Anticancer therapeutic strategies for targeting mutant p53-Y220C

The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.

Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks

Covalent organic frameworks(COFs),a rapidly developing category of crystalline conjugated organic polymers,possess highly ordered structures,large specific surface areas,stable chemical properties,and tunable pore microenvironments.Since the first report of boroxine/boronate ester-linked COFs in 2005,COFs have rapidly gained popularity,showing important application prospects in various fields,such as sensing,catalysis,separation,and energy storage.Among them,COFs-based electrochemical(EC)sensors with upgraded analytical performance are arousing extensive interest.In this review,therefore,we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry,with special emphasis on their usages in the fabrication of chemical sensors,ions sensors,immunosensors,and aptasensors.Notably,the emerged COFs in the electrochemiluminescence(ECL)realm are thoroughly covered along with their preliminary applications.Additionally,final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors,as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

Large-scale interplant exchange of macromolecules between soybean and dodder under nutrient stresses

Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.

A review of ^(17)O isotopic labeling techniques for solid-state NMR structural studies of metal oxides in lithium-ion batteries

Recent advances in utilizing ^(17)O isotopic labeling methods for solid-state nuclear magnetic resonance(NMR)investigations of metal oxides for lithium-ion batteries have yielded extensive insights into their structural and dynamic details.Herein,we commence with a brief introduction to recent research on lithium-ion battery oxide materials studied using ^(17)O solid-state NMR spectroscopy.Then we delve into a review of ^(17)O isotopic labeling methods for tagging oxygen sites in both the bulk and surfaces of metal oxides.At last,the unresolved problems and the future research directions for advancing the ^(17)O labeling technique are discussed.

Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea(Camellia sinensis var.assamica)

Chinese Assam tea(Camellia sinensis var.assamica)is an important tea crop with a long history of cultivation in Yunnan,China.Despite its potential value as a genetic resource,its genetic diversity and domestication/breeding history remain unclear.To address this issue,we genotyped 469 ancient tea plant trees representing 26 C.sinensis var.assamica populations,plus two of its wild relatives(six and three populations of C.taliensis and C.crassicolumna,respectively)using 16 nuclear microsatellite loci.Results showed that Chinese Assam tea has a relatively high,but comparatively lower gene diversity(H_(S)=0.638)than the wild relative C.crassicolumna(H_S=0.658).Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups,with considerable interspecific introgression.The Chinese Assam tea accessions clustered into three gene pools,corresponding well with their geographic distribution.However,New Hybrids analysis indicated that 68.48%of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools.In addition,10%of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C.taliensis.Our results suggest that Chinese Assam tea was domesticated separately in three gene pools(Puer,Lincang and Xishuangbanna)in the Mekong River valley and that the hybrids were subsequently selected during the domestication process.Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex,our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

Asymmetric migration dynamics of the tropical Asian and Australasian floras

The tropical Asian and Australasian floras have a close relationship,and is a vital distribution pattern of seed plants worldwide.As estimated,more than 81 families and 225 genera of seed plants distributed between tropical Asia and Australasia.However,the evolutionary dynamics of two floras were still vague.Here,a total of 29 plant lineages,represented the main clades of seed plants and different habits,were selected to investigate the biotic interchange between tropical Asia and Australasia by integrated dated phylogenies,biogeography,and ancestral state reconstructions.Our statistics indicated that 68 migrations have occurred between tropical Asia and Australasia since the middle Eocene except terminal migrations,and the migration events from tropical Asia to Australasia is more than 2 times of the reverse.Only 12 migrations occurred before 15 Ma,whereas the remaining56 migrations occurred after 15 Ma.Maximal number of potential dispersal events(MDE) analysis also shows obvious asymmetry,with southward migration as the main feature,and indicates the climax of bi-directional migrations occurred after 15 Ma.We speculate that the formation of island chains after the Australian-Sundaland collision and climate changes have driven seed plant migrations since the middle Miocene.Furthermore,biotic dispersal and stable habitat may be crucial for floristic interchange between tropical Asia and Australasia.

Generic classification of Asian horned toads(Anura:Megophryidae: Megophryinae) and monograph of Chinese species

The subfamily Megophryinae,as a representative batrachian group of the Oriental Realm and one of the most diverse groups of amphibians,has attracted considerable attention due to continued conjecture regarding its generic classification and failure to reach a satisfactory consensus.China boasts the richest diversity of Asian horned toads,containing some two thirds of the total species cataloged.However,most species have a complicated taxonomic history,resulting in multiple misidentifications.As such,an overall clarification of historical records and regional checklists is required.In the current investigation,we established the phylogeny of the Asian horned toads and performed detailed examinations with redefinitions of several important morphological traits.Based on the phylogenetic relationships and morphological differences,we propose a new ten-genus classification for the Asian horned toad subfamily Megophryinae:i.e.,Brachytarsophrys,Atympanophrys,Grillitschia,Sarawakiphrys gen.nov.,Jingophrys gen.nov.,Xenophrys,Megophrys,Pelobatrachus,Ophryophryne,and Boulenophrys.Revisions on the diagnosability,distribution,and content of each genus are provided.Furthermore,we present a careful review of the taxonomic history of Asian horned toad species from China and provide a monograph of congeners,including six species of Brachytarsophrys,four species of Atympanophrys,five species of Jingophrys gen.nov.,10 species of Xenophrys,two species of Ophryophryne,and 60 species of Boulenophrys.Finally,we discuss the importance of traditional morphological traits based on multiple populations in taxonomic work as well as taxonomic inflation caused by the genetic species delimitation.

Oncogenic Wnt3a is a promising sensitive biomarker for monitoring hepatocarcinogenesis

Background:The effective treatment for hepatocellular carcinoma(HCC)depends on early diagnosis.Previously,the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation.In this study,we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC.Methods:Sprague-Dawley rats(SD)were fed with diet 2-fluorenylacetamide(2-FAA,0.05%)for inducing hepatocarcinogenesis,and grouped based on liver morphological alteration by Hematoxylin&Eosin(H&E)staining;rats fed with normal chow were used as normal control(NC).Total RNA and protein were purified from rat livers.Differently expressed genes(DEGs)or Wnt3a m RNA,cellular distribution,and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio(SLR log 2 cy5/cy3),immunohistochemistry,and enzyme-linked immunosorbent assay,respectively.Results:Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining.Rats were divided into the cell degeneration(r Deg),precancerosis(r Pre-C)and HCC(r HCC)groups.Total numbers of the up-and down-regulated DEGs with SLR≥8 were 55 and 48 in the r Deg group,268 and 57 in the r Pre-C group,and 312 and 201 in the r HCC group,respectively.Significantly altered genes were involved in cell proliferation,signal transduction,tumor metastasis,and apoptosis.Compared with the NC group,Wnt3a m RNA was increased by 4.6 folds(P<0.001)in the r Deg group,7.4 folds(P<0.001)in the r Pre-C group,and 10.4 folds(P<0.001)in the r HCC group;the positive rates of liver Wnt3a were 66.7%(P=0.001)in the r Deg group,100%(P<0.001)in the r Pre-C group,and 100%(P<0.001)in the r HCC group,respectively.Also,there were significant differences of liver Wnt3a(P<0.001)or serum Wnt3a(P<0.001)among different groups.Conclusions:Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage.

Two New Species of Fire-Bellied Newts (Caudata, Salamandridae, Cynops) from Southeastern China

The fire-bellied newt genus Cynops contains ten known species distributed in China and Japan in East Asia.In this work,two new Cynops species are described,namely Cynops jiaoren sp.nov.distributed in northern Guangdong and Cynops maguae sp.nov.distributed in eastern Jiangxi.The two new species can be distinctly distinguished from their congeners by the independent phylogenetic placements and a combination of morphological characteristics.The discovery of these two new species in the Southeast Chinese Hilly Area,where half of congeners occur,increases the known diversity of Cynops,and indicates unresolved relationships among the species in southeastern China.Further discussions on the taxonomic status of Cynops cyanurus are also provided.

COVID-19 and liver dysfunction in children:Current views and new hypotheses

Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been demonstrated.However,there are few reports and studies on COVID-19 related liver injury in children,and the data are scattered.So that many contradictions have arose.This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient outcomes.Therefore,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak.The etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver injury.In summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.

Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

A highly effective incubation strategy enhanced the urban bird hatch success

Urbanization is currently considered one of the most rapid types of global environmental change.Urban habitats are biotically and abiotically different from their rural areas,i.e.,the ambient temperature,predator,and food availability.These novel challenges create new selection pressures,which allow one to investigate ecoevolutionary responses to contemporary environmental change.A total of 118 breeding nests were monitored for nest predation in both urban and rural areas from 2018 to 2020.We used environmental factors from urban and rural areas and behavioral data from 439 Chinese Blackbird(Turdus mandarinus)valid incubation days to understand the impact of urbanization on the incubation behavior of blackbirds and its adaptation mechanism to the urban environment.Cities have warmer ambient temperatures and lower predation pressures than rural areas.Urban blackbirds chose the incubation strategy with shorter and more bouts,while rural blackbirds selected the incubation strategy with longer and fewer bouts.The plasticity of incubation behavior of urban blackbirds was higher than that of rural areas,and the range of egg temperature was also higher than that of rural areas.In addition,incubation temperature and the number of bouts per day were the key factors affecting the day survival rate of blackbirds,and the hatching rate of urban blackbirds was higher than that of rural blackbirds.Our results provide evidence for behavioral shifts in blackbirds during adaptation to urbanization and support the central role of behavioral adaptation in the successful colonization of new environments by wildlife.These help us understand the behavioral characteristics required for wildlife to live in cities and the urban adaptors faced environmental pressures.

Redefinition of the Odorrana versabilis Group,with a New Species from China(Anura,Ranidae,Odorrana)

Taxonomic studies of the Odorrana versabilis group have been consistently disorganized,and they have often been incorrectly associated with an abandoned subgenus or genus Bamburana in existing literature.In this study,we conducted an integrative taxonomic analysis using molecular phylogenetic analysis of two mitochondrial gene fragments(16S rRNA and CO1)and morphological examination of 41 specimens collected during herpetological surveys in southern China.Our results confirmed the monophyly of O.versabilis group which exhibited distinct morphological traits.We also identified a cryptic lineage sister with O.exiliversabilis.Additionally,our study revealed that O.trankieni was nested within O.nasuta.Consequently,we redefined the morphological characteristics of the O.versabilis group,described a new species in this group,O.confusa sp.nov.,and proposed that O.trankieni be considered a junior synonym of O.nasuta.One of the most significant findings of this study was the observation of distinct morphological changes in adult males across all species within the O.versabilis group between the non-breeding and breeding seasons.This study contributes to research on various aspects of Asian amphibian fauna,including taxonomy,ecology,evolution,and physiology.

In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin

BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients.AIM To evaluate the presence,survival and transmission of different multidrug-resistant bacteria(MDRB)from HCP attire onto skin.METHODS Three MDRB[methicillin-resistant Staphylococcus aureus(MRSA);vancomycin-resistant Enterococcus faecium(VRE);carbapenem-resistant Klebsiella pneumoniae,(CRKP)]were inoculated on textiles from scrubs(60%cotton-40%polyester)and white coat(100%cotton)at concentrations of 108 colony-forming units(CFU),105 CFU,and 103 CFU per mL.The inoculation of swatches was divided in time intervals of 1 min,5 min,15 min,30 min,1 h,2 h,3 h,4 h,5 h,and 6 h.At the end of each period,textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media.Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations,for the whole length of the 6-h experiment.RESULTS MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study.VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h,while showing no growth at 103 CFU/mL.CRKP was recovered from 108 CFU/mL for 6 h,up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL.CONCLUSION Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations.The fact that all MDRB can be sustained and transferred to skin even at lower concentrations,supports that textiles are implicated as vectors of bacterial spread.

Intraspecific scaling and early life history determine the cost of free-flight in a large beetle(Batocera rufomaculata)

The scaling of the energetic cost of locomotion with body mass is well documented at the interspecific level.However,methodological restrictions limit our understanding of the scaling of flight metabolic rate(MR)in free-flying insects.This is particularly true at the intraspecific level,where variation in body mass and flight energetics may have direct consequences for the fitness of an individual.We applied a 13C stable isotope method to investigate the scaling of MR with body mass during free-flight in the beetle Batocera rufomaculata.This species exhibits large intraspecific variation in adult body mass as a consequence of the environmental conditions during larval growth.We show that the flight-MR scales with body mass to the power of 0.57,with smaller conspecifics possessing up to 2.3 fold higher mass-specific flight MR than larger ones.Whereas the scaling exponent of free-flight MR was found to be like that determined for tethered-flight,the energy expenditure during free-flight was more than 2.7 fold higher than for tethered-flight.The metabolic cost of flight should therefore be studied under free-flight conditions,a requirement now enabled by the 13C technique described herein for insect flight.

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

Human-specific insertions play important roles in human phenotypes and diseases.Here we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5.Interestingly,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee divergence.We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques.In addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells.Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene.These findings provide a significant insight into the effects of human-specific insertions on evolution.

Biomolecular basis of the role of diabetes mellitus in osteoporosis and bone fractures

Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.

Effect of an Alien Species Spartina alterniflora Loisel on Biogeochemical Processes of Intertidal Ecosystem in the Jiangsu Coastal Region,China

Spartina alterniflora Loisel，生长在的种内部沿着美国的东方海岸的潮汐的公寓，几乎 30 年以前在中国被介绍并且在中国的沿海的地区由于它的侵略海角成为了一个迫切话题。这相异的种类 S 的影响。alterniflora 在上内部在江苏沿海岸地区的潮汐的生态系统过程被在更早是一座泥公寓的四年的旧 Spartina 盐沼的一座泥公寓和那些比较沉积营养素可获得性和踪迹元素集中特征调查。在每个学习地点，十五个阴谋在不同季节被取样沿着潮汐的公寓决定沉积特征。结果建议有的 Spartina 盐沼沉积更高显著地总计 N，可得到的 P，和含水量，但是比泥公寓沉积降低 pH 和体积密度。沉积咸度，含水量，全部的 N，器官的 C，和可得到的 P 在 Spartina 盐沼沿着一个朝海的方向坡度减少了并且与植被生物资源增加了。而且，尽管这些增加不是重要的，踪迹元素的集中和在沉积的一些金属元素在 Spartina 下面是更高的。在 Spartina 沼泽地，另外，某重金属在沉积的表面层被集中。在这研究的 Spartina 盐沼仅仅是四岁；因此，在江苏沿海岸地区在很长时间框架上推进这相异的种的学习，这被建议应该被执行。

Analgesic,anti-inflammatory and anti-diarrheal activities of ethanolic leaf extract of Typhonium trilobatum L.Schott

Objective:To explore the efficacy of ethanolic leaf extract of Typhonium trilobatum L.Schott in treating diarrhea,pain and inflammation using experimental models.Methods:In the present study,acetic acid-induced writhing,xylene-induced ear edema and castor oil-imluced diarrlieal model were used to evaluate the analgesic,anti-inflammatory and anti-diarrheal activities,respectively.Acute toxicity test was carried out to fix the safe doses of the plant extract.Results:The plant extract demonstrated a significant inhibition of writhing(P<0.01)compared with the control group in acetic acid-induced writhing test in mice.The extract also significantly inhibited the xylene induced ear edema formation(P<0.05).In anti-diarrheal test,the extract significantly decreased the frequency of defecation and increased the mean latent period(P<0.0l)in castor oil-induced diarrheal model mice at the doses of 250 and 500 mg/kg body weight.Conclusions:These results suggest that the extract possesses significant analgesic,anti-inflammatory and anti-diarrheal activities that support to the ethnopharmacologicl uses of this plant.

Involvement of the Mitochondrion-dependent and the Endoplasmic Reticulum Stress-signaling Pathways in Isoliquiritigenin-induced Apoptosis of HeLa Cell

Objective Isoliquiritigenin （ISL）, a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells. Methods Cell viability was evaluated using a 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-tetrazolium bromide （MTT） assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracetlular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5＇, 6, 6＇-tetra-chloro-1, 1＇, 3, 3＇-tetraethyl-imidacarbocyanine iodide （JC-1）. The degradation of poly-ADP-ribose polymerase （PARP） protein, the phosphorylation of PKR-like ER kinase （PERK）, the phosphorylation of the a-subunit of eukaryotic initiation factor 2 （elF2a）, the expression of the 78 kD glucose-regulated protein （GRP 78）, and the activation of caspase-12 were analyzed via western blot analysis. Results ISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum （ER） stress, as indicated by the increase in p-elF2a and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12. Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cel apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.