Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins...Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins released by neutrophils,contribute significantly to both inflammation and thrombosis.This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis,highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD.Notably,the impact of radiation on NET formation is explored,emphasising how oxidative stress and inflammatory responses drive NET release,contributing to plaque instability.The role of histones,particularly citrullinated histones,in endothelial dysfunction and plaque progression is discussed,highlighting their significance in the pathophysiology of atherosclerosis.Furthermore,the complex relationship between lipoproteins and NET formation is examined,with a focus on how elevated low-density lipoprotein(LDL)and decreased high-density lipoprotein(HDL)levels facilitate NET release,thus promoting vascular inflammation and plaque instability.The influence of cholesterol on NET formation is also explored,underscoring its contribution to plaque development and stability.The role of Peptidylarginine deiminase 4(PAD4)in the regulation of NETosis is reviewed,with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression.Moreover,the manuscript examines the potential of NET components—such as double-stranded DNA,myeloperoxidase–DNA complexes,and citrullinated histone H3—as biomarkers for assessing disease severity and predicting adverse cardiovascular events,including ST-elevation myocardial infarction(STEMI)and stroke.Elevated levels of these biomarkers correlate with worse clinical outcomes,suggesting their utility in guiding therapeutic interventions.In contrast to the existing body of work,this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism,histone modifications,and PAD4 activity in the context of atherosclerosis.Overall,NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis,and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.展开更多
Large-scale Danian-age(post-K/Pg boundary)Deccan magmatism is well known from the Mumbai metropolitan area,located in the structurally complex Panvel flexure zone along the western Indian rifted continental margin.Thi...Large-scale Danian-age(post-K/Pg boundary)Deccan magmatism is well known from the Mumbai metropolitan area,located in the structurally complex Panvel flexure zone along the western Indian rifted continental margin.This compositionally diverse late-Deccan magmatic suite contains subaerial tholeiitic lavas and dykes typical of the main Deccan province,with many features atypical of the Deccan,such as spilitic pillow lavas,“intertrappean”sediments(often containing considerable volcanic ash),rhyolitic lavas and tuffs,gabbro-granophyre intrusions,and trachyte intrusions containing alkali basalt enclaves.Most of these units,previously dated at 62.5 Ma to 61 Ma,are contemporaneous with or slightly postdate the 62.5 Ma India-Seychelles continental breakup and Panvel flexure formation.In the Dongri-Uttan area,two samples of a>50-m-thick,columnar-jointed rhyolite from the Darkhan Quarry and from a section behind the current Uttan Sagari Police Station have previously been dated at 62.6±0.6 Ma and 62.9±0.2 Ma(^(40)Ar/^(39)Ar,2r errors).New exposures reveal that these two statistically indistinguishable 40 Ar/39 Ar ages correspond to two distinct rhyolite units,separated by well-bedded silicic ash.The columnar rhyolites are microcrystalline,composed of quartz and alkali feldspar,with rare small(1–2 mm),altered feldspar phenocrysts,and no recognisable relict vitroclasts.Given the westerly structural dip,most of their lateral extent is submerged under the Arabian Sea,and we consider them to be possible flood rhyolite lavas.We interpret the ash beds,composed of pumice clasts and glass shards,as a low-grade(nonwelded)vitric ash,derived from a possibly distal Plinian eruption and deposited by fallout.The lavas and ash are peraluminous rhyolites.The lavas are Sr-Ba-poor and Rb-Zr-Nb-rich,and show“seagull-shaped”rare earth element patterns with deep negative europium anomalies.These crystal-poor lavas are“hot-dry-reduced”rhyolites typical of intraplate,continental rift and rifted margin settings.The very different high-field strength element contents of the lavas and the ash indicate compositionally distinct magma batches.The 62.5 Ma Dongri-Uttan sequence provides clear evidence for rapid silicic eruptions of effusive and explosive nature,alternating with each other and sourced from distinct magma chambers and eruptive vents.A newly identified,highly feldspar-phyric trachyte intrusion marks the last phase of magmatic activity in the area,corresponding with late-stage trachyte-syenite intrusions exposed in coastal western India and the Seychelles,and shows that the Mumbai rhyolites and trachytes form a compositional continuum.展开更多
In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to elimin...In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.展开更多
Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as...Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.展开更多
Scintillator is a key material for the development of X-ray detectors,which has a promising application in medical imaging,security inspection and industrial non-injury detection.The majority of scintillators currentl...Scintillator is a key material for the development of X-ray detectors,which has a promising application in medical imaging,security inspection and industrial non-injury detection.The majority of scintillators currently used in imaging are real-time imaging scintillators,which can cause ionization radiation damage to biological subjects or detection equipment during the imaging process and require complex,highly sensitive detection systems.Therefore,exploring stable,environmentally friendly scintillator materials that can achieve delayed imaging is of significance in the field of imaging.Herein,we devel-oped an X-ray time-lapse imaging scintillator,Sr_(2)Al_(6)O_(11):Dy^(3+)phosphor,which generates stable traps by X-ray irradiation,thus endowing it with excellent persistent luminescence and information storage properties(>42 d).Moreover,traps constructed by X-ray can be repeatedly refilled(>40 times)under UV light and carriers are released in theform of mechanical or thermal excitation when refilling is complete.By constructing the traps in the phosphor during X-ray excitation and using it for repetitive imaging,the detection limit is 74.78 nGy/s,and the spatial imaging resolution is as high as 16 lp/mm.This discovery providesa new idea for the development oftime-delayed X-ray scintillator.展开更多
Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have r...Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.展开更多
Objective:Gemcitabine combined with nab-paclitaxel therapy(GnP)represents first-line chemotherapy for advanced pancreatic ductal adenocarcinoma(PDAC).However,the efficacy of GnP is diminished due to chemotherapeutic r...Objective:Gemcitabine combined with nab-paclitaxel therapy(GnP)represents first-line chemotherapy for advanced pancreatic ductal adenocarcinoma(PDAC).However,the efficacy of GnP is diminished due to chemotherapeutic resistance induced by the tumor microenvironment(TME),the underlying mechanisms of which remain poorly understood.Methods:Clinical data from patients with PDAC who underwent GnP therapy were collected and neutrophil infiltration in tumor tissues was assessed.PDAC cell lines and a mouse model of PDAC were utilized to determine the mechanisms underlying GnP resistance and to focus on tumor-associated neutrophils and neutrophil extracellular traps(NETs).Results:GnP therapy recruited neutrophils to the TME,which resulted in the formation of NETs that contributed to therapeutic resistance in the PDAC murine model.The NET inhibitor,PAD4,enhanced the efficacy of GnP by suppressing tumor growth.Furthermore,GnP significantly upregulated CXCL8 secretion in GnP-resistant MIA PaCa-2 cells,which was mediated by increased expression of GPRC5A in PDAC cells.Screening of classic NET-derived molecules identified cell-free DNA(cfDNA)as a pleiotropic factor that promoted tumor cell proliferation and migration and thereby contributed to chemotherapeutic resistance.In vivo experiments revealed that the combination of GnP with si GPRC5A or DNase was more effective in reducing tumor growth and prolonging survival in PDAC-bearing mice than either treatment alone.Conclusion:The GPRC5A-CXCL8-NET-cfDNA axis has a critical role in the development of therapeutic resistance to GnP in PDAC.Targeting this axis may represent a promising strategy for overcoming GnP resistance and thereby enhancing the efficacy of chemotherapy in PDAC.展开更多
Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.Mo...Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.More effective medical interventions,including those involving traditional Chinese medicine,could be beneficial for patients with newly diagnosed colorectal cancer to prevent the progression to liver metastasis.Xiaoyaosan(XYS)is a classical prescription in traditional Chinese medicine with a history of hundreds of years.Despite its well-known protective effects against breast cancer,the understanding of its application in colorectal cancer metastases remains limited.The anti-metastasis mechanism of XYS remains to be elucidated.In this research,we explored the impact of XYS against liver metastases of colorectal cancer and its potential mechanisms.Methods:Thirty-six SPF male C57BL/6 mice were randomly assigned to six groups:a control group,a model group,a DNase I group,and three XYS treatment groups receiving high,medium,and low doses,respectively.A mouse model for colorectal cancer liver metastasis was established through the splenic injection of MC38 cells.Twenty-one days after the injection of cancer cells,the number of metastatic foci and the weights of the liver were calculated,and HE staining was performed to evaluate the effect of XYS.Neutrophil extracellular traps(NETs)formation in the liver was detected by immunofluorescence staining,and NETs formation in the serum was detected by ELISA.The levels of CXCL1,CXCL2,G-CSF,and HMGB1 were determined using ELISA kits.The expression levels of the proteins p-p38,p38,p-ERK,and ERK were assessed using Western blot analysis.Results:XYS treatment reduced the number of metastatic foci,the weights of metastatic livers,and the infiltration area of tumor-like cells.XYS could inhibit NETs formation in the liver and serum of mice with metastasis.The concentrations of CXCL1,CXCL2,G-CSF,and HMGB1 were significantly decreased in all XYS-treated groups.Moreover,XYS down-regulated the protein expression levels of phosphorylated p38 and ERK.Conclusion:XYS could attenuate liver metastases of colorectal cancer in vivo.The inhibitory mechanism of XYS may involve the reduction of NETs formation through the regulation of tumor-derived factors and the downstream MAPKs(p38,ERK)signaling pathway.展开更多
BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy co...BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.展开更多
Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the deve...Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the development and progression of ALI.During ALI,neutrophils generate neutrophil extracellular traps(NETs),and excessive NETs can intensify inflammatory injury.Research indicates that Taohe Chengqi decoction(THCQD)can ameliorate sepsis-induced lung inflammation and modulate immune function.This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients,seeking to provide novel perspectives and interventions for clinical treatment.The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture(CLP)-induced ALI mouse model.Furthermore,THCQD diminished neutrophil and macrophage infiltration,inflammatory responses,and the production of pro-inflammatory cytokines,including interleukin-1β(IL-1β),IL-6,and tumor necrosis factorα(TNF-α).Notably,subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro.Moreover,THCQD significantly decreased the expression of peptidyl arginine deiminase 4(PAD4)protein,and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4.PAD4 overexpression partially reversed THCQD’s inhibitory effects on PAD4.These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.展开更多
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 me...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.展开更多
Unconventional natural gas has become an important supplement to conventional energy sources,and the process of enrichment and purification of methane from low concentration coalbed methane is crucial.To this end,we r...Unconventional natural gas has become an important supplement to conventional energy sources,and the process of enrichment and purification of methane from low concentration coalbed methane is crucial.To this end,we report a copper-based metal-organic framework(MOF),ZJNU-119Cu,featuring two methane traps constructed with uncoordinated carboxylic acid oxygens and open metal sites.ZJNU-119Cu exhibits a high methane adsorption capacity(58.2 cm^(3)·g^(-1))at 298 K and 0.1 MPa and excellent CH_(4)/N_(2) separation performance under dynamic conditions.Densityfunctional theory calculations combined with grand canonical Monte Carlo simulation theory reveal the interaction mechanism for the uncoordinated carboxylic acid oxygen atoms and open metal sites in ZJNU-119Cu with CH4.The gas adsorption isotherms,heat of adsorption calculations,and breakthrough separation experiments indicate that this MOF is a very promising adsorbent for CH_(4)/N_(2) separation.展开更多
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 involveme...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.展开更多
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 prothromboti...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.展开更多
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 an...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.展开更多
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 extracellu...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.展开更多
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 intersperse...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.展开更多
This study demonstrates the preparation and characterization of a novel ion imprinted cryogel which exhibits high affinity and selectivity towards Ce（Ⅲ） ions in aqueous solutions and bastnasite ore samples.2-Hydrox...This study demonstrates the preparation and characterization of a novel ion imprinted cryogel which exhibits high affinity and selectivity towards Ce（Ⅲ） ions in aqueous solutions and bastnasite ore samples.2-Hydroxyethyl methacrylate（HEMA） and N-methacryloylamido antipyrine（MAAP） were used as functional monomers for the preparation of Ce（Ⅲ） imprinted cryogel. The effects of various factors such as initial Ce（Ⅲ） concentration, flow rate, pH, interaction time and ionic strength on the Ce（Ⅲ） binding to the prepared ion imprinted cryogels were also studied. The binding equilibrium for Ce（Ⅲ） is obtained in30 min at the flow rate of 0.5 mL/min. The maximum binding capacity of the prepared ion imprinted cryogel towards Ce（Ⅲ） is obtained as 36.58 mg/g at optimum conditions. The selectivity of the prepared ion imprinted cryogel towards Ce（Ⅲ） in the presence of other possible interfering lanthanide ions such as La（Ⅲ） and Nd（Ⅲ） were also performed. The obtained results showed that the prepared ion imprinted cryogel exhibits high selectivity and sensitivity towards Ce（Ⅲ） ions. The limit of detection（LOD） was found as 50 μg/L.展开更多
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 t...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.展开更多
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by NIH grants to MI Bukrinsky(R01NS124477 and P30AI117970)by the“Creation of Experimental Laboratories in the Natural Sciences Program”and Basic Research Programat Higher School of Economics University.
文摘Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins released by neutrophils,contribute significantly to both inflammation and thrombosis.This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis,highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD.Notably,the impact of radiation on NET formation is explored,emphasising how oxidative stress and inflammatory responses drive NET release,contributing to plaque instability.The role of histones,particularly citrullinated histones,in endothelial dysfunction and plaque progression is discussed,highlighting their significance in the pathophysiology of atherosclerosis.Furthermore,the complex relationship between lipoproteins and NET formation is examined,with a focus on how elevated low-density lipoprotein(LDL)and decreased high-density lipoprotein(HDL)levels facilitate NET release,thus promoting vascular inflammation and plaque instability.The influence of cholesterol on NET formation is also explored,underscoring its contribution to plaque development and stability.The role of Peptidylarginine deiminase 4(PAD4)in the regulation of NETosis is reviewed,with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression.Moreover,the manuscript examines the potential of NET components—such as double-stranded DNA,myeloperoxidase–DNA complexes,and citrullinated histone H3—as biomarkers for assessing disease severity and predicting adverse cardiovascular events,including ST-elevation myocardial infarction(STEMI)and stroke.Elevated levels of these biomarkers correlate with worse clinical outcomes,suggesting their utility in guiding therapeutic interventions.In contrast to the existing body of work,this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism,histone modifications,and PAD4 activity in the context of atherosclerosis.Overall,NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis,and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.
基金supported by the research award project RI/0220-10000618-001 to Sheth from the Industrial Research and Consultancy Centre(IRCC)IIT Bombay.Shekhar and Astha were supported by Prime Minister’s Research Fellowships(PMRF,File Nos.1303100 and 1303103,respectively)+4 种基金Naik was initially supported by an IIT Bombay Institute Post-Doctoral Fellowship(File No.HR-1(HRM-1)/Rect/33/2022/20003002)subsequently by a Goa State Research Foundation Post-doctoral Fellowship(File No.PDF2024003)We express our sincere gratitude to Prof.N.Prabhakar for kindly granting us access to the WD-XRF spectrometry facility(SIP ProjectWBS Code:IN/22-1111039E-01)the ICP-MS facility,and the SERB-funded EPMA National Facility(IRPHA Grant No.IR/S4/ESF-16/2009(G))in the Department of Earth Sciences,IIT Bombay.
文摘Large-scale Danian-age(post-K/Pg boundary)Deccan magmatism is well known from the Mumbai metropolitan area,located in the structurally complex Panvel flexure zone along the western Indian rifted continental margin.This compositionally diverse late-Deccan magmatic suite contains subaerial tholeiitic lavas and dykes typical of the main Deccan province,with many features atypical of the Deccan,such as spilitic pillow lavas,“intertrappean”sediments(often containing considerable volcanic ash),rhyolitic lavas and tuffs,gabbro-granophyre intrusions,and trachyte intrusions containing alkali basalt enclaves.Most of these units,previously dated at 62.5 Ma to 61 Ma,are contemporaneous with or slightly postdate the 62.5 Ma India-Seychelles continental breakup and Panvel flexure formation.In the Dongri-Uttan area,two samples of a>50-m-thick,columnar-jointed rhyolite from the Darkhan Quarry and from a section behind the current Uttan Sagari Police Station have previously been dated at 62.6±0.6 Ma and 62.9±0.2 Ma(^(40)Ar/^(39)Ar,2r errors).New exposures reveal that these two statistically indistinguishable 40 Ar/39 Ar ages correspond to two distinct rhyolite units,separated by well-bedded silicic ash.The columnar rhyolites are microcrystalline,composed of quartz and alkali feldspar,with rare small(1–2 mm),altered feldspar phenocrysts,and no recognisable relict vitroclasts.Given the westerly structural dip,most of their lateral extent is submerged under the Arabian Sea,and we consider them to be possible flood rhyolite lavas.We interpret the ash beds,composed of pumice clasts and glass shards,as a low-grade(nonwelded)vitric ash,derived from a possibly distal Plinian eruption and deposited by fallout.The lavas and ash are peraluminous rhyolites.The lavas are Sr-Ba-poor and Rb-Zr-Nb-rich,and show“seagull-shaped”rare earth element patterns with deep negative europium anomalies.These crystal-poor lavas are“hot-dry-reduced”rhyolites typical of intraplate,continental rift and rifted margin settings.The very different high-field strength element contents of the lavas and the ash indicate compositionally distinct magma batches.The 62.5 Ma Dongri-Uttan sequence provides clear evidence for rapid silicic eruptions of effusive and explosive nature,alternating with each other and sourced from distinct magma chambers and eruptive vents.A newly identified,highly feldspar-phyric trachyte intrusion marks the last phase of magmatic activity in the area,corresponding with late-stage trachyte-syenite intrusions exposed in coastal western India and the Seychelles,and shows that the Mumbai rhyolites and trachytes form a compositional continuum.
文摘In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.
基金supported by the National Natural Science Foundation of China(Grant nos.82473157,82460510,82203565,82103388,31960145 and 82560591)the Natural Science Foundation of Beijing(Grant no.L248059)+1 种基金Yunnan Province applied research funds(Grant nos.202201AY070001-011,202201AY070001-043,and 202301AS070018)the Science and Technology Innovation Team of tumor metabolism research at Kunming Medical University(Grant no.CXTD202102).
文摘Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.
基金the National Natural Science Foundation of China(12364044)Yunnan Major Scientific and Technological Projects(202202AG050004,202202AG050016,202302AQ370003)+1 种基金the International Joint Innovation Platform of Yunnan Province(202203AP140004)the Outstanding Youth Project of Yunnan Province Applied Basic Research Project(202401AV070012).
文摘Scintillator is a key material for the development of X-ray detectors,which has a promising application in medical imaging,security inspection and industrial non-injury detection.The majority of scintillators currently used in imaging are real-time imaging scintillators,which can cause ionization radiation damage to biological subjects or detection equipment during the imaging process and require complex,highly sensitive detection systems.Therefore,exploring stable,environmentally friendly scintillator materials that can achieve delayed imaging is of significance in the field of imaging.Herein,we devel-oped an X-ray time-lapse imaging scintillator,Sr_(2)Al_(6)O_(11):Dy^(3+)phosphor,which generates stable traps by X-ray irradiation,thus endowing it with excellent persistent luminescence and information storage properties(>42 d).Moreover,traps constructed by X-ray can be repeatedly refilled(>40 times)under UV light and carriers are released in theform of mechanical or thermal excitation when refilling is complete.By constructing the traps in the phosphor during X-ray excitation and using it for repetitive imaging,the detection limit is 74.78 nGy/s,and the spatial imaging resolution is as high as 16 lp/mm.This discovery providesa new idea for the development oftime-delayed X-ray scintillator.
基金the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Yantai Science and Technology Program,No.2024YD005,No.2024YD007 and No.2024YD010and Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.
基金supported by the National Natural Science Foundation of China(Grant Nos.82271883 and 82073195 to Qing.Xiaand 82471775 and 82271800 to Yuli.Lin)+3 种基金the Hospital-pharma Integration Project on Innovative Achievement Translation(Grant No.SHDC2022CRD043 to Qing.Xia)the Shanghai Jiao Tong University School of Medicine Summit Program-“Research Physician”in Clinical Medicine to Qing.Xiathe Young Physician-Scientist Cultivation Program of Shanghai Immune Therapy Institute to Qing.Xiathe Light of the Lintel-young Talents of Huangpu to Qing.Xia。
文摘Objective:Gemcitabine combined with nab-paclitaxel therapy(GnP)represents first-line chemotherapy for advanced pancreatic ductal adenocarcinoma(PDAC).However,the efficacy of GnP is diminished due to chemotherapeutic resistance induced by the tumor microenvironment(TME),the underlying mechanisms of which remain poorly understood.Methods:Clinical data from patients with PDAC who underwent GnP therapy were collected and neutrophil infiltration in tumor tissues was assessed.PDAC cell lines and a mouse model of PDAC were utilized to determine the mechanisms underlying GnP resistance and to focus on tumor-associated neutrophils and neutrophil extracellular traps(NETs).Results:GnP therapy recruited neutrophils to the TME,which resulted in the formation of NETs that contributed to therapeutic resistance in the PDAC murine model.The NET inhibitor,PAD4,enhanced the efficacy of GnP by suppressing tumor growth.Furthermore,GnP significantly upregulated CXCL8 secretion in GnP-resistant MIA PaCa-2 cells,which was mediated by increased expression of GPRC5A in PDAC cells.Screening of classic NET-derived molecules identified cell-free DNA(cfDNA)as a pleiotropic factor that promoted tumor cell proliferation and migration and thereby contributed to chemotherapeutic resistance.In vivo experiments revealed that the combination of GnP with si GPRC5A or DNase was more effective in reducing tumor growth and prolonging survival in PDAC-bearing mice than either treatment alone.Conclusion:The GPRC5A-CXCL8-NET-cfDNA axis has a critical role in the development of therapeutic resistance to GnP in PDAC.Targeting this axis may represent a promising strategy for overcoming GnP resistance and thereby enhancing the efficacy of chemotherapy in PDAC.
基金supported by Sichuan Science and Technology Program(grant number 2023NSFSC1809)Hospital of Chengdu University of Traditional Chinese Medicine(grant number 23ZYTS1004,21YY01).
文摘Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.More effective medical interventions,including those involving traditional Chinese medicine,could be beneficial for patients with newly diagnosed colorectal cancer to prevent the progression to liver metastasis.Xiaoyaosan(XYS)is a classical prescription in traditional Chinese medicine with a history of hundreds of years.Despite its well-known protective effects against breast cancer,the understanding of its application in colorectal cancer metastases remains limited.The anti-metastasis mechanism of XYS remains to be elucidated.In this research,we explored the impact of XYS against liver metastases of colorectal cancer and its potential mechanisms.Methods:Thirty-six SPF male C57BL/6 mice were randomly assigned to six groups:a control group,a model group,a DNase I group,and three XYS treatment groups receiving high,medium,and low doses,respectively.A mouse model for colorectal cancer liver metastasis was established through the splenic injection of MC38 cells.Twenty-one days after the injection of cancer cells,the number of metastatic foci and the weights of the liver were calculated,and HE staining was performed to evaluate the effect of XYS.Neutrophil extracellular traps(NETs)formation in the liver was detected by immunofluorescence staining,and NETs formation in the serum was detected by ELISA.The levels of CXCL1,CXCL2,G-CSF,and HMGB1 were determined using ELISA kits.The expression levels of the proteins p-p38,p38,p-ERK,and ERK were assessed using Western blot analysis.Results:XYS treatment reduced the number of metastatic foci,the weights of metastatic livers,and the infiltration area of tumor-like cells.XYS could inhibit NETs formation in the liver and serum of mice with metastasis.The concentrations of CXCL1,CXCL2,G-CSF,and HMGB1 were significantly decreased in all XYS-treated groups.Moreover,XYS down-regulated the protein expression levels of phosphorylated p38 and ERK.Conclusion:XYS could attenuate liver metastases of colorectal cancer in vivo.The inhibitory mechanism of XYS may involve the reduction of NETs formation through the regulation of tumor-derived factors and the downstream MAPKs(p38,ERK)signaling pathway.
文摘BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.
基金supporteded by the National Natural ScienceFoundation of China(Nos.82374183,82405092,82204991,82274246,and 82374341)the Planned Science TechnologyProjectofGuangzhouCity(Nos.2023A03J0419and2023A03J0420)+3 种基金the General Project of Natural Science Foundationof Guangdong Province(No.2023A1515011090)Hong KongScholars Program 2024(No.XJ2024005)the Basic and AppliedBasic Research Foundation of Guangdong Province(No.2021A151510809)the Project of Administration of TraditionalChinese Medicine of Guangdong Province of China(No.20223013).
文摘Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the development and progression of ALI.During ALI,neutrophils generate neutrophil extracellular traps(NETs),and excessive NETs can intensify inflammatory injury.Research indicates that Taohe Chengqi decoction(THCQD)can ameliorate sepsis-induced lung inflammation and modulate immune function.This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients,seeking to provide novel perspectives and interventions for clinical treatment.The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture(CLP)-induced ALI mouse model.Furthermore,THCQD diminished neutrophil and macrophage infiltration,inflammatory responses,and the production of pro-inflammatory cytokines,including interleukin-1β(IL-1β),IL-6,and tumor necrosis factorα(TNF-α).Notably,subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro.Moreover,THCQD significantly decreased the expression of peptidyl arginine deiminase 4(PAD4)protein,and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4.PAD4 overexpression partially reversed THCQD’s inhibitory effects on PAD4.These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
文摘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.
基金financial support from the National Natural Science Foundation of China(22408258 and 22378287)the Joint Founds of the National Natural Science Foundation of China(U20B6004)the Natural Science Foundation of Shanxi Province(202303021222012).
文摘Unconventional natural gas has become an important supplement to conventional energy sources,and the process of enrichment and purification of methane from low concentration coalbed methane is crucial.To this end,we report a copper-based metal-organic framework(MOF),ZJNU-119Cu,featuring two methane traps constructed with uncoordinated carboxylic acid oxygens and open metal sites.ZJNU-119Cu exhibits a high methane adsorption capacity(58.2 cm^(3)·g^(-1))at 298 K and 0.1 MPa and excellent CH_(4)/N_(2) separation performance under dynamic conditions.Densityfunctional theory calculations combined with grand canonical Monte Carlo simulation theory reveal the interaction mechanism for the uncoordinated carboxylic acid oxygen atoms and open metal sites in ZJNU-119Cu with CH4.The gas adsorption isotherms,heat of adsorption calculations,and breakthrough separation experiments indicate that this MOF is a very promising adsorbent for CH_(4)/N_(2) separation.
基金supported by The National Natural Science Foundation of China(Grant No.81702972,Grant No.81874204)China Postdoctoral Science Foundation(Grant No.2018M640305,Grant No.2019M660074)+4 种基金The Research Project of the Chinese Society of Neuro-oncology,CACA(Grant No.CSNO-2016-MSD12)Heilongjiang Postdoctoral Science Foundation(Grant No.LBH-Z18103)The Research Project of the Health and Family Planning Commission of Heilongjiang Province(Grant No.2017–201)Postgraduate Research&Practice Innovation Program of Harbin Medical University(Grant No.YJSKYCX2018-94HYD)The Young and middle-aged Science Foundation of Harbin Medical University(Grant No.KYCX2018-08)。
文摘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.
基金Supported by National Natural Science Foundation of China,No.81672355.
文摘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.
基金Supported by NIH K08AR066569a career development award from the Burroughs Wellcome Fund(Knight JS)Kazzaz NM was supported by Security Forces Hospital Program,Ministry of Interior,Riyadh,Saudi Arabia
文摘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.
基金supported by the National Natural Science Foundation of China,No.82271399(to XC)the Project of Tianjin Applied Basic and Multiple Support Research,No.21JCZDJC00910(to XC)+4 种基金the Scientific Research Program of Tianjin Education Commission(Natural Science)of China,No.2019ZD034(to QD)the Science&Technology Program of Tianjin for Cultivation of Innovative Talents,No.22JRRCRC00020(to QD)the Tianjin Medical University"Clinical Talent Training 123 Climbing Plan"(to XC)the Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)。
文摘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.
基金Supported by Natural Science Foundation of Beijing for Youth,No.7214252Program of Military Medicine for Youth,No.QNF19055.
文摘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.
文摘This study demonstrates the preparation and characterization of a novel ion imprinted cryogel which exhibits high affinity and selectivity towards Ce（Ⅲ） ions in aqueous solutions and bastnasite ore samples.2-Hydroxyethyl methacrylate（HEMA） and N-methacryloylamido antipyrine（MAAP） were used as functional monomers for the preparation of Ce（Ⅲ） imprinted cryogel. The effects of various factors such as initial Ce（Ⅲ） concentration, flow rate, pH, interaction time and ionic strength on the Ce（Ⅲ） binding to the prepared ion imprinted cryogels were also studied. The binding equilibrium for Ce（Ⅲ） is obtained in30 min at the flow rate of 0.5 mL/min. The maximum binding capacity of the prepared ion imprinted cryogel towards Ce（Ⅲ） is obtained as 36.58 mg/g at optimum conditions. The selectivity of the prepared ion imprinted cryogel towards Ce（Ⅲ） in the presence of other possible interfering lanthanide ions such as La（Ⅲ） and Nd（Ⅲ） were also performed. The obtained results showed that the prepared ion imprinted cryogel exhibits high selectivity and sensitivity towards Ce（Ⅲ） ions. The limit of detection（LOD） was found as 50 μg/L.
基金This work was supported by grants from Guangxi Medical High-level Key Talents/139/(No.G201901010)Natural Science Foundation of Guangxi Province(No.GXNSFDA198008).
文摘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.
