Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes rece...Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.展开更多
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
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
Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen spec...Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen species,degranulation,and NETosis(formation of neutrophil extracellular traps[NETs]).NETs,which contain antimicrobial compounds such as myeloperoxidase(MPO),represent a strategy to combat infection.However,excessive production of NETs promotes thrombosis,diabetes mellitus,and other diseases.Therefore,investigations into the mechanisms of NETosis and the identification of modulators of this process are critical for developing strategies to address NETosis-related disorders.Here,we identified a novel NETosis inducer,human serum albumin(HSA)modified by the MPO product hypochlorous acid(HSAHOCl),whose accumulation in vivo was correlated with inflammatory processes.Using human blood neutrophils,we investigated HSAHOCl-induced NETosis and detected NET formation by flow cytometry.The results showed that the mechanism of HSAHOClinduced NETosis involved MPO,NADPH oxidase,and phosphatidylinositol 3-kinases(PI3Ks),and that HSAHOCl activated a reactive oxygen species-dependent suicidal type of NETosis.Moreover,HSAHOCl-induced NETosis was inhibited by an anti-HSAHOCl monoclonal antibody.Thus,our findings may facilitate the development of strategies to modulate NETosis in inflammation associated with elevated MPO activity.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
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
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
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: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
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
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
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
Optical tweezers technology has the characteristics of noncontact manipulation in three dimensions and steerable separation in solutions,and could be applied to obtain a separated sperm with high quality for intracyto...Optical tweezers technology has the characteristics of noncontact manipulation in three dimensions and steerable separation in solutions,and could be applied to obtain a separated sperm with high quality for intracytoplasmic sperm injection(ICSI).However,the effects of optical tweezers on sperm motility are still unclear.To elucidate the effects on sperm motility for optical tweezers,we systematically investigated the correlation between motility parameters and the parameters of optical tweezers(wavelength,power,trapping duration,and trapping orientation).Under three systems of optical tweezers with different laser wavelengths(1064,850,and 785 nm),the nine motility parameters of free swimming were mainly affected by trapping orientation(vertical/horizontal)and trapping duration.When 850 nm laser and 1064 nm laser are used,vertical trapping significantly reduces sperm free-swimming capability with prolonged exposure time,whereas horizontal trapping exhibits relatively minor interference on sperm motility.Notably,the 785 nm laser does not induce statistically significant changes in key parameters of sperm motility under any experimental conditions(trapping orientation and duration).For the rolling frequency of trapped sperm,horizontal trapping for three wavelengths has a negligible effect compared with vertical trapping,especially for the 785 nm laser.In conclusion,horizontal trapping can preserve sperm motility under low power(below 140mW at 1064 nm,below 100mW at 850nm,below 60mW at 785 nm)and short duration(below 4 min).This trapping duration is suffcient for the separation procedure of single live sperm in ICSI.This study provides critical parameter optimization guidelines for the safe application of optical tweezers technology in reproductive medicine.展开更多
Diabetic nephropathy(DN)begins with diabetes-related disruptions in glucose metabolism,with oxidative stress playing a crucial role.Neutrophil extracellular traps(NETs)are extensive web-like formations composed of cyt...Diabetic nephropathy(DN)begins with diabetes-related disruptions in glucose metabolism,with oxidative stress playing a crucial role.Neutrophil extracellular traps(NETs)are extensive web-like formations composed of cytosolic and granule proteins,which are dependent on oxidative stress for their formation and function.This study aimed to identify potential targets for DN progression,focusing on NETs,using bioinformatic analysis and quantitative Real-Time PCR(qRT-PCR).We performed differential gene expression(DEG)analysis on two DN-related RNA-seq datasets(GSE142025 and GSE163603)and NETs-related genes.Subsequent analysis included gene set enrichment analysis(GSEA),gene set variation analysis(GSVA),GeneMANIA,and receiver operating characteristic(ROC)curves.Immune cell infiltration levels were assessed via single-sample GSEA,and a regulatory network involving RNA-binding proteins(RBPs)and their associated target mRNA was constructed.qRT-PCR was conducted on high glucose(HG)-treated and control HK-2 cells.Our analysis identified a set of 22 hub genes through the intersection of differentially expressed genes(DEGs)with NETs-related genes.Immune infiltration assessments revealed significant differences across 23 immune cell types among the analyzed groups.Hub genes including calcineurin-like phosphoesterase domain-containing 1(CPPED1)showed high diagnostic values(AUC over 0.6).qRT-PCR indicated reduced gene expression levels.In summary,this study identified 22 significantly upregulated DEGs that play a vital role in DN by using gene expression omnibus(GEO)database,GSEA,GSVA,immune infiltration analysis and ROC.The expression levels of CPPED1 may serve as novel diagnostic biomarkers and therapeutic targets.展开更多
The development of electrocatalysts that both work effectively at industrial current density and resist chloride ion(Cl^(-))corrosion remains a key challenge for hydrogen production from Cl^(-)-rich alkaline water.Her...The development of electrocatalysts that both work effectively at industrial current density and resist chloride ion(Cl^(-))corrosion remains a key challenge for hydrogen production from Cl^(-)-rich alkaline water.Herein,we report a CrO_(x)-engineered nickel-based oxide catalyst(FeCoCrO_(x)/NF)that achieves exceptional activity and stability through a dual-functional interfacial mechanism.Combing in situ Raman spectroscopy,18O isotopic labeling,and electrochemical analysis,we demonstrate that the oxygen evolution reaction follows a lattice oxygen-mediated mechanism.The CrO_(x)layer selectively adsorbs hydroxide ions,forming a dynamic interfacial barrier that electrostatically repels Cl^(-)ingress,thereby mitigating Cl^(-)corrosion.Through enthalpy-based analysis,we demonstrate that electronic redistribution via Cr-O-Fe bonding increases the vacancy formation energy of Fe,thereby suppressing its dissolution.In alkaline electrolyte containing 0.5 M Cl^(-)(1.0 M KOH),the catalyst is operating continuously for 1400 h at an industrial current density of 1000 mA cm^(-2).Furthermore,the catalyst retains 99.5%of its initial activity under fluctuating current density(100-1000 mA cm^(-2)),demonstrating robustness required for industrial electrolyzers.This study establishes a paradigm for designing corrosion-resistant electrocatalysts through the synergistic modulation of interfacial ion selectivity and bulk lattice oxygen activation,advancing the application of green hydrogen production in Cl^(-)-rich alkaline water.展开更多
Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamenta...Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamental physics.The^(229)Th ionic nuclear optical clock has garnered considerable attention,attributed to its high precision with a relative uncertainty of≤1.5×10^(-19)and the potential for common-mode noise cancellation via self-comparison between the nuclear transition and the electronic transition of thorium ions.In this article,we focus on Th^(n+)ions(n=1,2,3)and present a comprehensive review of the current progress in the development of ionic nuclear clocks,covering essential steps such as ion generation,trapping,and cooling.Furthermore,we discuss the realization of a closed-loop clock cycle,addressing key aspects including stable isomer excitation and efficient isomer deexcitation.展开更多
文摘Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.
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 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Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions,including phagocytosis,production of reactive oxygen and halogen species,degranulation,and NETosis(formation of neutrophil extracellular traps[NETs]).NETs,which contain antimicrobial compounds such as myeloperoxidase(MPO),represent a strategy to combat infection.However,excessive production of NETs promotes thrombosis,diabetes mellitus,and other diseases.Therefore,investigations into the mechanisms of NETosis and the identification of modulators of this process are critical for developing strategies to address NETosis-related disorders.Here,we identified a novel NETosis inducer,human serum albumin(HSA)modified by the MPO product hypochlorous acid(HSAHOCl),whose accumulation in vivo was correlated with inflammatory processes.Using human blood neutrophils,we investigated HSAHOCl-induced NETosis and detected NET formation by flow cytometry.The results showed that the mechanism of HSAHOClinduced NETosis involved MPO,NADPH oxidase,and phosphatidylinositol 3-kinases(PI3Ks),and that HSAHOCl activated a reactive oxygen species-dependent suicidal type of NETosis.Moreover,HSAHOCl-induced NETosis was inhibited by an anti-HSAHOCl monoclonal antibody.Thus,our findings may facilitate the development of strategies to modulate NETosis in inflammation associated with elevated MPO activity.
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 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 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 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supported by the Natural Science Foundation of Anhui Province in China(2508085MF166)Research Fund of Anhui Institute of Translational Medicine(2024zh-03)+2 种基金Key Scientific Research Foundation of Education Department of Anhui Province(2023AH040083)National Natural Science Foundation of China(12404353)Cultivation Project of Training Young and Middle-aged Teachers in Universities of Anhui Province(DTR2023013).
文摘Optical tweezers technology has the characteristics of noncontact manipulation in three dimensions and steerable separation in solutions,and could be applied to obtain a separated sperm with high quality for intracytoplasmic sperm injection(ICSI).However,the effects of optical tweezers on sperm motility are still unclear.To elucidate the effects on sperm motility for optical tweezers,we systematically investigated the correlation between motility parameters and the parameters of optical tweezers(wavelength,power,trapping duration,and trapping orientation).Under three systems of optical tweezers with different laser wavelengths(1064,850,and 785 nm),the nine motility parameters of free swimming were mainly affected by trapping orientation(vertical/horizontal)and trapping duration.When 850 nm laser and 1064 nm laser are used,vertical trapping significantly reduces sperm free-swimming capability with prolonged exposure time,whereas horizontal trapping exhibits relatively minor interference on sperm motility.Notably,the 785 nm laser does not induce statistically significant changes in key parameters of sperm motility under any experimental conditions(trapping orientation and duration).For the rolling frequency of trapped sperm,horizontal trapping for three wavelengths has a negligible effect compared with vertical trapping,especially for the 785 nm laser.In conclusion,horizontal trapping can preserve sperm motility under low power(below 140mW at 1064 nm,below 100mW at 850nm,below 60mW at 785 nm)and short duration(below 4 min).This trapping duration is suffcient for the separation procedure of single live sperm in ICSI.This study provides critical parameter optimization guidelines for the safe application of optical tweezers technology in reproductive medicine.
基金Supported by the Wenzhou Basic Scientific Research Project(Y2023103)the Basic Public Welfare Research Program of Zhejiang Province(LGD19H070003)。
文摘Diabetic nephropathy(DN)begins with diabetes-related disruptions in glucose metabolism,with oxidative stress playing a crucial role.Neutrophil extracellular traps(NETs)are extensive web-like formations composed of cytosolic and granule proteins,which are dependent on oxidative stress for their formation and function.This study aimed to identify potential targets for DN progression,focusing on NETs,using bioinformatic analysis and quantitative Real-Time PCR(qRT-PCR).We performed differential gene expression(DEG)analysis on two DN-related RNA-seq datasets(GSE142025 and GSE163603)and NETs-related genes.Subsequent analysis included gene set enrichment analysis(GSEA),gene set variation analysis(GSVA),GeneMANIA,and receiver operating characteristic(ROC)curves.Immune cell infiltration levels were assessed via single-sample GSEA,and a regulatory network involving RNA-binding proteins(RBPs)and their associated target mRNA was constructed.qRT-PCR was conducted on high glucose(HG)-treated and control HK-2 cells.Our analysis identified a set of 22 hub genes through the intersection of differentially expressed genes(DEGs)with NETs-related genes.Immune infiltration assessments revealed significant differences across 23 immune cell types among the analyzed groups.Hub genes including calcineurin-like phosphoesterase domain-containing 1(CPPED1)showed high diagnostic values(AUC over 0.6).qRT-PCR indicated reduced gene expression levels.In summary,this study identified 22 significantly upregulated DEGs that play a vital role in DN by using gene expression omnibus(GEO)database,GSEA,GSVA,immune infiltration analysis and ROC.The expression levels of CPPED1 may serve as novel diagnostic biomarkers and therapeutic targets.
基金supported by the National Nature Science Foundation of China under Grant No.22269021the Tianshan Talent Project of Xinjiang Uygur Autonomous Region:2023TSYCQNTJ0039the Open project of Key Laboratory in Xinjiang Uygur Autonomous Region of China:2023D04027。
文摘The development of electrocatalysts that both work effectively at industrial current density and resist chloride ion(Cl^(-))corrosion remains a key challenge for hydrogen production from Cl^(-)-rich alkaline water.Herein,we report a CrO_(x)-engineered nickel-based oxide catalyst(FeCoCrO_(x)/NF)that achieves exceptional activity and stability through a dual-functional interfacial mechanism.Combing in situ Raman spectroscopy,18O isotopic labeling,and electrochemical analysis,we demonstrate that the oxygen evolution reaction follows a lattice oxygen-mediated mechanism.The CrO_(x)layer selectively adsorbs hydroxide ions,forming a dynamic interfacial barrier that electrostatically repels Cl^(-)ingress,thereby mitigating Cl^(-)corrosion.Through enthalpy-based analysis,we demonstrate that electronic redistribution via Cr-O-Fe bonding increases the vacancy formation energy of Fe,thereby suppressing its dissolution.In alkaline electrolyte containing 0.5 M Cl^(-)(1.0 M KOH),the catalyst is operating continuously for 1400 h at an industrial current density of 1000 mA cm^(-2).Furthermore,the catalyst retains 99.5%of its initial activity under fluctuating current density(100-1000 mA cm^(-2)),demonstrating robustness required for industrial electrolyzers.This study establishes a paradigm for designing corrosion-resistant electrocatalysts through the synergistic modulation of interfacial ion selectivity and bulk lattice oxygen activation,advancing the application of green hydrogen production in Cl^(-)-rich alkaline water.
基金Project supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0920000)the National Natural Science Foundation of China(Grant No.12341401)。
文摘Owing to the presence of a low-energy,long-lived nuclear isomeric state,^(229)Th is an ideal candidate for developing the next generation clock—the nuclear clock—holding great promise for both applied and fundamental physics.The^(229)Th ionic nuclear optical clock has garnered considerable attention,attributed to its high precision with a relative uncertainty of≤1.5×10^(-19)and the potential for common-mode noise cancellation via self-comparison between the nuclear transition and the electronic transition of thorium ions.In this article,we focus on Th^(n+)ions(n=1,2,3)and present a comprehensive review of the current progress in the development of ionic nuclear clocks,covering essential steps such as ion generation,trapping,and cooling.Furthermore,we discuss the realization of a closed-loop clock cycle,addressing key aspects including stable isomer excitation and efficient isomer deexcitation.
