Abstract Background To investigate whether remote ischemic conditioning (RIC) can attenuate ischemic reperfusion injury (IRI) in recipients after kidney transplantation using donation after cardiac ...death. Methods Forty-eight recipients referred for kidney transplantation were recruited. The paired recipients who received the kidneys from the same donor were randomly assigned (one received RIC and the other did not). RIC was induced by three 5-min cycles of brief repetitive ischemia and reperfusion by clamping the exposed external iliac artery. Blood samples were withdrawn at hour 2, hour 12, days 1–7, day 14, and day 30 to measure serum creatinine level and estimated glomerular filtration rate after transplantation. Urine samples were collected at hours 2, 12, 24, and 48 to measure urine neutrophil gelatinase–associated lipocalin after transplantation. Renal tissues were obtained at 30 min for histologic changes after transplantation. Results There were no significant differences in clinical characteristics of the recipients and donors between RIC and control groups. The serum creatinine level was lower in the RIC group compared with that of the control group (12 h, days 1–14, P < 0.05; other P > 0.05); the estimated glomerular filtration rate was higher in the RIC group compared with that of the control group (12 h, days 1–14, P < 0.05; other P > 0.05); urine neutrophil gelatinase–associated lipocalin, an early marker of IRI, was lower in the RIC group at hours 2, 12, 24, and 48 (2 h, 48 h, P > 0.05; 12 h, 24 h, P < 0.05) compared with that of the control group. The graft pathology showed no differences between RIC and control groups. Conclusions RIC enhanced the early recovery of renal function in recipients after kidney transplantation. Our results provide a novel potential approach to attenuate transplantation-associated IRI.
Summary Background The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016–17 prompted concerns that the epidemiology of the virus might ...have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016–17 epidemic compared with previous epidemics. Methods In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques. Findings Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013–14, 219 in 2014–15, 114 in 2015–16, and 447 in 2016–17. The 2016–17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016–17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015–16 and 2016–17 epidemics (63% 72 of 114 and 61% 274 of 447, respectively) were higher than those in the first three epidemics (39% 52 of 134, 55% 169 of 306, and 56% 122 of 219, respectively). The clinical severity of individuals admitted to hospital in the 2016–17 epidemic was similar to that in the previous epidemics. Interpretation Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus. Funding The National Science Fund for Distinguished Young Scholars.
Abstract Recent studies show that designer peptide nanofibers can mimic properties of extracellular matrix molecules, promising great potential as scaffold materials for tissue engineering. However, ...their ability in supporting organogenesis has not been studied. Here we examined the effect of self-assembling peptide hydrogels in supporting skin derived precursors (SKPs) in hair follicle neogenesis. We found that hydrogels formed by RADA16, PRG which contains RGD, and particularly the combination of RADA16 and PRG (RADA-PRG) enhanced SKP proliferation. Notably, the RADA-PRG hydrogel, which exhibited advantages of RADA16 in adequate nanofiber formation and PRG in providing the integrin binding sequence, exhibited superior effects in enhancing SKP survival, expression of hair induction signature genes such as Akp2 and Bmp6 , and more importantly de novo hair genesis in mice. Thus our results suggest that RADA-PRG may serve as a novel scaffold material for stem cell transplantation and tissue engineering.
Background and Purpose
Inactivation of the gene for adenosine A2A receptors (ADORA2A for humans and Adora2a for rodents) protects against brain injury in experimental stroke. However, the ...cell‐specific pathogenic effects of A2A receptors in thromboembolic stroke and the underlying mechanisms remain undefined. Here, we tested the hypothesis that inhibition of endothelial A2A receptors after thromboembolic stroke improves post‐stroke outcomes via down‐regulation of inflammation.
Experimental Approach
Thromboembolic stroke was induced by embolic middle cerebral artery occlusion in mice. Post‐stroke outcomes were determined with neurological deficit scoring, infarct volume, inflammatory marker expression, brain leukocyte infiltration, blood–brain barrier (BBB) leakage, and oedema assessment. Anti‐inflammatory effects of silencing the gene for A2A receptors or pharmacological antagonism of these receptors were assessed in vitro.
Key Results
Thromboembolic stroke induced Adora2a expression in the brain. Mice globally deficient in Adora2a (Adora2a−/−) were resistant to stroke injury. Mice specifically deficient in endothelial Adora2a (Adora2aΔVEC) showed reduced leukocyte infiltration, BBB leakage, and oedema after stroke, along with attenuated downstream proinflammatory markers, both in vivo and in vitro. The A2A receptor antagonist, KW 6002, also reduced brain injury and inflammation after stroke. Inactivation of ADORA2A inhibited endothelial inflammation via suppression of the NLRP3 inflammasome, down‐regulating cleaved caspase 1 and IL‐1β expression.
Conclusions and Implications
Specific inactivation of endothelial A2A receptors mitigated ischaemic brain injury and improved post‐stroke outcomes, at least partly, through anti‐inflammatory effects via blockade of NLRP3 inflammasome activity. Our findings may open new approaches to vascular protection after ischaemic stroke.
In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate ...the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality.
We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022.
We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO.
Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model.
Fifty-four studies (
= 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (
= 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO.
COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.
With the modern semiconductor supply chain, the ownership of both intellectual property (IP) and integrated circuit (IC) cannot be guaranteed. The IP piracy may take place at the untrusted IC ...designer or untrusted foundry without the knowledge of the original IP owner. The untrusted foundry can also perform IC piracy with reverse engineering of GDSII, overproducing the number of ICs, and shipping out-of-spec/defective devices. A holistic solution is proposed to protect the ownership of both IP owners and IC designers. In this solution, a dynamically obfuscated wrapper for split test (DOST) and a secure split test methodology together aim at preventing IP overusing at multiple abstraction levels and enabling IC designers to fully control the production, test, and authentication processes. DOST has been implemented and validated on video graphics array-liquid crystal display, floating-point and graphics unit, Leon3, and Leon3mp benchmarks. DOST enables the structural tests in the locked mode and the functional tests in the functionally unlocked mode. The results show that the proposed method is highly robust against IP and IC piracies with an insignificant area (1.381%) and power (1.276%) overhead.
Insecticide overuse in crop production systems often results in detrimental effects on predators and parasitoids, which regulate important insect pests. The natural enemies are also unable to survive ...in monocrop landscapes with the absence of shelter or food sources. Diversified vegetation, especially with flowering plants, can enhance natural enemy abundance and diversity, thus strengthening biological control, enabling farmers to reduce insecticides. In this study, we conserved bund vegetation and manipulated the existing rice landscapes with flowering plants to provide food and shelter for the biological control agents. Our study revealed significant positive relationships between predator densities and bund plant diversity. The abundance of predators significantly increased in the eco-engineered plots, especially at the flowering peaks compared to the insecticide-treated and control plots, while parasitoids were more diverse in both the eco-engineered and control plots. There were no significant differences in planthopper and leafhopper densities among the treatments during the rice early and maximum tillering stages, suggesting effective natural control of these herbivore pests in the eco-engineered plots at the early rice-growing season. However, at the heading stage relatively higher planthopper and leafhopper populations in the control and eco-engineered plots than in the insecticide-sprayed plots were recorded, suggesting perhaps the need for insecticide interventions if exceeding the threshold at this time. Our study indicates that manipulating the habitats surrounding the rice fields to enhance natural enemies is a sustainable practice in rice production as it can enhance the natural suppression of pests and thus reducing the need for insecticide.
Inactivation of the gene for adenosine A
receptors (ADORA2A for humans and Adora2a for rodents) protects against brain injury in experimental stroke. However, the cell-specific pathogenic effects of ...A
receptors in thromboembolic stroke and the underlying mechanisms remain undefined. Here, we tested the hypothesis that inhibition of endothelial A
receptors after thromboembolic stroke improves post-stroke outcomes via down-regulation of inflammation.
Thromboembolic stroke was induced by embolic middle cerebral artery occlusion in mice. Post-stroke outcomes were determined with neurological deficit scoring, infarct volume, inflammatory marker expression, brain leukocyte infiltration, blood-brain barrier (BBB) leakage, and oedema assessment. Anti-inflammatory effects of silencing the gene for A
receptors or pharmacological antagonism of these receptors were assessed in vitro.
Thromboembolic stroke induced Adora2a expression in the brain. Mice globally deficient in Adora2a (Adora2a
) were resistant to stroke injury. Mice specifically deficient in endothelial Adora2a (Adora2a
) showed reduced leukocyte infiltration, BBB leakage, and oedema after stroke, along with attenuated downstream proinflammatory markers, both in vivo and in vitro. The A
receptor antagonist, KW 6002, also reduced brain injury and inflammation after stroke. Inactivation of ADORA2A inhibited endothelial inflammation via suppression of the NLRP3 inflammasome, down-regulating cleaved caspase 1 and IL-1β expression.
Specific inactivation of endothelial A
receptors mitigated ischaemic brain injury and improved post-stroke outcomes, at least partly, through anti-inflammatory effects via blockade of NLRP3 inflammasome activity. Our findings may open new approaches to vascular protection after ischaemic stroke.
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