Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We ...perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.
Nano-hydroxyapatite and its composites(nHA) have been widely used as grafts in inter-vertebral fusion. However, the safety and efficacy of the graft in inter-vertebral fusion is controversial. This ...meta-analysis aimed at evaluating the safety and efficacy of nHA and non-hydroxyapatite grafts (noHA) (autologous bone, etc.) in inter-body fusion.
A comprehensive search was performed in electronic database as follows: PubMed, EMBASE, the Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI) from inception until October 2022. Clinical studies on the effect of nHA and noHA in spinal fusion were collected. Analysis of outcome indicators using RevMan 5.4 statistical software.
The meta-analysis showed that the operation time of patients who underwent inter-body fusion with nHA grafts was less than that of patients who underwent noHA (p < 0.05). Compared with the noHA group, the nHA group can achieve similar clinical effects in the fusion rate(OR = 1.29,95%CI: 0.88 to 1.88,p = 0.19),Subsidence rate(OR = 1.2,95%CI:0.44 to 3.28,p = 0.72), inter-vertebral space height(SMD = 0.04,95%CI:-0.08 to 0.15,p = 0.54),Cobb angle(SMD = 0.21,95%CI: 0.18 to 0.6,p = 0.21),Blood loss(SMD = -36.58,95%CI: -81.45 to 8.29,p = 0.11),operative time in 12 months(SMD = -5.82,95%CI: -9.98 to -1.67,p = 0.006) and in the final follow-up(SMD = -0.38,95%CI: -0.51 to -0.26,p < 0.00001),ODI(SMD = 0.68,95%CI: -0.84 to 2.19,p = 0.38), VAS(SMD = 0.17,95%CI: -0.13 to 0.48,p = 0.27) and adverse events(OR = 0.98,95%CI: 0.66 to 1.45,p = 0.92), and the differences are not statistically significant.
This meta-analysis suggests that nHA matrix grafts are similar to noHA grafts in the safety and efficacy of spinal reconstruction, and are an ideal material for inter-vertebral bone grafting.
To investigate risk factors of bone cement leakage in percutaneous vertebroplasty(PVP)for osteoporotic vertebral compression fracture (OVCF).
A total of 236 patients (344 vertebrae) who underwent PVP ...between November 2016 and June 2020 were enrolled in the study. Clinical and radiological characteristics, including age, gender, course of disease, trauma, type of vertebral fracture, cortical continuity of vertebral body, intervertebral vacuum cleft (IVC), fracture severity, fracture level, basivertebral foramen, bone cement dispersion types, the cement injection volume, the type of cement leakage, puncture approach, and intrusion of the posterior wall, were considered as potential risk factors. Three types of leakage (type-B, type-C, and type-S) were defined and risk factors for each type were analyzed. Logistic analysis was used to study the relationship between each factor and the type of cement leakage.
The incidences of the three types of leakage were 28.5%, 24.4%, and 34.3%. The multinomial logistic analysis revealed that the factors of type-B leakage were the shape of cement and basivertebral foramen. One significant factor related to type-C leakage was cortical disruption, and the factors of type-S leakage were bone cement dispersion types, basivertebral foramen, cleft, fracture severity, an intrusion of the posterior wall, and gender.
Different types of cement leakage have their own risk factors, and the analysis of risk factors of these might be helpful in reducing the rate of cement leakage.
Purpose
Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to ...acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging.
Materials and Methods
Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density‐weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross‐sectional and longitudinal distribution of BA plaque were analyzed with a custom‐developed tool.
Results
In all, 85 BA plaques were detected in 61 recruited patients. For cross‐sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%).
Conclusion
Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592–1599.
Patients with diabetes mellitus (DM) have an increased risk of diabetic encephalopathy symptoms such as depressive-like behaviour and cognitive impairment. Exercise is an effective strategy for ...preventing and treating DM and diabetic complications. The aim of this study is to investigate the effects and potential mechanisms of treadmill exercise training on diabetes-induced depressive-like behavior and cognitive impairment in db/db mice. In this study, the mice were divided into three groups (n = 10 per group) as follows: healthy-sedentary (db/m), diabetes-sedentary (db/db), and diabetes-treadmill exercise training (db/db-TET). The db/db-TET mice were performed five days per week at a speed of 8 m/min for 60 min/day for 8 weeks, following which body weight, fasting blood glucose, insulin resistance, behavioral, synaptic ultrastructure, oxidative stress, apoptotic signaling, and inflammatory responses were evaluated. As a result, treadmill exercise training significantly decreased body weight and fasting blood glucose levels, increased insulin sensitivity, protected synaptic ultrastructure, reduced depression-like behavior, and improved learning and memory deficits in db/db mice. In addition, treadmill exercise training significantly suppressed NOX2-mediated oxidative stress, resulting in a decrease in NOX2-dependent ROS generation in the db/db mouse hippocampus CA1 region. Reduced ROS generation prevented the apoptotic signaling pathway and NLRP3 inflammasome activation, thereby ameliorating hippocampus neuronal damage. In summary, the results indicated that treadmill exercise training significantly ameliorates hippocampus injury by suppressing oxidative stress-induced apoptosis and NLRP3 inflammasome activation, consequently ameliorating diabetes-induced depressive-like behavior and cognitive impairment in db/db mice.
•Exercise alleviates depressive-like and cognitive impairment in db/db mice.•Exercise increases levels of functional synaptic proteins (PSD95 and synapsin).•ROS over-generation activates apoptosis and NLRP3 inflammasome.•Exercise suppresses NOX2 expression and subsequently inhibits ROS over-production.
Osteoarthritis (OA) is a chronic debilitating disease characterized by joint degeneration. Excessive chondrocyte apoptosis and inflammation contributes to articular cartilage destruction in OA ...pathology. Nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) has emerged as a critical regulator of inflammation that participates in the pathology of diverse diseases. To date, little is known about the role of NLRX1 in OA. In the present study, we aimed to explore the function of NLRX1 in lipopolysaccharide (LPS)-induced injury in chondrocytes, an in vitro model of OA. NLRX1 mRNA was detected by quantitative polymerase chain reaction (qPCR) analysis. Protein expression of NLRX1, phosphorylated IκB kinase β (IKKβ), and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by western blot. Cell viability was assessed by the MTT assay. Cell apoptosis was evaluated by measuring caspase-3 activity. Cytokine release was assessed by enzyme-linked immunosorbent assay (ELISA). NF-κB signaling activation was analyzed with a luciferase reporter assay. Herein, our results revealed that NLRX1 expression was markedly decreased in LPS-treated chondrocytes. Functional experiments demonstrated that NLRX1 overexpression significantly improved cell viability and attenuated LPS-treated chondrocyte apoptosis and inflammation, while NLRX1 silencing caused the opposite effects. Moreover, our results showed that NLRX1 regulated LPS-induced NF-κB signaling activation. Notably, NF-κB signaling inhibition significantly reversed the NLRX1-knockdown-mediated enhanced effects on LPS-induced apoptosis and inflammation. Overall, these results demonstrate that NLRX1 alleviates LPS-induced apoptosis and inflammation in chondrocytes by negatively regulating NF-κB signaling, results that indicate an anti-inflammatory role for NLRX1 in OA. Our findings suggest that NLRX1 may serve as a potential therapeutic target for OA.
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•NLRX1 is decreased by LPS in chondrocytes.•NLRX1 overexpression reduces LPS-induced injury in chondrocytes.•NLRX1 inhibits LPS-induced activation of NF-κB signaling.•NF-κB inhibition reverses the NLRX1-inhibition-mediated effect.
To investigate the impact of interfacial layer effects on the thermal conductivity of nanofluids and the microscopic mechanisms of enhanced thermal conductivity, this study employed non-equilibrium ...molecular dynamics to compute the thermal conductivity, number density, radial distribution function, and mean square displacement distribution of SiC nanofluids. The impact of nanoparticle volume fraction and particle size parameters on the thermal conductivity of nanofluids and the structure of interfacial adsorption layers was discussed. The simulation calculation results show that the coefficient of thermal conductivity of nanofluid is positively related to the volume fraction of nanoparticles, increasing from 0.6529 W/(m·K) to 0.8159 W/(m·K), and the enhancement of thermal conductivity by the volume fraction can be up to 33.97 %. The thermal conductivity is inversely correlated with the change in particle size, and the maximum improvement in thermal conductivity by particle size can reach up to 12.05 %. The simulated results of the thermal conductivity of nanofluid are almost consistent with the predicted results of the Yu&Choi model, and the error is controlled within 5 %. Simultaneously, the thickness of the interfacial adsorption layer decreases with an increase in particle size. This reduction arises due to larger particles having a smaller specific surface area, resulting in fewer particle surfaces covered by the interface layer. Moreover, the impact of particle size on the arrangement and affinity of molecules within the interface layer contributes to this decrease. Overall, interface layer effects exhibit a dual impact on the thermal conduction of nanofluids. The structured formation and high-density distribution of the adsorption layer contribute to enhanced heat transfer, while thermal resistance between nanoparticle surfaces and the fluid restricts heat transmission.
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, with few therapeutic options available to slow its progression. Aerobic exercise training is an effective strategy for ...diabetes mellitus and its complications' prevention and treatment. The purpose of this study was to determine the effects of aerobic exercise training on diabetic kidney injury in db/db mice and to characterize the mechanism underlying the renal protective effects. The db/db mice were exercised 5 days a week for 60 min each day for 8 weeks at a speed of 5.6 m/min, after which renal function, morphology, oxidative stress, inflammation, fibrosis, and the expression of the Nox4/ROS/NF-κB/NLRP3 signaling pathway-related protein were assessed. Our results showed that aerobic exercise training significantly reduced body weight and microalbuminuria, improved renal function, and attenuated renal pathological changes in db/db mice independent of hyperglycemic state. Aerobic exercise training was also found to significantly improve oxidative stress and inflammation in the kidneys of db/db mice by decreasing the activity of complex I, the levels of MDA, 8-OHdG, Nox4, ROS, TNF-α, MCP-1, IL-6, and IL-18, increasing the activities of SOD and GSH-Px, the expression of klotho and NPHS2, and decreasing the phosphorylation of NF-κB p65 and IκBα, as well as the expression of NLRP3, ASC, caspase-1 p20, and IL-1β. Additionally, aerobic exercise training decreased TGF-β, collagen I, collagen IV, and α-SMA expression, thereby slowing the progression of kidney fibrosis in db/db mice. In conclusion, aerobic exercise training effectively reduces oxidative stress, inflammation, and renal fibrosis by modulating the Nox4/ROS/NF-κB/NLRP3 signaling pathway, implying that aerobic exercise training has significant potential to protect diabetic kidney injury and should be given more emphasis in DKD treatment.
•Exercise alleviates high glucose-induced renal injury in db/db mice.•Exercise improves glomerular ultrastructure in db/db mice.•Exercise suppresses Nox4 expression and subsequently inhibits ROS over-production.•ROS over-generation activates NLRP3 inflammasome.
Event detection have long been a fundamental problem in computer vision society. Various datasets for recognizing human events and activities have been proposed to help developing better models and ...methods, such as UCF101, HMDB51, etc. These datasets all share the same properties that either predefined scripts are provided or the images are almost actor-oriented with little background noise. These properties, however, are completely different from that of surveillance event detection, making the effective solutions on these datasets totally not suitable. Event detection in complex surveillance video is a much more difficult task with several challenges: heavy occlusions between pedestrians, low image resolution and uncontrolled scene condition. TRECVID-SED evaluation, aiming at detecting events in highly crowded airport, is well-known for its great difficulties. To deal with event detection in realistic scene, such as TRECVID-SED, we introduce a comprehensive solution framework based on pedestrian detection, deep key-pose detection and trajectory analysis. Explicitly, instead of detecting whole body of one person, we detect the head-shoulder of pedestrian, addressing the issue of heavy occlusion of pedestrians in complex scene. We also propose a trajectory-based event detection method so as to better focus on the key actors of events. For those events with discriminative poses, we model the event detection as key pose detection by taking advantages of Faster R-CNN. The presented framework achieves the best result in TRECVID-SED 2016 evaluation.
Aims
Chronic hyperglycemia‐induced inflammation of the hippocampus is an important cause of cognitive deficits in diabetic patients. The receptor for advanced glycation end products (RAGE), which is ...widely expressed in the hippocampus, is a crucial factor in this inflammation and the associated cognitive deficits. We aimed to reveal the underlying mechanism by which RAGE regulates neuroinflammation in the pathogenesis of diabetes‐induced cognitive impairment.
Methods
We used db/db mice as a model for type 2 diabetes to investigate whether receptor‐interacting serine/threonine protein kinase 1 (RIPK1), which is expressed in microglia in the hippocampal region, is a key protein partner for RAGE. GST pull‐down assays and AutoDock Vina simulations were performed to identify the key structural domain in RAGE that binds to RIPK1. Western blotting, co‐immunoprecipitation (Co‐IP), and immunofluorescence (IF) were used to detect the levels of key proteins or interaction between RAGE and RIPK1. Cognitive deficits in the mice were assessed with the Morris water maze (MWM) and new object recognition (NOR) and fear‐conditioning tests.
Results
RAGE binds directly to RIPK1 via the amino acid sequence (AAs) 362–367, thereby upregulating phosphorylation of RIPK1, which results in activation of the NLRP3 inflammasome in microglia and ultimately leads to cognitive impairments in db/db mice. We mutated RAGE AAs 362–367 to reverse neuroinflammation in the hippocampus and improve cognitive function, suggesting that RAGE AAs 362–367 is a key structural domain that binds directly to RIPK1. These results also indicate that hyperglycemia‐induced inflammation in the hippocampus is dependent on direct binding of RAGE and RIPK1.
Conclusion
Direct interaction of RAGE and RIPK1 via AAs 362–367 is an important mechanism for enhanced neuroinflammation in the hyperglycemic environment and is a key node in the development of cognitive deficits in diabetes.
Proposed mechanism underlying RAGE regulation of cognitive deficits. Direct binding of RAGE AAs 362–367 to RIPK1 is responsible for activation of RIPK1 and the NLRP3 inflammasome, leading to subsequent cognitive deficits.
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