期刊文献+
共找到7,678篇文章
< 1 2 250 >
每页显示 20 50 100
Mechanisms underlying prostate cancer sensitivity to reactive oxygen species:overcoming radiotherapy resistance and recent clinical advances
1
作者 Meidan Wang Rui Xing +5 位作者 Liqun Wang Mingyue Pan Ruoyun Zhang Ting Li Weiqiang Sun Jing Zhou 《Cancer Biology & Medicine》 2025年第7期747-761,共15页
Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromis... Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients. 展开更多
关键词 Prostate cancer(PCa) radiation therapy(RT) reactive oxygen species(ros) radiotherapy resistance ANTIOXIDANTS
暂未订购
Effects of photo-oxidation and transition metals on the formation of reactive oxygen species from aromatic compounds using spectroscopic method
2
作者 Xiaoyu Hu Juanjuan Qin +5 位作者 Yuanyuan Qin Tianyi Zhao Yuxuan Cao Qinghe Cai Lijia Zhang Yang Zhang 《Journal of Environmental Sciences》 2025年第5期1-11,共11页
Particulate matter(PM)can cause adverse health effects by overproducing reactive oxygen species(ROS).Although the ability of PM to induce ROS generation depends on its composi-tion and environmental factors.This study... Particulate matter(PM)can cause adverse health effects by overproducing reactive oxygen species(ROS).Although the ability of PM to induce ROS generation depends on its composi-tion and environmental factors.This study explores how photo-oxidation affects ROS gen-eration from aromatic compounds(ACs,including catechol(CAT),phthalic acid(PA),and 4,4-oxydibenzoic acid(4,4-OBA))and their mixtures with transition metals(TMs,includ-ing Fe(II),Mn(II),and Cu(II))using Fourier-transform infrared(FTIR)and Ultraviolet-visible spectroscopy(UV-Vis).Results showed that photo-oxidation facilitated ROS generation from ACs.CAT-Fe(II)/Cu(II)showed synergistic effects,but 4,4-OBA-Fe(II)/Cu(II)showed antag-onistic effects.ACs-Mn(II)and PA-Fe(II)/Cu(II)exhibited synergistic effects first and then showed antagonistic effects.The different interactions were due to complexation between ACs and TMs.The photo-oxidized ACs-TMs significantly enhanced ROS generation com-pared with ACs-TMs.The study suggested the photo-oxidation mechanism involved that the transfer ofπ-electrons from the ground to an excited state in benzene rings and func-tional groups,leading to the breakage and formation of chemical bonds or easierπ-electron transfer from ACs to TMs.The former could generate ROS directly or produce polymers that promoted ROS generation,while the latter promoted ROS generation by transferringπ-electrons to dissolved oxygen quickly.Our study revealed that both interactions among components and photo-oxidation significantly influenced ROS generation.Future studies should integrate broader atmospheric factors and PM components to fully assess oxidative potential and health impacts. 展开更多
关键词 reactive oxygen species Aromatic compounds Transitional metals PHOTO-OXIDATION
原文传递
Mogroside V protects against acetaminophen-induced liver injury by reducing reactive oxygen species and c-jun-N-terminal kinase activation in mice
3
作者 Jia-Lin Shi Tian Sun +3 位作者 Qing Li Chun-Mei Li Jun-Fei Jin Chong Zhang 《World Journal of Hepatology》 2025年第3期170-179,共10页
BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the i... BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the impact of MV on acute liver injury(ALI)is unknown.AIM To investigate the hepatoprotective potential of MV against liver damage caused by APAP and to examine the underlying mechanisms.METHODS Mice were divided into three groups:Saline,APAP and APAP+MV.MV(10 mg/kg)was given intraperitoneally one hour before APAP(300 mg/kg)administration.Twenty-four hours after APAP exposure,serum transaminase levels,liver necrotic area,inflammatory responses,nitrotyrosine accumulation,and c-jun-N-terminal kinase(JNK)activation were assessed.Additionally,we analyzed reactive oxygen species(ROS)levels,JNK activation,and cell death in alpha mouse liver 12(AML12)cells.RESULTS MV pre-treatment in vivo led to a reduction in the rise of aspartate transaminase and alanine transaminase levels,mitigated liver damage,decreased nitrotyrosine accumulation,and blocked JNK phosphorylation resulting from APAP exposure,without affecting glutathione production.Similarly,MV diminished the APAP-induced increase in ROS,JNK phosphorylation,and cell death in vitro.CONCLUSION Our study suggests that MV treatment alleviates APAP-induced ALI by reducing ROS and JNK activation. 展开更多
关键词 ACETAMINOPHEN Mogroside V reactive oxygen species Liver injury C-jun-N-terminal kinase
暂未订购
Dibutyl phthalate disrupts[Ca^(2+)]_(i),reactive oxygen species,[pH]_(i),protein kinases and mitochondrial activity,impairing sperm function
4
作者 Seung Hyun Park Myung Chan Gye 《Journal of Environmental Sciences》 2025年第5期68-78,共11页
To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transi... To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility. 展开更多
关键词 Dibutyl phthalate reactive oxygen species(ros) [Ca^(2+)]_(i) [pH]_(i) MITOCHONDRIA Protein kinases SPERM
原文传递
Mechanistic insight on nanomaterial-induced reactive oxygen species formation
5
作者 Jianzhong Cao Qingchun Wu +4 位作者 Xuting Liu Xiangyu Zhu Chunfeng Huang Xinyu Wang Yang Song 《Journal of Environmental Sciences》 2025年第5期200-210,共11页
Reactive oxygen species(ROS)are closely related to cell death,proliferation and inflammation.However,excessive ROS levels may exceed the cellular oxidative capacity and cause irreversible damage.Organisms are often in... Reactive oxygen species(ROS)are closely related to cell death,proliferation and inflammation.However,excessive ROS levels may exceed the cellular oxidative capacity and cause irreversible damage.Organisms are often inadvertently exposed to nanomaterials(NMs).Therefore,elucidating the specific routes of ROS generation induced by NMs is crucial for comprehending the toxicity mechanisms of NMs and regulating their potential applications.This paper provides a comprehensive review of the toxicity mechanisms and applications of NMs from three perspectives:(1)Organelle perspective.Investigating the impact of NMmediated ROS onmitochondria,unravelingmechanisms at the organelle level.(2)NMs’perspective.Exploring the broad applications and biosafety considerations of Nanozymes,a unique class of NMs.(3)Cellular system.Examining the toxic effects and mechanisms of NMs in cells at a holistic cellular level.Expanding on these perspectives,the paper scrutinizes the regulation of Fenton reactions by NMs in organisms.Furthermore,it introduces diseases resulting fromNM-mediated ROS at the organism level.This comprehensive review aims to provide valuable insights for studying NM-mediated mechanisms at both cellular and organism levels,offering considerations for the safe design of nanomaterials. 展开更多
关键词 NANOMATERIALS reactive oxygen species(ros) TOXICITY MITOCHONDRIA Oxidative stress
原文传递
A static magnetic field improves salt tolerance for poplar cuttings by regulating root reactive oxygen species homeostasis
6
作者 Jihuai Hu Wenhao Han +6 位作者 Haojie Zhang Nianzhao Wang Guanqing Wu Qiliang Zhu Fengyun Ma Huimei Tian Yanping Wang 《Journal of Forestry Research》 2025年第5期215-227,共13页
A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is no... A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is not clear how a magnetic field affects metabolism and home-ostasis under stressful conditions such as salinity.In this study,a novel method was developed of a static magnetic field(SMF)to investigate magnetobiological changes in trees.The results show that pre-treatment of poplar(Popu-lus×euramericana‘Neva’)cuttings with a static magnetic field significantly mitigated the negative effects of salinity stress on their growth and physiological activities.Bio-chemical assays revealed that several chemical messengers,including hydrogen peroxide(H2O2)and O_(2)^(·-),were sig-nificantly improved in roots treated with salt,implying an increase reactive oxygen species.A static magnetic field also significantly increased proline concentrations,soluble protein contents,and CAT and SOD activities.Electrophysiological experiments further revealed that pre-treatment with a static magnetic field remarkably decreased salt-induced Na^(+)influx and H^(+)efflux which control plant salt tolerance.In pharmacological experiments,because the Na^(+)/H^(+)cor-relation was closely related to the SMF-activated plasma membrane and Na^(+)antiporter activity alleviated the mas-sive accumulation of salt-induced reactive oxygen spe-cies(ROS)within the roots.In addition,a static magnetic field dramatically increased the transcriptional activity of stress-responsive genes,including PtrRBOHD and PtrHA5.Together,these results indicate that SMF reduced Na^(+)influx by activating Na^(+)/H^(+)antiporters and plasma membrane H^(+)-ATPase to effectively maintain homeostasis by regu-lating the reactive oxygen species system and cytoplasmic osmotic potential.Ultimately,these static magnetic field methods improved salt tolerance in poplar cuttings,and,for future research,similar methods could be applied to other plants. 展开更多
关键词 POPLAR Salt tolerance Static magnetic field Plasma membrane Na^(+)transporters reactive oxygen species(ros)homeostasis
在线阅读 下载PDF
Reactive oxygen species generation by organic materials for efficient photocatalysis
7
作者 Qing Liu Tangxin Xiao +1 位作者 Zhouyu Wang Leyong Wang 《Chinese Chemical Letters》 2025年第10期1-3,共3页
Reactive oxygen species(ROS),including singlet oxygen(^(1)O_(2)),hydroxyl radicals(·OH),and superoxide anions(O_(2)^(·-)),are highly reactive molecules that play central roles in many chemical,biological,and... Reactive oxygen species(ROS),including singlet oxygen(^(1)O_(2)),hydroxyl radicals(·OH),and superoxide anions(O_(2)^(·-)),are highly reactive molecules that play central roles in many chemical,biological,and environmental processes due to their strong oxidative power[1].Generating ROS in a controlled manner under mild conditions is essential for achieving selective oxidation reactions.Light-driven methods are especially appealing for this purpose,as they offer precise control over where and when ROS are produced. 展开更多
关键词 superoxide anions o hydroxyl radicals superoxide anions reactive oxygen species singlet oxygen reactive oxygen species ros including selective oxidation reactionslight driven PHOTOCATALYSIS
原文传递
Tetramethylpyrazine induces reactive oxygen species-based mitochondria-mediated apoptosis in colon cancer cells
8
作者 Yan-Xu Hou Wei Ren +3 位作者 Qing-Qiang He Li-Yan Huang Tian-Hua Gao Hua Li 《World Journal of Gastrointestinal Oncology》 2025年第4期442-450,共9页
BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemo-therapy is a widely used strategy in colon cancer clinical therapy.Chemotherapy resistance is the main cause of recurrence and progres... BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemo-therapy is a widely used strategy in colon cancer clinical therapy.Chemotherapy resistance is the main cause of recurrence and progression in colon cancer.Thus,novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay,and cell apoptosis was assessed by flow cytometry.Apoptosis-associated protein expression was measured using Western blot analysis.Intracellular reactive oxygen species(ROS)levels were assessed by flow cytometry using DCF fluorescence intensity.Xeno-grafts were established by the subcutaneous injection of colon cancer cells into nude mice;tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay.RESULTS TMP induced apoptosis of colon cancer cells via the activation of the mitochon-drial pathway.TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner.CONCLUSION Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS.TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner.The accumu-lation of intracellular ROS is involved in TMP-induced apoptosis.Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer. 展开更多
关键词 TETRAMETHYLPYRAZINE Colon cancer reactive oxygen species APOPTOSIS Cell proliferation
暂未订购
Enhanced reactive oxygen species generation:Synergic process of three-electron oxygen reduction and electrochemical ozone production by bimetallic La-Nb oxides
9
作者 Xiaoge Peng Xu Liu +8 位作者 Xiaosa Wang Yuanan Li Suiqin Li Yuhang Wang Zhikang Bao Haoqiang Cao Yunyi Cao Xing Zhong Jianguo Wang 《Journal of Energy Chemistry》 2025年第5期155-165,共11页
The anodic electrochemical ozone production(EOP)and the cathodic three-electron oxygen reduction reaction(3e^(-)ORR)are effective processes for generating active oxygen species(ROS).However,the activation of ozone(O_(... The anodic electrochemical ozone production(EOP)and the cathodic three-electron oxygen reduction reaction(3e^(-)ORR)are effective processes for generating active oxygen species(ROS).However,the activation of ozone(O_(3))by hydroxyl radical(OH)to form ROS poses significant challenges.The micelle balllike bimetallic La-Nb oxides(LNOx)have been developed as a bifunctional electrocatalyst for both the EOP and 3e^(-)ORR reactions.The LNO20 demonstrated a 9.8%of Faradaic efficiency(FE)in O_(3)production and a transfer number of 2.8 electrons in the 3e^(-)ORR.Theoretical calculations support the notion that the five-membered ring mechanism in LNO20 facilitates O_(3)production.Additionally,the incorporation of La provides active sites that enhance the activation of hydrogen peroxide(^(*)H_(2)O_(2))and the generation of OH.This innovative approach synergistically integrates EOP and 3e^(-)ORR,enhancing the activation of O_(3)to produce ROS,demonstrating exceptional efficacy in the degradation of organic pollutants and antimicrobial activity.The study paves the way for designing advanced electrocatalysts for EOP and 3e^(-)ORR and offers insights into utilizing electrochemical method to support other antibacterial strategies. 展开更多
关键词 Three electron oxygen reduction reaction Electrochemical ozone production Synergistic electrosynthesis reactive oxygen species Antibacterial
在线阅读 下载PDF
Nuclear-targeted reactive oxygen species burst:a self-amplifying nanoplatform that overcomes hypoxia and redox barriers for enhanced sonodynamic cancer therapy
10
作者 Xiaoyuan Wang Meng Li +8 位作者 Rong Cheng Liting Zhao Yanfeng Xi Jianming Wang Peng Gao Lingqian Chang Zixian Liu Di Huang Shengbo Sang 《Bio-Design and Manufacturing》 2025年第5期776-799,I0045-I0055,共35页
Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia a... Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors.This study propose d a novel tumor treatment approach,focusing on ROS-mediated therapy by targ eting the nucleus and depleting glutathione(GSH)levels,which was achieved through a nanoplatform(Pt^(2+)-CDs@PpIX)with integrated functions including GSH detection and depletion,pH-responsive drug release,and nuclear targeting.The Pt^(2+)-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility.Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT,as demonstrated in vitro using Pt^(2+)-CDs@PpIX,which also exhibited significant cellular uptake.Pt^(2+)-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tum or microenvironment models(3 DM-7721).Moreover,in 3 DM-7721 models,hepatoma cells(SMMC-7721)demonstrated significant inhibition of motility,invasion,and colony formation after exposure to Pt^(2+)-CDs@PpIX.Furthermore,intravenous administration of the Pt^(2+)-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting,followed by ultrasound-triggered therapy,without adverse effects in nude mice.Hence,this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs. 展开更多
关键词 Sonodynamic therapy Nuclear targets reactive oxygen species Nanoplatform
暂未订购
Disruption of Energy Metabolism and Reactive Oxygen Species Homeostasis in Honglian Type-Cytoplasmic Male Sterility(HL-CMS)Rice Pollen
11
作者 WANG Mingyue ZHAO Weibo +6 位作者 FENG Xiaoya CHEN Yi LI Junhao FU Jinmei YAN Yingchun CHU Zhaohui HUANG Wenchao 《Rice science》 2025年第1期81-93,I0056-I0058,共16页
Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in m... Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice. 展开更多
关键词 cytoplasmic male sterility POLLEN reactive oxygen species RICE mitochondrial metabolite
在线阅读 下载PDF
Deoxycholic acid induces reactive oxygen species accumulation and promotes colorectal cancer cell apoptosis through the CaMKII-Ca^(2+)pathway
12
作者 Jia-Yan Chen Jing-Yi Wen +6 位作者 Jia-Long Lin Yan Li Yi-Zhang Wu Li-Qin Lou Yong-Liang Lou Zhi-Gui Zuo Xiang Li 《World Journal of Gastrointestinal Oncology》 2025年第8期370-382,共13页
BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHO... BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets. 展开更多
关键词 Deoxycholic acid reactive oxygen species Mitochondrial calcium Apoptosis Colorectal cancer
暂未订购
Unveiling role of Cu(Ⅱ)in photochemical transformation and reactive oxygen species production of schwertmannite in the presence of tartaric acid
13
作者 Xiaokang Hou Huanxin Ma +2 位作者 Mengmeng Zhao Chunhua Feng Shishu Zhu 《Chinese Chemical Letters》 2025年第7期206-211,共6页
Light exposure can accelerate phase transformation of Schwertmannite(Sch)coexisting with lowmolecular-weight organic acids(LMWOAs),affecting the cycling of Fe in acid mine drainage(AMD).However,it is still unclear how... Light exposure can accelerate phase transformation of Schwertmannite(Sch)coexisting with lowmolecular-weight organic acids(LMWOAs),affecting the cycling of Fe in acid mine drainage(AMD).However,it is still unclear how this process relates to the fate of heavy metal contaminants.The study comprehensively reports the significant role and speciation redistribution of Cu(Ⅱ)during the photochemical transformation of a Sch/tartaric acid(TA)system.Based on X-ray diffractometer and Fourier transform infrared spectra results,the presence of TA in simulated AMD significantly promoted photoreductive dissolution and phase transformation of Sch to magnetite(Mt)and goethite(Gt)under anoxic and oxic conditions,respectively.With the addition of 10-30 mg/L Cu(Ⅱ),this transformation of Sch/TA system was significantly inhibited,i.e.,only Gt occurred as product under anoxic conditions and even no phase transformation under oxic conditions.The results of EPR and adsorbed Fe(Ⅱ)indicated that the coexistence of Cu(Ⅱ)suppressed the amount of adsorbed Fe(Ⅱ)available for the transformation of Sch via competitive adsorption with Fe(Ⅱ)and inhibition of ligand-to-metal charge transfer(LMCT)of Sch-TA complexes.Chemical speciation and X-ray photoelectron spectroscopy analysis revealed the proportions of adsorbed and structural Cu(Ⅱ)of Sch/TA system were observably enhanced due to an increase in pH and recrystallization/nucleation growth of newly formed Gt.Under anoxic conditions,62.7%-75.88%of Cu(Ⅱ)was adsorbed on the mineral surface,and during the nucleation and growth of secondary mineral phases,15.49%-17.01%of Cu(Ⅱ)was incorporated into their crystal structure.The changes in distribution of Cu(Ⅱ)further suggested the photochemical transformation of Sch facilitated the sequestration of heavy metals and reduced their bioavailability.These findings enhance the understanding of role and redistribution of Cu(Ⅱ)during the transformation of Sch/LMWOA system in euphotic zone of AMD and provid insights of exploring engineered strategies of AMD remediation. 展开更多
关键词 Acid mine drainage Photochemical transformation reactive oxygen species Heavy metals Ligand-to-metal charge transfer
原文传递
Electrospun polyvinyl alcohol fibres incorporating an antimicrobial gel for enzymatically controlled reactive oxygen species release
14
作者 Joel Yupanqui Mieles Cian Vyas +6 位作者 Evangelos Daskalakis Mohamed Hassan James Birkett Abdalla M.Omar Gavin Humphreys Carl Diver Paulo Bartolo 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2024年第6期899-925,共27页
Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers thera... Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers therapeutic levels of hydrogen peroxide(H_(2)O_(2)),a reactive oxygen species,directly to the wound bed.In this study,electrospinning was used to incorporate RO-101^(■)into a polyvinyl alcohol(PVA)sub-micron fibrous mesh that can act as a delivery agent,achieve a sustained release profile,and provide a barrier against infection.Adequate incorporation of this gel into sub-micron fibres was confirmed via nuclear magnetic resonance spectroscopy.Furthermore,scanning electron microscopy exhibited smooth and uniform meshes with diameters in the 200-500 nm range.PVA/RO-101 electrospun meshes generated H_(2)O_(2) in concentrations exceeding 1 m M/(g·m L)(1 m M=1 mmol/L)after 24 h,and the role of sterilisation on H_(2)O_(2) release was evaluated.PVA/RO-101meshes exhibited antimicrobial activity against both Gram-positive Staphylococcus aureus(S.aureus)and Gram-negative Pseudomonas aeruginosa(P.aeruginosa)bacteria,achieving viable count reductions of up to 1 log unit CFU/mm^(2)(CFU:colony-forming units).Moreover,these meshes were capable of disrupting biofilm formation,even against multidrug-resistant organisms such as methicillin-resistant S.aureus(MRSA).Furthermore,increasing the RO-101^(■)concentration resulted in higher H_(2)O_(2) production and an enhanced antimicrobial effect,while fibroblast cell viability and proliferation tests showed a concentration-dependent response with high cytocompatibility at low RO-101^(■)concentrations.This study therefore demonstrates the potential of highly absorbent PVA/RO-101 meshes as potential antimicrobial wound dressings. 展开更多
关键词 ANTIMICROBIAL ELECTrosPINNING Hydrogen peroxide Polyvinyl alcohol reactive oxygen species Tissue engineering Wound dressing
暂未订购
补中益气汤通过Nrf2/ROS/PERK/CHOP信号通路调控内质网应激改善NSCLC顺铂耐药的分子机制 被引量:1
15
作者 李贺 刘玥彤 +3 位作者 黄婧漪 牟琪瑞 刘春英 高原 《中国实验方剂学杂志》 北大核心 2025年第10期79-89,共11页
目的:探讨补中益气汤通过核因子E2相关因子2(Nrf2)/活性氧(ROS)/双链RNA激活的蛋白激酶R(PKR)样内质网激酶(PERK)/CCAAT增强子结合蛋白同源蛋白(CHOP)信号通路调控内质网应激改善非小细胞肺癌顺铂耐药细胞(A549/DDP)的分子机制。方法:利... 目的:探讨补中益气汤通过核因子E2相关因子2(Nrf2)/活性氧(ROS)/双链RNA激活的蛋白激酶R(PKR)样内质网激酶(PERK)/CCAAT增强子结合蛋白同源蛋白(CHOP)信号通路调控内质网应激改善非小细胞肺癌顺铂耐药细胞(A549/DDP)的分子机制。方法:利用SD大鼠制备空白组、补中益气汤组含药血清,将A549/DDP细胞进行传代处理,并将其随机分为9组,分别为空白组(10%空白大鼠血清培养基)、模型组(10%空白大鼠血清培养基+20 mg·L^(-1)顺铂)、中药组(10%中药组大鼠血清培养基+20 mg·L^(-1)顺铂)、叔丁基对苯二酚(TBHQ)组[10%空白大鼠血清培养基+TBHQ(5μmol·L^(-1))+20 mg·L^(-1)顺铂]、TBHQ+中药组[10%中药组大鼠血清培养基+TBHQ(5μmol·L^(-1))+20 mg·L^(-1)顺铂]、N-乙酰半胱胺酸(NAC)组[10%空白大鼠血清培养基+NAC(600μmol·L^(-1))+20 mg·L^(-1)顺铂]、NAC+中药组[10%中药组大鼠血清培养基+NAC(600μmol·L^(-1))+20 mg·L^(-1)顺铂]、Salubrinal组[10%空白大鼠血清培养基+Salubrinal(20μmol·L^(-1))+20 mg·L^(-1)顺铂]、Salubrinal+中药组[10%中药组大鼠血清培养基+Salubrinal(20μmol·L^(-1))+20 mg·L^(-1)顺铂]。应用细胞增殖与活性检测法(CCK-8)检测各组细胞顺铂的半抑制浓度(IC_(50)),流式细胞术检测ROS水平,透射电镜观察内质网超微结构,蛋白免疫印迹法(Western blot)检测Nrf2、磷酸化(p)-Nrf2、CHOP、p-PERK/PERK、磷酸化真核翻译起始因子2α(p-e IF2α)/e IF2α、活化转录因子4(ATF4),共聚焦荧光定位检测CHOP、p-PERK的荧光表达强度。结果:与模型组比较,中药组能显著降低A549/DDP细胞顺铂的IC_(50)(P<0.01);TBHQ组、NAC组、Salubrinal组可显著升高A549/DDP细胞顺铂的IC_(50)(P<0.01);最佳剂量中药联合TBHQ、NAC、Salubrinal后能在此基础上降低其IC_(50)(P<0.01)。与空白组比较,模型组ROS水平升高(P<0.01);与模型组比较,中药组ROS水平显著升高(P<0.01);TBHQ组、NAC组、Salubrinal组ROS水平均显著降低(P<0.01);而TBHQ、NAC、Salubrinal联合中药使用后,均能明显升高A549/DDP细胞的ROS水平(P<0.01)。空白组中可观察到扁囊状、排列整齐的内质网结构,模型组可观察到内质网轻微扩张,而中药组可观察到明显扩张的内质网,TBHQ组、NAC组、Salubrinal组内质网扩张不明显,而联合中药后,可明显观察到扩张的内质网。CHOP、p-PERK蛋白,相较于空白组,模型组荧光信号强度升高(P<0.01);相较于模型组,中药组荧光信号强度显著升高(P<0.01);TBHQ组、NAC组、Salubrinal组荧光信号强度均低于模型组(P<0.01);TBHQ组、NAC组、Salubrinal组联合中药使用后,较未使用中药组荧光信号强度显著上升(P<0.01)。Nrf2与p-Nrf2蛋白,模型组表达较空白组上升(P<0.05),中药组相关表达较模型组降低(P<0.05),TBHQ组、NAC组、Salubrinal组均较模型组表达上升(P<0.05),联合使用中药后,表达相较于未使用中药组显著下降(P<0.01);PERK与e IF2α蛋白表达量各组间差异无统计学意义;CHOP、p-PERK/PERK、p-e IF2α/e IF2α、ATF4蛋白,模型组表达较空白组升高(P<0.05),中药组表达较模型组明显升高(P<0.05),TBHQ组、NAC组、Salubrinal组表达量均低于模型组(P<0.05),TBHQ组、NAC组、Salubrinal组联合中药使用后,较未使用中药组表达量显著上升(P<0.01)。结论:补中益气汤通过Nrf2/ROS/PERK/CHOP信号通路调控内质网应激改善非小细胞肺癌顺铂耐药。 展开更多
关键词 补中益气汤 非小细胞肺癌 化疗耐药 内质网应激 活性氧
原文传递
昆虫ROS免疫防御机制及在寿命调控中的作用
16
作者 马振刚 陈胜 +2 位作者 张俊 黄廷悦 周泽扬 《昆虫学报》 北大核心 2025年第7期1007-1022,共16页
活性氧(reactive oxygen species,ROS)是一类由于氧分子不完全氧化而形成的含氧自由基或容易形成氧自由基的过氧化物的总称。当昆虫受到病原入侵时,由双氧化酶(dual oxidase,DUOX)介导的ROS防御系统会迅速反应,产生大量的ROS以抵御病原... 活性氧(reactive oxygen species,ROS)是一类由于氧分子不完全氧化而形成的含氧自由基或容易形成氧自由基的过氧化物的总称。当昆虫受到病原入侵时,由双氧化酶(dual oxidase,DUOX)介导的ROS防御系统会迅速反应,产生大量的ROS以抵御病原菌的入侵,进而在调控昆虫免疫防御过程中发挥作用;但高水平的ROS会破坏细胞内的蛋白质、DNA、脂质等生物大分子,从而导致昆虫细胞损伤,影响昆虫正常发育。为了避免受到过度氧化应激的损害,昆虫已经形成了一整套以抗氧化酶和小分子抗氧化剂为主体的抗氧化防御系统来避免过度损伤的发生。有趣的是,细胞中ROS水平的改变还能够在昆虫寿命调控中发挥截然不同的作用:对某些昆虫中大量ROS的积累可导致寿命缩短,而对于另外一些昆虫高生理水平的ROS存在又可诱导滞育的发生进而延长其寿命。近年来,ROS在昆虫寿命调控机制方面的研究取得了较多的进展。因此,本文全面地综述了昆虫ROS的来源与产生的影响因素、ROS介导的防御机制,并首次对ROS在昆虫寿命调控中的具体作用进行了总结与展望,以期为后续开展ROS相关主题的研究提供参考。 展开更多
关键词 昆虫 活性氧 免疫防御 寿命 滞育
在线阅读 下载PDF
基于Nrf2/ROS通路探讨补中益气汤调控内质网应激改善非小细胞肺癌的顺铂耐药性
17
作者 于丹 牟琪瑞 +3 位作者 李贺 刘玥彤 黄婧漪 高原 《中国实验方剂学杂志》 北大核心 2025年第10期98-104,共7页
目的:通过观察补中益气汤通过核因子E_(2)相关因子2(Nrf2)/活性氧(ROS)通路对人肺腺癌细胞(A549)、人肺腺癌顺铂耐药细胞(A549/DDP)内质网应激相关分子的影响,探讨补中益气汤改善非小细胞肺癌顺铂耐药的机制。方法:制备补中益气汤含药... 目的:通过观察补中益气汤通过核因子E_(2)相关因子2(Nrf2)/活性氧(ROS)通路对人肺腺癌细胞(A549)、人肺腺癌顺铂耐药细胞(A549/DDP)内质网应激相关分子的影响,探讨补中益气汤改善非小细胞肺癌顺铂耐药的机制。方法:制备补中益气汤含药血清并培养A549细胞、A549/DDP细胞,随机分组为A组(A549细胞+空白血清)、B组(A549细胞+20 mg·L^(-1)顺铂+空白血清)、C组(A549细胞+20 mg·L^(-1)顺铂+10%补中益气汤含药血清)、D组(A549/DDP细胞+空白血清)、E组(A549/DDP细胞+20 mg·L^(-1)顺铂+空白血清)、F组(A549/DDP细胞+20 mg·L^(-1)顺铂+10%补中益气汤含药血清),应用细胞增殖与活性检测法(CCK-8)检测各组细胞顺铂半数抑制浓度(IC_(50)),蛋白免疫印迹法(Western blot)检测各组细胞Nrf2、磷酸化(p)-Nrf2蛋白表达量,DCFH-DA荧光探针法检测各组活性氧(ROS)含量,Western blot检测各组细胞葡萄糖调节蛋白78(GRP78)、活化转录因子6(ATF6)、转录因子C/EBP同源蛋白(CHOP)的蛋白表达量。结果:与A549顺铂组比较,A549补中益气汤组可明显降低细胞对顺铂的IC_(50)(P<0.05),与A549/DDP顺铂组比较,A549/DDP补中益气汤组亦可显著降低细胞对顺铂的IC_(50)(P<0.05),且与A549细胞比较,A549/DDP细胞的IC_(50)在补中益气汤干预前后均高于A549细胞(P<0.05)。与A组比较,B组的Nrf2、p-Nrf2蛋白表达量明显上调(P<0.05),与B组比较,C组的Nrf2、p-Nrf2蛋白表达量则明显下调(P<0.05);与D组比较,E组的Nrf2、p-Nrf2蛋白表达显著上调(P<0.05),与E组比较,F组的Nrf2、p-Nrf2蛋白表达显著下调(P<0.05);与A组比较,B组和C组的细胞ROS表达明显上调,其中C组表达量更高(P<0.05),与D组比较,E组和F组的细胞ROS表达量均明显上调,其中F组表达更高(P<0.05),且两株细胞比较,顺铂和补中益气汤干预前后,A549细胞的ROS表达量均要明显高于A549/DDP细胞(P<0.05)。与A组比较,B组和C组的GRP78、ATF6、CHOP蛋白表达均显著上调,且C组表达更高(P<0.05),与D组比较,E组和F组的GRP78、ATF6、CHOP蛋白表达均显著上调,且F组的表达更高(P<0.05),在两株细胞间比较,A549细胞GRP78、ATF6、CHOP的表达要明显高于A549/DDP细胞(P<0.05)。结论:补中益气汤可能通过Nrf2/ROS通路调控内质网应激改善非小细胞肺癌的顺铂耐药。 展开更多
关键词 补中益气汤 非小细胞肺癌 核因子E2相关因子2(Nrf2)/活性氧(ros) 内质网应激 顺铂耐药
原文传递
巨细胞病毒感染通过促进ROS/NLRP3介导的炎症小体激活引起心肌细胞损伤
18
作者 王好 庞吉 +1 位作者 李帼瑞 钱海 《病毒学报》 北大核心 2025年第3期806-812,共7页
巨细胞病毒(Cytomegalovirus,CMV)感染可引起心肌细胞损伤,但相关机制尚不清楚。CMV感染引起神经元损伤与激活活性氧(ROS)/Nod样受体蛋白3(NLRP3)炎症小体途径有关。为分析ROS/NLRP3介导的炎症小体激活在MCMV感染致心肌细胞损伤中的作用... 巨细胞病毒(Cytomegalovirus,CMV)感染可引起心肌细胞损伤,但相关机制尚不清楚。CMV感染引起神经元损伤与激活活性氧(ROS)/Nod样受体蛋白3(NLRP3)炎症小体途径有关。为分析ROS/NLRP3介导的炎症小体激活在MCMV感染致心肌细胞损伤中的作用,本研究以乳鼠原代心肌细胞为研究对象,对照组用无药物和病毒的培养基进行处理,MCMV组单独感染CMV,N-乙酰半胱氨酸(N-acetylcysteine,NAC)组用含有NAC的培养基进行处理,MCMV+NAC组使用MCMV感染并用含有NAC的培养基进行处理。处理24h后,检测细胞活力与凋亡率,检测培养基中乳酸脱氢酶(LDH)、磷酸肌酸激酶同工酶(CK-MB)、白细胞介素(IL)-1β、IL-18与肿瘤坏死因子-α(TNF-α)的含量,检测细胞中NLRP3、ASC、Caspase-1与Caspase-3的mRNA转录水平及GSDMD-N蛋白表达水平。结果显示,MCMV组细胞活力低于对照组;凋亡率,培养基中LDH、CK-MB、IL-1β、IL-18与TNF-α含量,细胞中NLRP3、ASC、Caspase-1与Caspase-3的mRNA转录水平及GSDMD-N的蛋白表达水平均高于对照组(P<0.05)。MCMV+NAC组细胞活力高于MCMV组、低于NAC组;凋亡率,培养基中LDH、CK-MB、IL-1β、IL-18与TNF-α含量,细胞中NLRP3、ASC、Caspase-1与Caspase-3的mRNA转录水平及GSDMD-N的蛋白表达水平均低于MCMV组、高于NAC组(P<0.05)。上述结果表明,CMV感染引起心肌细胞损伤,这一损伤作用与激活ROS/NLRP3介导的炎症小体有关。 展开更多
关键词 巨细胞病毒 活性氧 Nod样受体蛋白3 炎症小体
原文传递
SKI通过ROS/JNK通路诱导铁死亡干预胰腺癌恶性行为
19
作者 秦瑞峰 薛佳栋 +4 位作者 张佳 刘帆 张绍辉 尹立阳 袁增江 《昆明医科大学学报》 2025年第10期44-52,共9页
目的探讨紫草素(shikonin,SKI)能否通过ROS/JNK通路诱导铁死亡从而抑制胰腺癌恶性行为。方法选用人胰腺癌PANC-1细胞或BxPC-3细胞,药效实验设置空白组(Con组)、SKI低、中、高剂量组(2,4,8μmol/L),JNK相关机制实验分为空白组(Con组)、SK... 目的探讨紫草素(shikonin,SKI)能否通过ROS/JNK通路诱导铁死亡从而抑制胰腺癌恶性行为。方法选用人胰腺癌PANC-1细胞或BxPC-3细胞,药效实验设置空白组(Con组)、SKI低、中、高剂量组(2,4,8μmol/L),JNK相关机制实验分为空白组(Con组)、SKI组(SKI组)、SKI+JNK抑制剂组(SKI+SP600125组),ROS相关机制实验分为空白组(Con组)、SKI组(SKI组)、SKI+ROS清除剂组(SKI+NAC组)。采用CCK-8法检测细胞活力并计算半数抑制浓度(IC50);Transwell实验评估细胞迁移与侵袭能力;使用C11 BODIPY 581/591探针通过流式细胞术检测脂质过氧化水平,FerroOrange荧光探针测定亚铁离子水平;活性氧检测试剂盒检测ROS水平;Western blot法检测铁死亡关键蛋白(SLC7A11、GPX4)、凋亡相关蛋白(Caspase3、PARP)及JNK通路蛋白(JNK、p-JNK)的表达;采用体内异种移植瘤模型检测体内肿瘤增殖情况。结果SKI处理可浓度依赖性和时间依赖性地显著抑制PANC-1细胞(IC50为6.04μmol/L,P<0.0001)和BxPC-3细胞(IC50为12.27μmol/L,P<0.0001)活力,并明显减少迁移和侵袭的细胞数(P<0.0001),8μmol/L SKI处理组迁移细胞数降至对照组的约30%(P<0.0001)。机制上,SKI诱导细胞内脂质过氧化水平升高、Fe2+积累以及ROS大量生成(P<0.0001),同时显著下调SLC7A11和GPX4的蛋白表达(GPX4蛋白表达降至对照组的40%,P<0.0001),并激活JNK磷酸化(p-JNK/JNK比值增至2.8倍,P<0.0001)。而使用JNK特异性抑制剂SP600125或ROS清除剂NAC预处理,均能有效逆转SKI对细胞活力的抑制或对SLC7A11/GPX4蛋白的下调作用(均P<0.01)。SKI也能在体内抑制胰腺癌肿瘤细胞的增殖(P<0.0001)。结论SKI通过激活ROS/JNK通路诱导铁死亡,进而抑制胰腺癌增殖、迁移与侵袭。 展开更多
关键词 紫草素 铁死亡 胰腺癌 活性氧 JNK
暂未订购
铁死亡抑制剂通过调控PI3K/AKT/ROS信号通路减轻心肌细胞凋亡的实验研究
20
作者 龙骁 陈然 +2 位作者 杨涛 黄玉艳 汤长春 《中西医结合心脑血管病杂志》 2025年第15期2307-2312,共6页
目的:探讨铁死亡抑制剂(Fer-1)通过活性氧(ROS)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路抑制心血管疾病中心肌细胞凋亡的作用机制。方法:将大鼠H9c2心肌细胞随机分为对照组、缺氧/复氧(H/R)组、H/R+磷酸缓冲盐溶液(PBS)组、H/R+... 目的:探讨铁死亡抑制剂(Fer-1)通过活性氧(ROS)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路抑制心血管疾病中心肌细胞凋亡的作用机制。方法:将大鼠H9c2心肌细胞随机分为对照组、缺氧/复氧(H/R)组、H/R+磷酸缓冲盐溶液(PBS)组、H/R+Fer-1低剂量组、H/R+Fer-1中剂量组、H/R+Fer-1高剂量组。H/R组、H/R+PBS组、H/R+Fer-1低剂量组、H/R+Fer-1中剂量组、H/R+Fer-1高剂量组在H9c2细胞进行H/R诱导,测定乳酸脱氢酶(LDH)、氧化应激和胞内铁离子Fe^(2+)水平。蛋白免疫印迹法检测铁死亡标志物谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合酶4(ACSL4)水平,H/R诱导的H9c2细胞用1、3、12μmol/L浓度的Fer-1处理培养,检测细胞活力,采用实时荧光定量聚合酶链式反应和蛋白免疫印迹法检测PI3K/AKT信号通路的表达。结果:H/R诱导的H9c2细胞活力降低,氧化应激和乳酸脱氢酶含量增加,Fe^(2+)和ACSL4水平升高,GPX4水平降低。Fer-1抑制H/R诱导的心肌细胞铁死亡和氧化应激。PI3K/AKT信号通路在H/R诱导的H9c2细胞中的表达降低,而Fer-1处理后可升高其表达,差异均有统计学意义(P<0.05)。结论:Fer-1通过激活ROS/PI3K/AKT信号通路来减弱H/R诱导的心肌细胞铁死亡。 展开更多
关键词 心肌细胞凋亡 铁死亡 活性氧 磷脂酰肌醇3-激酶 蛋白激酶B 实验研究
暂未订购
上一页 1 2 250 下一页 到第
使用帮助 返回顶部