Neutrophil extracellular traps mediate neuro-immunothrombosis

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

Compact magneto-optical traps using planar optics

Magneto-optical traps (MOTs) composed of magnetic fields and light fields have been widely utilized to cool andconfine microscopic particles. Practical technology applications require miniaturized MOTs. The advancement of planaroptics has promoted the development of compact MOTs. In this article, we review the development of compact MOTs basedon planar optics. First, we introduce the standardMOTs. We then introduce the gratingMOTs with micron structures, whichhave been used to build cold atomic clocks, cold atomic interferometers, and ultra-cold sources. Further, we introducethe integrated MOTs based on nano-scale metasurfaces. These new compact MOTs greatly reduce volume and powerconsumption, and provide new opportunities for fundamental research and practical applications.

Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway

Objective The hypersensitivity of the kidney makes it susceptible to hypoxia injury.The involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been reported.In this study,we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism.Methods A total of 24 SD male rats were divided into three groups(n=8 each):normal control group,hypoxia group and hypoxia+pyrrolidine dithiocarbamate(PDTC)group.Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters(oxygen partial pressure about 6.9 kPa)for 7 days.PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days.Pathological changes of the rat renal tissues were observed under a light microscope;the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cell-free DNA(cf-DNA)and reactive oxygen species(ROS)were measured;the expression levels of myeloperoxidase(MPO),citrullinated histone H3(cit-H3),B-cell lymphoma 2(Bcl-2),Bax,nuclear factor kappa B(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in rat renal tissues were detected by qRT-qPCR and Western blotting;the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining.Results After hypoxia,the expression of NF-κB protein in renal tissues was significantly increased,the levels of SCr,BUN,cf-DNA and ROS in serum were significantly increased,the formation of NETs in renal tissues was significantly increased,and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues.When PDTC was used to inhibit NF-κB activation,NETs formation in renal tissue was significantly decreased,the expression level of Bcl-2 in renal tissues was significantly increased,the expression level of Bax was significantly decreased,and renal injury was significantly alleviated.Conclusion HH induces the formation of NETs through the NF-κB signaling pathway,and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

Blood neutrophil extracellular traps:a novel target for the assessment of mammary health in transition dairy cows

Background:Mammary health is important for transition dairy cows and has been well recognized to exert decisive effects on animal welfare.However,the factors influencing mammary health are still unclear.Differential somatic cell count(DSCC)could reflect the mastitis risk since it is the percentage of neutrophils plus lymphocytes in total somatic cells and could be reflective of mammary health of dairy cows.This work aimed to investigate the assessment and prognosis of the health of transition cows based on blood neutrophil extracellular traps(NETs).Results:Eighty-four transition Holstein dairy cows were selected.The serum was sampled in all the animals at week 1 pre-and postpartum,and milk was sampled at week 1 postpartum.Based on the DSCC in milk at week 1,cows with lower(7.4%±4.07%,n=15)and higher(83.3%±1.21%,n=15)DSCCs were selected.High DSCC cows had higher levels of red blood cell counts(P<0.05),hemoglobin(P=0.07),and hematocrit(P=0.05),higher concentrations of serum oxidative variables[reactive oxygen species(P<0.05),malondialdehyde(P<0.05),protein carbonyl(P<0.05),and 8-hydroxy-2-deoxyguanosine(P=0.07)],higher levels of serum and milk NETs(P<0.05)and blood-milk barrier indicators,including serumβ-casein(P=0.05)and milk immunoglobulin G2(P=0.09),than those of low DSCC cows.In addition,lower concentrations of serum nutrient metabolites(cholesterol and albumin)(P<0.05)and a lower level of serum deoxyribonuclease I(P=0.09)were observed in high DSCC cows than in low DSCC cows.Among the assessments performed using levels of the three prepartum serum parameters(NETs,deoxyribonuclease I andβ-casein),the area under the curve(0.973)of NETs was the highest.In addition,the sensitivity(1.00)and specificity(0.93)were observed for the discrimination of these cows using NETs levels with a critical value of 32.2 ng/mL(P<0.05).Conclusions:The formation of NETs in blood in transition dairy cows may damage the integrity of the blood-milk barrier and thereby increase the risk for mastitis in postpartum cows.

New Forward Gated-Diode Technique for Separating Front Gate Interface- from Oxide-Traps Induced by Hot-Carrier-Stress in SOI-NMOSFETs

The front gate interface and oxide traps induced by hot carrier stress in SOI NMOSFETs are studied.Based on a new forward gated diode technique,the R G current originating from the front interface traps is measured,and then the densities of the interface and oxide traps are separated independently.The experimental results show that the hot carrier stress of front channel not only results in the strong generation of the front interface traps,but also in the significant oxide traps.These two kinds of traps have similar characteristic in increasing with the hot carrier stress time.This analysis allows one to obtain a clear physical picture of the effects of the hot carrier stress on the generating of interface and oxide traps,which help to understand the degradation and reliability of the SOI MOSFETs.

Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis

Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

BACKGROUND The development of venous thromboembolism(VTE) is associated with high mortality among gastric cancer(GC) patients. Neutrophil extracellular traps(NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients.AIM To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients.METHODS The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells(ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity(PCA) was determined by fibrin formation and thrombin–antithrombin complex(TAT) assays.Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava(IVC).RESULTS NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and Pselectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumorbearing mice compared with control mice. Notably, the combination of deoxyribonuclease I,activated protein C, and sivelestat markedly abolished the PCA of NETs.CONCLUSION GC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.

Do neutrophil extracellular traps contribute to the heightened risk of thrombosis in inflammatory diseases?

Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and antiphospholipid syndrome,predispose to thrombosis,and thereby push the risk for these morbid events even higher. In recent years,neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically,chromatin-based structures called neutrophil extracellular traps(NETs) play a key role in activating the coagulation cascade,recruiting platelets,and serving as scaffolding upon which the thrombus can be assembled. At the same time,neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here,we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus,ANCA-associated vasculitis,and antiphospholipid syndrome.

Neutrophil extracellular traps in gastrointestinal cancer

Gastrointestinal(GI)cancer is a high-risk malignancy and is characterized by high mortality and morbidity worldwide.Neutrophil extracellular traps(NETs),a weblike structure consisting of chromatin DNA with interspersed cytoplasmic and granule proteins,are extruded by activated neutrophils to entrap and kill bacteria and fungi.However,accumulating evidence shows that NETs are related to the progression and metastasis of cancer.In clinical studies,NETs infiltrate primary GI cancer tissues and are even more abundant in metastatic lesions.The quantity of NETs in peripheral blood is revealed to be associated with ascending clinical tumour stages,indicating the role of NETs as a prognostic markers in GI cancer.Moreover,several inhibitors of NETs or NET-related proteins have been discovered and used to exert anti-tumour effects in vitro or in vivo,suggesting that NETs can be regarded as targets in the treatment of GI cancer.In this review,we will focus on the role of NETs in gastric cancer and colorectal cancer,generalizing their effects on tumour-related thrombosis,invasion and metastasis.Recent reports are also listed to show the latest evidences of how NETs affect GI cancer.Additionally,notwithstanding the scarcity of systematic studies elucidating the underlying mechanisms of the interaction between NETs and cancer cells,we highlight the potential importance of NETs as biomarkers and anti-tumour therapeutic targets.

Distribution and controls of petroliferous plays in subtle traps within a Paleogene lacustrine sequence stratigraphic framework, Dongying Depression, Bohai Bay Basin, Eastern China

The characteristics of petroliferous plays in subtle traps within a sequence stratigraphic framework in the Dongying Depression are investigated in this study.Sand bodies within lowstand systems tracts(LSTs)of sequences,comprising incisedchannel fills,sublacustrine fans,deltas in LSTs,controlled by syndepositional normal faults,and sand bodies within transgressive systems tracts(TSTs)to early highstand systems tracts(HSTs),consisting of beach bars,and turbidites,controlled by the prodelta slope,paleorelief,and syndepositional normal faults,are good subtle reservoirs.Mudstones and shale of deep lake subfacies in TSTs to early HSTs of sequences are source and cap rocks.Abnormal overpressure is the dominant dynamic factor for hydrocarbon migration from source rock to the subtle traps.Normal faults,sand bodies,and unconformities function as conduit systems.Sand bodies distributed in the abnormal overpressure source rocks within LSTs to early HSTs are petroliferous plays in lithologic traps.The petroliferous plays in stratigraphic traps are controlled by unconformities at margins of the Depression.

2D study of AlGaN/AlN/GaN/AlGaN HEMTs' response to traps

In this work, the effects of GaN channel traps and temperature on the performance of AlGaN/AlN/GaN/AlGaN high electron mobility transistors(HEMTs) on Si(111) substrate, were investigated. 2 D simulations carried out using the Silvaco TCAD simulator tool for different drain and gate voltages showed that acceptor-like traps in the channel have a significant influence on the DC and RF characteristics. It was found that deeper acceptors below the conduction band with larger concentration have a more pronounced effect on the transistor performance. Meanwhile, the donor-like traps show no influence. Pulsing the device with different pulse widths and bias conditions, as well as increasing temperature, showed that the traps are more ionized when the pulse is wider or the temperature is higher, which can degrade the drain current and thus the DC characteristics of the transistor. Passivation of the transistor has also a beneficial effect on performance.

Investigation of current collapse and recovery time due to deep level defect traps inβ-Ga2O3 HEMT

In this paper,drain current transient characteristics ofβ-Ga2O3 high electron mobility transistor(HEMT)are studied to access current collapse and recovery time due to dynamic population and de-population of deep level traps and interface traps.An approximately 10 min,and 1 h of recovery time to steady-state drain current value is measured under 1 ms of stress on the gate and drain electrodes due to iron(Fe)–dopedβ-Ga2O3 substrate and germanium(Ge)–dopedβ-Ga2O3 epitaxial layer respectively.On-state current lag is more severe due to widely reported defect trap EC–0.82 e V over EC–0.78 e V,-0.75 e V present in Iron(Fe)-dopedβ-Ga2O3 bulk crystals.A negligible amount of current degradation is observed in the latter case due to the trap level at EC–0.98 e V.It is found that occupancy of ionized trap density varied mostly under the gate and gate–source area.This investigation of reversible current collapse phenomenon and assessment of recovery time inβ-Ga2O3 HEMT is carried out through 2 D device simulations using appropriate velocity and charge transport models.This work can further help in the proper characterization ofβ-Ga2O3 devices to understand temporary and permanent device degradation.

Neutrophil extracellular traps in the intestinal mucosa of Eimeria-infected animals

Objective:To investigate the presence of neutrophil extracellular traps(NETs) in vivo by analysing intestinal sections from experimentally Eimeria bovis-and naturally Eimeria arloingi-infected animals.Methods:Intestinal samples of Eimeria arloingi-and Eimeria bovis-infected animals were analysed by using immunohistochemical and fluorescence approach by using monoclonal antibodies.Results:Classical NET components were confirmed by co-localization of extracellular DNA being decorated with neutrophil elastase and histones in Eimeria-infected tissue samples.Here,extrusion of NETs was exclusively detected in intestinal polymorphonuclear neutrophils infiltrating Eimeria-infected sites.In vivo NETs were either found in close proximity or in direct contact to different Eimeria stages suggesting a stage-independent process.NETs were also found within the gut lumen driven by polymorphonuclear neutrophils that were contacting released oocysts.Conclusions:We postulate that NETs might play an important role in innate defence reactions in coccidiosis therefore significantly altering the outcome of infection.

High-mobility SiC MOSFET with low density of interface traps using high pressure microwave plasma oxidation

The microwave plasma oxidation under the relatively high pressure(6 kPa)region is introduced into the fabrication process of SiO2/4 H-SiC stack.By controlling the oxidation pressure,species,and temperature,the record low density of interface traps(~4×10^(10)cm^(-2)·eV^(-1)@Ec-0.2 eV)is demonstrated on SiO2/SiC stack formed by microwave plasma oxidation.And high quality SiO2 with very flat interface(0.27-nm root-mean-square roughness)is obtained.High performance Si C metal–oxide–semiconductor field-effect transistors(MOSFETs)with peak field effect mobility of 44 cm^(-2)·eV^(-1)is realized without additional treatment.These results show the potential of a high-pressure plasma oxidation step for improving the channel mobility in SiC MOSFETs.

Tectonic significance of dykes in the Sarnu-Dandali alkaline complex,Rajasthan, northwestern Deccan Traps

Whether swarms of preferentially oriented dykes are controlled by regional stress fields, or passively exploit basement structural fabric, is a much debated question, with support for either scenario in individual case studies. The Sarnu-Dandali alkaline complex, near the northwestern limit of the Deccan Traps continental flood basalt province, contains mafic to felsic alkaline volcano-plutonic rocks and carbonatites. The complex is situated near the northern end of the 600 km long, NNWe SSE-trending Barmer-Cambay rift. Mafic enclave swarms in the syenites suggest synplutonic mafic dykes injected into a largely liquid felsic magma chamber. Later coherent dykes in the complex, of all compositions and sizes,dominantly strike NNWe SSE, parallel to the Barmer-Cambay rift. The rift formed during two distinct episodes of extension, NWe SE in the early Cretaceous and NEe SW in the late Cretaceous. Control of the southern Indian Dharwar structural fabric on the rift trend, as speculated previously, is untenable,whereas the regional Precambrian basement trends（Aravalli and Malani） run NEe SW and NNEe SSW.We therefore suggest that the small-scale Sarnu-Dandali dykes and the much larger-scale BarmerCambay rift were not controlled by basement structure, but related to contemporaneous, late Cretaceous regional ENEe WSW extension, for which there is varied independent evidence.

Quench Dynamics of Bose–Einstein Condensates in Boxlike Traps

By quenching the interatomic interactions, we investigate the nonequilibrium dynamics of two-dimensional Bose–Einstein condensates in boxlike traps with power-law potential boundaries. We show that ring dark solitons can be excited during the quench dynamics for both concave and convex potentials. The quench's modulation strength and the steepness of the boundary are two major factors influencing the system's evolution. In terms of the number of ring dark solitons excited in the condensate, five dynamic regimes have been identified. The condensate undergoes damped radius oscillation in the absence of ring dark soliton excitations. When it comes to the appearance of ring dark solitons, their decay produces interesting structures. The excitation patterns for the concave potential show a nested structure of vortex-antivortex pairs. The dynamic excitation patterns for the convex potential, on the other hand, show richer structures with multiple transport behaviors.

FORWARD GATED-DIODE METHOD FOR DIRECTLY MEASURING STRESS-INDUCED INTERFACE TRAPS IN NMOSFET/SOI

Forward gated-diode Recombination-Generation(R-G) current method is applied to an NMOSFET/SOI to measure the stress-induced interface traps in this letter. This easy but accurate experimental method can directly give stress-induced average interface traps for characterizing the device’s hot carrier characteristics. For the tested device, an expected power law relationship of △Nit-t0.787 between pure stress-induced interface traps and accumulated stressing time is obtained.

Attraction of <i>Idioscopus clypealis</i>(Leith) (Cicadellidae: Homoptera) to Sticky Colored Traps in Mango Orchard

The present study was conducted at the Faiz Chaman mango orchard, Multan to find out the attraction of mango hopper Idioscopus clypealis to sticky traps of different colors. The experiment was laid out in randomized complete block designed with three replications. The sticky traps were hung vertically with the branch/twig under the canopy of mango trees. Data were recorded under binocular stereoscope. Results indicated significant differences in the number of I. clypealis (adults) captured in the different colored sticky traps. Yellow color was found most attractive with a capture of highest number of adults of I. clypealis (11.53 adults/trap). While pink and purple colors were found less attractive. The peak population of mango hoppers was recorded at the 31.96&degC during 25-April to 9-May. Yellow sticky traps were found most effective in trapping a considerably higher number of hoppers throughout the study period. Correlation analysis revealed a strong positive correlation between temperature and the mean number of I. clypealis adults. Population peaks of I. clypealis were recorded at temperatures >30&degC, while at lower temperatures relatively low numbers of adults were recorded.

Carbon-Induced Deep Traps Responsible for Current Collapse in AlGaN/GaN HEMTs

Although outstanding microwave power performance of AlGaN/GaN HEMTs has been reported,drain current collapse is still a problem. In this paper,an experiment was carried out to demonstrate one factor causing the collapse. Two AlGaN/GaN samples were annealed under N2-atmosphere with and without carbon incorporation, and the XPS measurement technique was used to determine that the concentration of carbon impurity in the latter sample was far higher than in the former. From the comparison of two Id- Vds characteristics,we conclude that carbon impurity incorporation is responsible for the severe current collapse. The carbon impurity-induced deep traps under negative gate bias stress can capture the channel carriers, which release slowly from these traps under positive bias stress,thus causing the current collapse.