The hurdle technology for food preservation effectively addresses the limitations of individual antimicrobial technologies by integrating their strengths.It can not only prolong the storage time of food but also maint...The hurdle technology for food preservation effectively addresses the limitations of individual antimicrobial technologies by integrating their strengths.It can not only prolong the storage time of food but also maintains its high quality.In this study,three antimicrobial and bactericidal technologies,namely soluble gas stabilization(SGS),modified atmosphere packaging(MAP),and cold plasma(CP),were applied to chilled chicken breasts.The packaging,total viable count(TVC),and physicochemical properties of chilled chicken breasts after treatments and storage at 4℃were monitored.The microbial diversity at the initial and end points of the storage time of each group was also analyzed.The results indicated that a 3−5 h SGS treatment can effectively increase the proportion of carbon dioxide in the MAP during the storage process of chilled chicken breasts,thereby alleviating the packaging collapse problem.Simultaneously,the effect of SGS,MAP,and CP combinational treatments significantly extended the storage time of chilled chicken breasts while maintaining the physicochemical qualities of samples.Compared to the control group,the TVC of chicken breast treated with SGS,MAP,and CP treatments decreased by 0.58(lg(CFU/g))at 0 day.The shelf life was extended by 5 days.After 8 days,the total volatile basic nitrogen(TVB-N)was 26.67 vs.19.50 mg/100 g,thiobarbituric acid reactive substances(TBARS)was 0.99 vs.0.72 mg MDA/kg,and TVC was 8.22 vs.6.52(lg(CFU/g)).High-throughput sequencing results showed that SGS and MAP treatments significantly reduce the proportion of Pseudomonas and Psychrobacter,which are sensitive to carbon dioxide,in the total bacterial genera.This study underscores the potential of integrating multiple antimicrobial technologies for effective food preservation.展开更多
Patients with dense breasts on mammography have a higher risk of developing breast cancer and missing a tumor mass than those with non-dense breasts. Whether examinees who have dense breasts should be notified is curr...Patients with dense breasts on mammography have a higher risk of developing breast cancer and missing a tumor mass than those with non-dense breasts. Whether examinees who have dense breasts should be notified is currently under consideration in Japan;however, there is concern about the low level of understanding regarding dense breasts. A questionnaire survey on the degree of comprehension regarding dense breasts was conducted among 409 general women of >20 years of age in Hachinohe city in October 2017 and 2018. The results showed that the degree of comprehension was extremely low, as only 35 people (8.5%) responded with, “I know the meaning”;however, 32 of them (91.5%) stated that they would like to be notified in they had dense breasts. In addition, the degree of comprehension regarding dense breasts was significantly greater among those who had a breast cancer screening history (OR = 6.4;95% CI = 2.0 - 19.8;P = 0.001) and a self-examination history than among those with no such history (OR = 2.5;95% CI = 1.1 - 5.8;P = 0.03). However, the degree of comprehension did not differ between participants of years of age or between participants with and without a breast cancer sufferer among their close blood relatives. The present findings to reflect a low understanding of dense breasts on mammography screening and suggest that the degree of comprehension is influenced by the presence or absence of a consultation history and a self-examination history.展开更多
Cultural schema theory proposes that when we interact with members of the same culture in certain situations, or talk about certain information with them many times, cultural schemas are created and stored in our brai...Cultural schema theory proposes that when we interact with members of the same culture in certain situations, or talk about certain information with them many times, cultural schemas are created and stored in our brain, which can promote coherence between the original and target language text, thus solving the cultural default caused by the cultural differences. It is vital to make cultural compensation to different cultural schemas and to coordinate the cultural contradiction. This thesis focuses on the translation methods and strategies in Big Breasts and Wide Hips from the perspective of the cultural schema theory, which exemplifies how cultural default and compensation functions in this novel.展开更多
Literary translation has become the most significant pathway for Chinese literature to enter the world literature scene and compete for international recognitions. In order to present a exhaustive analysis and explora...Literary translation has become the most significant pathway for Chinese literature to enter the world literature scene and compete for international recognitions. In order to present a exhaustive analysis and exploration of the strategies of culture translation, it selects one of Mo Yan's classic work Big Breasts and Wide Hips and its English version translated by American scholar Goldblatt as the case study. It will mainly discuss about the cultural transmission through literary translation and the cultivation of talented translators in order to expand Chinese culture's international influence through improving literary translation.展开更多
AIM: To achieve symmetric boundaries for left and right breasts boundaries in thermal images by registration. METHODS: The proposed method for registration consists of two steps. In the first step, shape context, an a...AIM: To achieve symmetric boundaries for left and right breasts boundaries in thermal images by registration. METHODS: The proposed method for registration consists of two steps. In the first step, shape context, an approach as presented by Belongie and Malik was applied for registration of two breast boundaries. The shape context is an approach to measure shape similarity. Two sets of finite sample points from shape contours of two breasts are then presented. Consequently, the correspondences between the two shapes are found. By finding correspondences, the sample point which has the most similar shape context is obtained. RESULTS: In this study, a line up transformation which maps one shape onto the other has been estimated in order to complete shape. The used of a thin plate spline permitted good estimation of a plane transformation which has capability to map unselective points from one shape onto the other. The obtained aligningtransformation of boundaries points has been applied successfully to map the two breasts interior points. Some of advantages for using shape context method in this work are as follows:(1) no special land marks or key points are needed;(2) it is tolerant to all common shape deformation; and(3) although it is uncomplicated and straightforward to use, it gives remarkably powerful descriptor for point sets significantly upgrading point set registration. Results are very promising. The proposed algorithm was implemented for 32 cases. Boundary registration is done perfectly for 28 cases.CONCLUSION: We used shape contexts method that is simple and easy to implement to achieve symmetric boundaries for left and right breasts boundaries in thermal images.展开更多
Introduction: Breast hypertrophy (excessive enlargement of breast), a condition though rare, is well pronounced in some females. Surgery either by reduction mammaplasty or sub-cutaneous mastectomy is often employed in...Introduction: Breast hypertrophy (excessive enlargement of breast), a condition though rare, is well pronounced in some females. Surgery either by reduction mammaplasty or sub-cutaneous mastectomy is often employed in treatment of this condition. Aim: This study seeks to find out the long term level of satisfaction of the surgery on these persons after about 10 - 12 years after treatment. Materials and Methods: From January 1994 to December 2000, the Komfo Anokye Teaching Hospital (KATH) carried out surgeries on 43 females who presented with several degrees of breast hypertrophy. Patients were asked to answer questionnaires on their condition pre-operatively and post-operatively during the long term review process. Results: Thirty-four (79.1%) patients out of the 43 were available for the review with the patients stating there was much (100%) improvement in terms of the pain they felt in the neck, upper and lower back regions. There was no re-occurrence of the condition in any of the patients;29 (85.3%) stated they were satisfied and that their new breast size(s) was/were excellent for them. Conclusion: The pre-operative complications experienced by these patients were resolved hence this surgical procedure was good and the quality of life of these persons had been improved.展开更多
Although a great many qualitative descriptions of the experience of having breast cancer exist, they overwhelmingly represent experiences of women in Western cultures and are based on assumptions that stem from Wester...Although a great many qualitative descriptions of the experience of having breast cancer exist, they overwhelmingly represent experiences of women in Western cultures and are based on assumptions that stem from Western individualism. This study explores and describes cultural models shared by a group of non-Western women, South Koreans, in reference to female breasts and breast cancer. The hermeneutic phenomenology-grounded qualitative study was conducted with 40 Korean women, between 23 and 81 years of age, half of whom were breast cancer survivors. The analysis elicited two cultural models, both characterized in terms of physical relationships to others (as opposed to the woman’s individual or independent view of her body): a breast-feeding mother to a child and an attractive wife to a husband. Female breasts are interpreted as a medium that connects women to roles as mothers and wives. Breast cancer can lead women to detach from their previous relational and role-oriented identities. Cultural traditions, cultural concepts, and culture-related health beliefs in Korea are interwoven deeply in the women’s stories about breasts, as a gendered organ, and its disease. The findings suggest that understanding indigenous cultural models should precede any supportive breast cancer care for women from non-Western cultural backgrounds.展开更多
Objective:We propose a solution that is backed by cloud computing,combines a series of AI neural networks of computer vision;is capable of detecting,highlighting,and locating breast lesions from a live ultrasound vide...Objective:We propose a solution that is backed by cloud computing,combines a series of AI neural networks of computer vision;is capable of detecting,highlighting,and locating breast lesions from a live ultrasound video feed,provides BI-RADS categorizations;and has reliable sensitivity and specificity.Multiple deep-learning models were trained on more than 300,000 breast ultrasound images to achieve object detection and regions of interest classification.The main objective of this study was to determine whether the performance of our Al-powered solution was comparable to that of ultrasound radiologists.Methods:The noninferiority evaluation was conducted by comparing the examination results of the same screening women between our AI-powered solution and ultrasound radiologists with over 10 years of experience.The study lasted for one and a half years and was carried out in the Duanzhou District Women and Children's Hospital,Zhaoqing,China.1,133 females between 20 and 70 years old were selected through convenience sampling.Results:The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value were 93.03%,94.90%,90.71%,92.68%,and 93.48%,respectively.The area under the curve(AUC)for all positives was 0.91569 and the AUC for all negatives was 0.90461.The comparison indicated that the overall performance of the AI system was comparable to that of ultrasound radiologists.Conclusion:This innovative AI-powered ultrasound solution is cost-effective and user-friendly,and could be applied to massive breast cancer screening.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabo...Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.展开更多
The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare I...The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare IoT(H-IoT)technology,which also provides proactive statistical findings and precise medical diagnoses that enhance healthcare performance.This study examines how ML might support IoT-based health care systems,namely in the areas of prognostic systems,disease detection,patient tracking,and healthcare operations control.The study looks at the benefits and drawbacks of several machine learning techniques for H-IoT applications.It also examines the fundamental problems,such as data security and cyberthreats,as well as the high processing demands that these systems face.Alongside this,the essay discusses the advantages of all the technologies,including machine learning,deep learning,and the Internet of Things,as well as the significant difficulties and problems that arise when integrating the technology into healthcare forecasts.展开更多
Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initi...BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.展开更多
BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes...BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.展开更多
Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
大千世界,无奇不有！捷克的选民现在遇到一个难题,基督教民主党在竞选中慷赠免费的喝酒账单,而共产党则让半裸美女在散发竞选印刷品,各施绝招！文章则写得更妙:...forcing people to decide between a free shot and a freepeek！其中...大千世界,无奇不有！捷克的选民现在遇到一个难题,基督教民主党在竞选中慷赠免费的喝酒账单,而共产党则让半裸美女在散发竞选印刷品,各施绝招！文章则写得更妙:...forcing people to decide between a free shot and a freepeek！其中的两个free就值得玩味。文章第二段出现了free shots,这个shots可不能胡乱猜译！《美国传统词典》对shot一词有释:shot:a drink,especially a jigger ofliquor(一杯,尤指一杯酒);an amount to be paid,as for drinks(喝酒的账单),据此,我们可以把free shots译成“免费喝酒的账单”。另外,请勿忘记咀嚼本文的标题！Booze者,酒也;Breasts,美女也。如此搭配,构成了头韵(alliteration)。展开更多
基金supported by the National Natural Science Foundation of China(32272252)the China Agriculture Research System(CARS-41)funded by the Chinese Ministry of Agriculture and Rural Affairs and Wens Fifth Five R&D Major Project(WENS-2020-1-ZDZX-007).
文摘The hurdle technology for food preservation effectively addresses the limitations of individual antimicrobial technologies by integrating their strengths.It can not only prolong the storage time of food but also maintains its high quality.In this study,three antimicrobial and bactericidal technologies,namely soluble gas stabilization(SGS),modified atmosphere packaging(MAP),and cold plasma(CP),were applied to chilled chicken breasts.The packaging,total viable count(TVC),and physicochemical properties of chilled chicken breasts after treatments and storage at 4℃were monitored.The microbial diversity at the initial and end points of the storage time of each group was also analyzed.The results indicated that a 3−5 h SGS treatment can effectively increase the proportion of carbon dioxide in the MAP during the storage process of chilled chicken breasts,thereby alleviating the packaging collapse problem.Simultaneously,the effect of SGS,MAP,and CP combinational treatments significantly extended the storage time of chilled chicken breasts while maintaining the physicochemical qualities of samples.Compared to the control group,the TVC of chicken breast treated with SGS,MAP,and CP treatments decreased by 0.58(lg(CFU/g))at 0 day.The shelf life was extended by 5 days.After 8 days,the total volatile basic nitrogen(TVB-N)was 26.67 vs.19.50 mg/100 g,thiobarbituric acid reactive substances(TBARS)was 0.99 vs.0.72 mg MDA/kg,and TVC was 8.22 vs.6.52(lg(CFU/g)).High-throughput sequencing results showed that SGS and MAP treatments significantly reduce the proportion of Pseudomonas and Psychrobacter,which are sensitive to carbon dioxide,in the total bacterial genera.This study underscores the potential of integrating multiple antimicrobial technologies for effective food preservation.
文摘Patients with dense breasts on mammography have a higher risk of developing breast cancer and missing a tumor mass than those with non-dense breasts. Whether examinees who have dense breasts should be notified is currently under consideration in Japan;however, there is concern about the low level of understanding regarding dense breasts. A questionnaire survey on the degree of comprehension regarding dense breasts was conducted among 409 general women of >20 years of age in Hachinohe city in October 2017 and 2018. The results showed that the degree of comprehension was extremely low, as only 35 people (8.5%) responded with, “I know the meaning”;however, 32 of them (91.5%) stated that they would like to be notified in they had dense breasts. In addition, the degree of comprehension regarding dense breasts was significantly greater among those who had a breast cancer screening history (OR = 6.4;95% CI = 2.0 - 19.8;P = 0.001) and a self-examination history than among those with no such history (OR = 2.5;95% CI = 1.1 - 5.8;P = 0.03). However, the degree of comprehension did not differ between participants of years of age or between participants with and without a breast cancer sufferer among their close blood relatives. The present findings to reflect a low understanding of dense breasts on mammography screening and suggest that the degree of comprehension is influenced by the presence or absence of a consultation history and a self-examination history.
文摘Cultural schema theory proposes that when we interact with members of the same culture in certain situations, or talk about certain information with them many times, cultural schemas are created and stored in our brain, which can promote coherence between the original and target language text, thus solving the cultural default caused by the cultural differences. It is vital to make cultural compensation to different cultural schemas and to coordinate the cultural contradiction. This thesis focuses on the translation methods and strategies in Big Breasts and Wide Hips from the perspective of the cultural schema theory, which exemplifies how cultural default and compensation functions in this novel.
文摘Literary translation has become the most significant pathway for Chinese literature to enter the world literature scene and compete for international recognitions. In order to present a exhaustive analysis and exploration of the strategies of culture translation, it selects one of Mo Yan's classic work Big Breasts and Wide Hips and its English version translated by American scholar Goldblatt as the case study. It will mainly discuss about the cultural transmission through literary translation and the cultivation of talented translators in order to expand Chinese culture's international influence through improving literary translation.
文摘AIM: To achieve symmetric boundaries for left and right breasts boundaries in thermal images by registration. METHODS: The proposed method for registration consists of two steps. In the first step, shape context, an approach as presented by Belongie and Malik was applied for registration of two breast boundaries. The shape context is an approach to measure shape similarity. Two sets of finite sample points from shape contours of two breasts are then presented. Consequently, the correspondences between the two shapes are found. By finding correspondences, the sample point which has the most similar shape context is obtained. RESULTS: In this study, a line up transformation which maps one shape onto the other has been estimated in order to complete shape. The used of a thin plate spline permitted good estimation of a plane transformation which has capability to map unselective points from one shape onto the other. The obtained aligningtransformation of boundaries points has been applied successfully to map the two breasts interior points. Some of advantages for using shape context method in this work are as follows:(1) no special land marks or key points are needed;(2) it is tolerant to all common shape deformation; and(3) although it is uncomplicated and straightforward to use, it gives remarkably powerful descriptor for point sets significantly upgrading point set registration. Results are very promising. The proposed algorithm was implemented for 32 cases. Boundary registration is done perfectly for 28 cases.CONCLUSION: We used shape contexts method that is simple and easy to implement to achieve symmetric boundaries for left and right breasts boundaries in thermal images.
文摘Introduction: Breast hypertrophy (excessive enlargement of breast), a condition though rare, is well pronounced in some females. Surgery either by reduction mammaplasty or sub-cutaneous mastectomy is often employed in treatment of this condition. Aim: This study seeks to find out the long term level of satisfaction of the surgery on these persons after about 10 - 12 years after treatment. Materials and Methods: From January 1994 to December 2000, the Komfo Anokye Teaching Hospital (KATH) carried out surgeries on 43 females who presented with several degrees of breast hypertrophy. Patients were asked to answer questionnaires on their condition pre-operatively and post-operatively during the long term review process. Results: Thirty-four (79.1%) patients out of the 43 were available for the review with the patients stating there was much (100%) improvement in terms of the pain they felt in the neck, upper and lower back regions. There was no re-occurrence of the condition in any of the patients;29 (85.3%) stated they were satisfied and that their new breast size(s) was/were excellent for them. Conclusion: The pre-operative complications experienced by these patients were resolved hence this surgical procedure was good and the quality of life of these persons had been improved.
文摘Although a great many qualitative descriptions of the experience of having breast cancer exist, they overwhelmingly represent experiences of women in Western cultures and are based on assumptions that stem from Western individualism. This study explores and describes cultural models shared by a group of non-Western women, South Koreans, in reference to female breasts and breast cancer. The hermeneutic phenomenology-grounded qualitative study was conducted with 40 Korean women, between 23 and 81 years of age, half of whom were breast cancer survivors. The analysis elicited two cultural models, both characterized in terms of physical relationships to others (as opposed to the woman’s individual or independent view of her body): a breast-feeding mother to a child and an attractive wife to a husband. Female breasts are interpreted as a medium that connects women to roles as mothers and wives. Breast cancer can lead women to detach from their previous relational and role-oriented identities. Cultural traditions, cultural concepts, and culture-related health beliefs in Korea are interwoven deeply in the women’s stories about breasts, as a gendered organ, and its disease. The findings suggest that understanding indigenous cultural models should precede any supportive breast cancer care for women from non-Western cultural backgrounds.
文摘Objective:We propose a solution that is backed by cloud computing,combines a series of AI neural networks of computer vision;is capable of detecting,highlighting,and locating breast lesions from a live ultrasound video feed,provides BI-RADS categorizations;and has reliable sensitivity and specificity.Multiple deep-learning models were trained on more than 300,000 breast ultrasound images to achieve object detection and regions of interest classification.The main objective of this study was to determine whether the performance of our Al-powered solution was comparable to that of ultrasound radiologists.Methods:The noninferiority evaluation was conducted by comparing the examination results of the same screening women between our AI-powered solution and ultrasound radiologists with over 10 years of experience.The study lasted for one and a half years and was carried out in the Duanzhou District Women and Children's Hospital,Zhaoqing,China.1,133 females between 20 and 70 years old were selected through convenience sampling.Results:The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value were 93.03%,94.90%,90.71%,92.68%,and 93.48%,respectively.The area under the curve(AUC)for all positives was 0.91569 and the AUC for all negatives was 0.90461.The comparison indicated that the overall performance of the AI system was comparable to that of ultrasound radiologists.Conclusion:This innovative AI-powered ultrasound solution is cost-effective and user-friendly,and could be applied to massive breast cancer screening.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金funded by Al Jalila Foundation-Research Grant(AJF2023-078)to SSMS.
文摘Objectives:Breast cancer(BC)is the leading cause of cancer-related mortality in women,largely due to metastasis.This study aims to explore the role of purine nucleoside phosphorylase(PNP),a key enzyme in purine metabolism,in the aggressiveness and metastatic behavior of BC.Methods:A comprehensive analysis was performed using in silico transcriptomic data(n=2509 patients),immunohistochemical profiling of BC tissues(n=103),and validation through western blotting in multiple BC cell lines.Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource(TIMER),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and the cBioPortal for cancer genomics(cBioPortal)platforms.Correlations between PNP and key epithelial–mesenchymal transition(EMT)markers,molecular subtypes,tumor grades,and stages were examined.Results:PNP was significantly overexpressed in human epidermal growth factor receptor 2(HER-2)-positive and triple-negative BCs compared to luminal subtypes.High PNP levels were strongly associated with advanced BC stages,high-grade tumors,EMT phenotypes,and poor overall survival.Notably,HER-2 inhibition suppressed PNP expression,while PNP gene silencing induced HER-2 upregulation,revealing a reciprocal regulatory loop.Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.Conclusion:Collectively,PNP emerges as a promising biomarker of BC aggressiveness and progression.Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target.Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.
文摘The integration of machine learning(ML)technology with Internet of Things(IoT)systems produces essential changes in healthcare operations.Healthcare personnel can track patients around the clock thanks to healthcare IoT(H-IoT)technology,which also provides proactive statistical findings and precise medical diagnoses that enhance healthcare performance.This study examines how ML might support IoT-based health care systems,namely in the areas of prognostic systems,disease detection,patient tracking,and healthcare operations control.The study looks at the benefits and drawbacks of several machine learning techniques for H-IoT applications.It also examines the fundamental problems,such as data security and cyberthreats,as well as the high processing demands that these systems face.Alongside this,the essay discusses the advantages of all the technologies,including machine learning,deep learning,and the Internet of Things,as well as the significant difficulties and problems that arise when integrating the technology into healthcare forecasts.
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
基金the Natural Science Foundation of Yongchuan District,No.2023yc-jckx20021.
文摘BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.
文摘BACKGROUNDCancer stem cells(CSCs)drive recurrence and therapeutic resistance in triplenegativebreast cancer(TNBC),a highly aggressive breast cancer subtype.Intratumoralhypoxia,a common feature of solid tumors,promotes CSCs enrichment,yet the mechanisms sustaining CSCs stemness remain poorly understood.Hypoxia-induced reactive oxygen species can oxidatively activate ataxia telangiectasiamutated(ATM)kinase(oxidized ATM,p-ATM)independently of DNA breaks.AIMTo investigate the role of hypoxia-induced oxidized ATM in sustaining TNBCCSCstemness through c-Myc-mediated regulation of one-carbon metabolism.METHODSHs578T and MDA-MB-231 TNBC cells were cultured under normoxia or hypoxia.CSC stemness was assessed by mammosphere assays and flow cytometry.ATMactivity was assessed by pharmacological inhibition(Ku60019)and short hairpinRNA knockdown.c-Myc binding to serine hydroxymethyltransferase 2(SHMT2)and methylenetetrahydrofolate dehydrogenase 2(MTHFD2)promoters was analyzedby dual-luciferase reporter assays and chromatin immunoprecipitation.NADPH/NADP+ratios were quantified,and metabolic reprogramming was profiledby liquid chromatography-tandem mass spectrometry metabolomics.RESULTSHypoxia significantly increased mammosphere formation in both Hs578T and MDA-MB-231 cells,as reflected byhigher numbers of mammospheres(Hs578T:214±18;MDA-MB-231:198±16;both P<0.01)and larger meandiameters(P<0.01).Hypoxia also elevated CD44+/CD24-cell proportions and stemness gene expression(P<0.01).Oxidized ATM was activated under hypoxia withoutγH2AX induction,confirming DNA damage independence.ATM inhibition reduced mammosphere growth and suppressed c-Myc,SHMT2,and MTHFD2.Luciferase and chromatin immunoprecipitation assays confirmed direct c-Myc binding to SHMT2 and MTHFD2promoters,while mutation of the binding sites abolished promoter activity.NADPH/NADP+ratios were significantlyelevated under hypoxia but reduced following ATM inhibition(P<0.05).Metabolomics revealed enrichmentof serine/glycine one-carbon pathways.CONCLUSIONHypoxia-induced oxidized ATM maintains TNBC-CSC stemness by promoting c-Myc-dependent upregulation ofMTHFD2 and SHMT2,linking hypoxia,redox signaling,and one-carbon metabolism.These findings suggest apotential therapeutic axis that could be exploited for TNBC treatment.
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
文摘大千世界,无奇不有！捷克的选民现在遇到一个难题,基督教民主党在竞选中慷赠免费的喝酒账单,而共产党则让半裸美女在散发竞选印刷品,各施绝招！文章则写得更妙:...forcing people to decide between a free shot and a freepeek！其中的两个free就值得玩味。文章第二段出现了free shots,这个shots可不能胡乱猜译！《美国传统词典》对shot一词有释:shot:a drink,especially a jigger ofliquor(一杯,尤指一杯酒);an amount to be paid,as for drinks(喝酒的账单),据此,我们可以把free shots译成“免费喝酒的账单”。另外,请勿忘记咀嚼本文的标题！Booze者,酒也;Breasts,美女也。如此搭配,构成了头韵(alliteration)。
