversion (ICH: P = 0.006; NC: OR = 16.954, P0.001). Clipping also caused more unfavorable visual outcomes than both coiling alone (OR = 3.037, P = 0.001) and stent-assisted coiling (OR = 6.055, P = 0.005). Clipping resulted in a lower reoperation rate than coiling alone in large/giant aneurysm group, which approached statistical significance (OR = 0.133, P = 0.057). Clipping, stent-assisted coiling, and flow-diversion all showed higher occlusion rates compared with coiling alone (OR [clipping vs. coiling alone] = 2.852, P ≤ 0.001; OR [coiling alone vs. stent-assisted coiling] = 0.302, P = 0.003; OR [coiling alone vs. flow-diversion] = 0.400, P = 0.013). Flow-diversion showed comparative complication rate, clinical outcomes, and angiographic result compared with stent-assisted coiling. No significant differences were found among all 4 treatment modalities on mortality and poor outcome.Endovascular therapies have benefits over surgical clipping in terms of fewer intracranial hemorrhage complications, fewer NCs, and lower unfavorable visual outcome rate. Flow diversion showed comparative safety and effectiveness to stent-assisted coiling, and they both achieved better radiologic results than coiling alone. Further validation by randomized cohort studies is still needed to provide robust evidence.

Cross talk between phytohormones, nitric oxide (NO), and auxin has been implicated in the control of plant growth and development. Two recent reports indicate that NO promoted auxin signaling but inhibited auxin transport probably through S-nitrosylation. However, genetic evidence for the effect of S-nitrosylation on auxin physiology has been lacking. In this study, we used a genetic approach to understand the broader role of S-nitrosylation in auxin physiology in Arabidopsis. We compared auxin signaling and transport in Col-0 and gsnor1-3, a loss-of-function GSNOR1 mutant defective in protein de-nitrosylation. Our results showed that auxin signaling was impaired in the gsnor1-3 mutant as revealed by significantly reduced DR5-GUS/DR5-GFP accumulation and compromised degradation of AXR3NT-GUS, a useful reporter in interrogating auxin-mediated degradation of Aux/IAA by auxin receptors. In addition, polar auxin transport was compromised in gsnor1-3, which was correlated with universally reduced levels of PIN or GFP-PIN proteins in the roots of the mutant in a manner independent of transcription and 26S proteasome degradation. Our results suggest that S-nitrosylation and GSNOR1-mediated de-nitrosylation contribute to auxin physiology, and impaired auxin signaling and compromised auxin transport are responsible for the auxin-related morphological phenotypes displayed by the gsnor1-3 mutant.

Bcl-2 is one of the most important antiapoptotic members in mammals and prevents many forms of apoptosis in a variety of cell types. Our previous study revealed that overexpression of Bcl-2 significantly suppressed H2O2/NaCl-induced programmed cell death via inhibiting the transcriptional activation of OsVPE2 and OsVPE3 in transgenic rice. However, Ca(2+) and K(+) homeostasis of this process remains largely unknown. In the present study, we investigate whether nonselective cation channels (NSCC) blockers affect Bcl-2 function in rice under salt stress and how Bcl-2 affects ion homeostasis in salt stress-induced PCD. The results showed that overexpression of Bcl-2 significantly decreased transient elevations in the cytosolic Ca(2+) levels, inhibited NaCl-induced K(+) efflux but not H(+) efflux across the plasma membrane, and further suppressed the expression levels of OsVPE2 and OsVPE3, leading to the inhibition of salt-induced PCD and increase of tolerance to salt stress in transgenic rice. During the NaCl-induced PCD, the effects of a NSCC blocker La(3+) on ion homeostasis and VPEs expression in wild-type were similar to the effects of Bcl-2 overexpression in transgenic line. However, a synergistic effect of Bcl-2 and La(3+) was not obviously detectable. Our results suggested that Bcl-2 played an important role in suppression of NaCl-induced PCD by disruption of ion homeostasis, providing an insight into the mechanistic study of plant VPEs, cytosolic Ca(2+) level and K(+) efflux.

Direct current field (DCF) was employed in pack boriding at low and moderate temperatures. Samples were arranged in different positions in a sealed pack boriding container for studying characteristics of the DCF assisted pack boriding and mechanisms of accelerating pack boriding by DCF. The test results revealed that DCF enhanced pack boriding not only to samples as cathode but also to samples located between the cathode and anode. The extent of the enhancement varied with the location of the sample. The strongest enhancement was achieved on the cathode sample's side facing the anode. It is proposed that the DCF's physical effect of enhancing chemical reactions in the agent increases the activity and productivity of boron-containing species. The DCF makes the concentrations of active boron-containing species at and around the sample as cathode much higher than in any other position by forcing boron-containing species to diffuse fast toward the cathode. The electrically induced boron migration in the sample by DCF leads a faster growth of boriding case at the sample's side facing the anode. The DCF's electromagnetic effect might be helpful for forming more vacancies in the sample, which favors boron's diffusion in the substrate.

This paper focuses on the interstory drift ratio (IDR) demands of building structures subjected to near-fault ground motions having different impulsive characteristics based on generalized interstory drift spectral analysis. The near-fault ground motions considered include the idealized simple pulses and three groups of near-fault ground motions with forward directivity pulses, fling-step pulses and without velocity pulse. Meanwhile, the building systems are equivalently taken as shear-flexural beams with representative lateral stiffness ratios. The IDR distribution of continuous beams subjected to three groups of near-fault ground motions is acquired. It is illustrated that the maximum IDR shifts from the upper half to the lower half of buildings with an increase in lateral stiffness ratio. For long-period systems, the average IDR under impulsive ground motions is significantly greater than that under non-pulse motions. Finally, for moment-resisting frame buildings the forward directivity pulses amplify the drift response of higher modes, while the fling-step pulses excite primarily their contribution in the first mode and generate large deformation in the lower stories. The essential reason for this phenomenon is revealed according to the distinct property of near-fault impulsive ground motions and generalized drift spectral analysis.

Our previous data showed that apoptotic suppressors inhibit aluminum (Al)-induced programmed cell death (PCD) and promote Al tolerance in yeast cells, however, very little is known about the underlying mechanisms, especially in plants. Here, we show that the Caenorhabditis elegans apoptotic suppressor Ced-9, a Bcl-2 homologue, inhibited both the Al-induced PCD and Al-induced activity of caspase-like vacuolar processing enzyme (VPE), a crucial executioner of PCD, in tobacco. Furthermore, we show that Ced-9 significantly alleviated Al inhibition of root elongation, decreased Al accumulation in the root tip and greatly inhibited Al-induced gene expression in early response to Al, leading to enhancing the tolerance of tobacco plants to Al toxicity. Our data suggest that Ced-9 promotes Al tolerance in plants via inhibition of Al-induced PCD, indicating that conserved negative regulators of PCD are involved in integrated regulation of cell survival and Al-induced PCD by an unidentified mechanism.

Growth hormone is one of the most important hormones, which is involved in many reproductive processes of giant panda Ailuropoda melanoleuca. In this study, the mature peptide of A. melanoleuca growth hormone (AmGH) was successfully expressed and secreted in Pichia pastoris under the control of AOX1 promoter. The expression condition for AmGH in P. pastoris, such as the expression time, pH value and methanol concentration in the BMMY were optimized and the AmGH expression level is about 100 mg/L using GS115 recombinant under optimized condition (96 h of 1.5% methanol induction). The secreted nascent AmGH were purified using ammonium sulfate fractionation. The mature AmGH protein exhibited a molecular mass of approximately 22 kDa on SDS–PAGE. This study would provide a new opportunity for large-scale expression and purification of AmGH, which might facilitate studies on the biological activity of AmGH.

Ultraweak luminescence (UL) changes and sister-chromatid exchanges (SCEs) induced by Al toxicity were investigated in root tip cells of barley (Hordeum vulgare L.). A low positive correlation between relative UL rates and root relative elongation rates (RERs) was observed in 30 barley cultivars. During 1.5–24 h exposure to 20 μM Al solution, the UL value in cv Humai 16 (Al-tolerant) was higher than that in cv 2000-2 (Al-sensitive), suggesting that UL is a possible mechanism by which Al-tolerant cultivars avoid reactive oxygen species (ROS) toxicity. Upon raising Al levels (>50 μM), the increase for UL in Al-tolerant and sensitive cultivars possibly involved cell death. A significant increase in the SCE rate was observed in cv 2000-2 but not in cv Humai 16 at 20 μM Al level, suggesting that mechanisms of Al-tolerance might block the occurrence of Al-induced SCEs. With raising Al levels (0–640 μM), SCE rates first increased and then decreased in the two cultivars, but their Al levels inducing the highest SCE rate were 10 μM in cv 2000-2 and 320 μM in cv Humai 16. In cv 2000-2, SCEs reached saturation status after 4 h treatment with 10 μM Al, suggesting that SCEs can be considered as a sensitive indicator for Al phytotoxicity. Ascorbic acid (ASA) pretreatment could significantly inhibit Al-induced SCE occurrence, indicating that Al indirectly induces SCEs via Al-triggered ROS formation. To our knowledge, this is the first report demonstrating that Al can induce UL changes and SCEs in root tip cells, and that may serve as possible indicators and thereby provide new insights into the mechanisms of Al toxicity and tolerance in barley.