十堰市社区居民遗体捐献认知度、接受度及意愿度的现状调查

目的了解十堰市社区居民关于遗体捐献的认知度、接受度及意愿度。方法采用便利抽样选取十堰市社区居民共186人实施问卷调查。结果单因素分析结果显示,职业、受教育程度、政治面貌这三个因素在社区居民遗体捐献认知度、接受度、意愿度中均有统计学差异(P<0.05)。结论职业、受教育程度和政治面貌是十堰市社区居民对遗体捐献的认知度、接受度及意愿度的影响因素。

miR-196b-5p促进成肌细胞增殖分化

MicroRNA(miRNA)是一类由内源基因编码的长度约为22个核苷酸的非编码单链RNA分子,在动植物中参与转录后基因表达调控。大量研究表明,miRNA调控骨骼肌的发育,主要表现在肌卫星细胞的激活及增殖、分化、肌管的形成等生物学过程。本实验室前期对大白猪背最长肌(longissimus dorsi,LD)和比目鱼肌(soleus muscle,Sol)进行miRNA测序,筛选鉴定到一个在不同骨骼肌中差异表达并且序列高度保守的miR-196b-5p,目前miR-196b-5p在骨骼肌方面的研究尚未见报道。本研究进一步设计合成miR-196b-5p mimics和inhibitor对C2C12细胞进行miR-196b-5p过表达及干扰表达,利用蛋白免疫印迹、实时荧光定量PCR检测、流式细胞术、免疫荧光染色等方法探究miR-196b-5p对成肌细胞增殖分化的影响,并利用生物信息学预测和双荧光素酶报告系统鉴定了miR-196b-5p的靶基因。结果显示,过表达miR-196b-5p显著增加细胞周期基因Cyclin B、Cyclin D和Cyclin E的mRNA和蛋白表达水平(P<0.05);流式细胞周期检测结果显示,过表达miR-196b-5p显著增加S期细胞比例(P<0.05),表明miR-196b-5p能够加快细胞周期进程;EdU染色结果显示,过表达miR-196b-5p显著促进细胞增殖能力;相反,抑制miR-196b-5p的表达可以显著减弱成肌细胞增殖能力。进一步的功能研究发现,过表达miR-196b-5p能够显著增加成肌标志基因MyoD、MyoG和MyHC的表达水平(P<0.05);MyHC免疫荧光染色结果显示miR-196b-5p可以促进成肌细胞肌管形成,表明miR-196b-5p可以促进成肌细胞分化。生物信息学预测和双荧光素酶实验证明miR-196b-5p可以靶向Sirt1基因,抑制该基因的表达。改变Sirt1表达,不能够挽救miR-196b-5p影响细胞周期的表型,可以减弱miR-196b-5p对成肌细胞分化的促进作用,表明miR-196b-5p通过靶向Sirt1促进成肌细胞分化。

Retinal ganglion cell death in a DBA/2J mouse model of glaucoma Microglial activation and intraocular pressure

BACKGROUND： Retinal microglia has been shown to reactivate in a murine model of pigmentary glaucoma. However, the relationship between microglial activation and intraocular pressure （lOP） elevation and retinal ganglion cell （RGC） death is still unclear. OBJECTIVE： To verify that microglial activation and tumor necrosis factor alpha （TNF-α） expression is involved in RGC death with elevated lOP and prolonged time of glaucomatous optic nerve lesion in a DBA/2J mouse model of glaucoma. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Peking University Third Hospital, Peking University Eye Center, China between December 2006 and May 2008.MATEFIiALS： DBA/2J mice and C57BL/6J mice （Jackson Laboratory, USA）, rat anti-mouse CD11 b monoclonal antibody （Serotec, UK）, and goat anti-TNF-α polyclonal antibody （Sigma, USA） were used in this study.METHODS： A total of 100 female, DBA/2J mice at 3, 6, 9, 12, and 14 months of age （20 mice per age group） were used for the glaucoma model, and 18 C57BL/6J mice at 3, 9, 14 months of age （6 mice per age group） were used as normal controls. The anterior segment of the eye was observed using a slit-lamp biomicroscope, lOP was measured using a microneedle system. Morphology and number of retinal microglia were observed using immunohistochemistry. RGCs were quantified using Nissl staining. Co-localization of TNF-α and microglia was observed using double-labeling immunofluorescence. Excavation of the optic nerve head was observed utilizing hematoxylin-eosin staining. MAIN OUTCOME MEASURES： The following parameters were measured： lOP levels, numbers of RGCs and activated microglia, and TNF-α expression. RESULTS： In 6-month-old DBA/2J mice, dispersed pigment was observed, and some mice developed increased IOP. At 9 months of age, lOP levels reached a peak. In 3-month-old DBA/2J mice, microglia were activated. In 6-month-old DBA/2J mice, the number of activated microglia was significantly increased and migrated to the outer retinal layer. In 9-month-old mice, TNF-a expression was co-localized with microglia. Significant RGC loss occurred in mice aged 9 to 14 months, with the presence of optic nerve fiber loss and optical nerve head excavation, lOP returned to normal levels at 12 months of age, but microglia remained activated, which was consistent with RGC loss. CONCLUSION： Retinal microglial activation was partially attributed to increased lOP. Activated microglia might be mainly responsible for RGC loss. TNF-α expression was evident in the inner retinal layer. However, the relationship between TNF-α and RGC loss remains poorly understood.

A Thermo-Tunable Metamaterial as an Actively Controlled Broadband Absorber

Metamaterials have attracted increasing attention in recent years due to their powerful abilities in manipulating electromagnetic (EM) waves. However, most previously reported metamaterials are unable to actively control full-band EM waves. In this paper, we propose a thermo-tunable broadband metamaterial (T-TBM) using paraffin-based composites (PD-Cs) with different phase transition temperatures. Active control of the T-TBM reflection loss peaks from low to high frequency is realized by manipulating the solid–liquid state of the PD-Cs at different phase transition temperatures. The absorption peak bandwidth (where the reflection loss value is less than −30 dB) can be changed, while the broad bandwidth absorption (where the reflection loss value is less than −10 dB) is satisfied by adjusting the temperature of the T-TBM. It is shown that the stagnation of the phase transition temperature of the PD-Cs in the T-TBM provides a time window for actively controlling the EM wave absorption response under different thermal conditions. The device has a broad application prospect in the fields of EM absorption, intelligent metamaterials, multifunctional structural devices, and more.

Inter-ethnic variation of ocular traits——design and methodology of comparison study among American Caucasians,American Chinese and mainland Chinese

Purpose:To summarize the design and methodology of a multi-center study.With the existed ethnic differences of glaucoma,this survey will explore the differences with regard to anterior and posterior ocular segment parameters between Caucasians and Chinese.Methods:In this study,four cohorts including American Caucasians and American Chinese from San Francisco,southern mainland Chinese from Guangzhou,and northern mainland Chinese from Beijing were prospectively enrolled for a series of eye examinations and tests from May 2008 to December 2010.A total of 120 subjects including 15 of each gender in each age decade from 40s to 70s were recruited for each group.Data of the following tests were collected:a questionnaire eliciting systemic and ocular disease history,blood pressure,presenting and best corrected visual acuity,auto-refraction,Goldmann applanation tonometry,go nioscopy,A-scan,anterior segment optical coherence tomography (ASOCT),ultrasound biomicroscopy (UBM),visual field (VF),Heidel berg retinal tomography (HRT),OCT for optic nerve,and digital fundus photography.Conclusion:this study will provide insights to the etiologies of glaucoma especially PACG through inter-ethnic comparisons of relevant ocular anatomic and functional parameters.

Research capacity and training needs of nurses’in Shanghai,China:A multicenter,cross-sectional survey

Aims:The aim of this study is to investigate nurses’research capacity and related training needs in Shanghai to provide evidence to further nursing research training.Materials and Methods:A cross-sectional design with a convenience sample of 1226 clinical registered nurses,including the Nursing Research Capacity of Self-Evaluation Questionnaire and Research Training Needs Form,was recruited from 14 public hospitals in Shanghai,China.And the influencing factors of nurses’research capacity were analyzed.Results:The mean score of nurses’research capacity was(46.25±22.90)in Shanghai,that was at a low-to-medium level.The influencing factors of nurses’research capacity including age(F=15.983,P<0.001),education(F=20.738,P<0.001),professional title(F=6.993,P=0.001),working years(F=7.803,P<0.001),department(F=8.545,P<0.001),and position(F=−3.354,P=0.001).The most critical factor is the time to participate a study(P<0.001).And what the nurses demanded were writing skills,special lectures,and participating in colleagues’projects mostly.Conclusion:Nurse’s scientific research capacity still needs to be improved in Shanghai.The key to improving this situation is the individualized scientific research training and education for nurses and the practice of more participation in scientific research projects.

MOSS:An Open Conversational Large Language Model

Conversational large language models(LLMs)such as ChatGPT and GPT-4 have recently exhibited remarkable capabilities across various domains,capturing widespread attention from the public.To facilitate this line of research,in this paper,we report the development of MOSS,an open-sourced conversational LLM that contains 16 B parameters and can perform a variety of instructions in multi-turn interactions with humans.The base model of MOSS is pre-trained on large-scale unlabeled English,Chinese,and code data.To optimize the model for dialogue,we generate 1.1 M synthetic conversations based on user prompts collected through our earlier versions of the model API.We then perform preference-aware training on preference data annotated from AI feedback.Evaluation results on real-world use cases and academic benchmarks demonstrate the effectiveness of the proposed approaches.In addition,we present an effective practice to augment MOSS with several external tools.Through the development of MOSS,we have established a complete technical roadmap for large language models from pre-training,supervised fine-tuning to alignment,verifying the feasibility of chatGPT under resource-limited conditions and providing a reference for both the academic and industrial communities.Model weights and code are publicly available at https://github.com/OpenMOSS/MOSS.

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys.Renal fibrosis involves an immune response dominated by macrophages,which activates myofibroblasts in fibrotic niches.However,macrophages exhibit high heterogeneity,hindering their potential as therapeutic cell targets.Herein,we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially.We identified the major profibrotic macrophage subset(Fn1+Spp1+Arg1+)in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK(BIVA-PK)to deplete these cells.BIVA-PK specifically binds to and is internalized by profibrotic macrophages.By inducing macrophage cell death,BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses.The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

Recent progress in co-detection of single-cell transcripts and proteins

Cellular heterogeneity is a universal property of living systems,and the interrogation of single cells facilitates in-depth understanding of distinct cellular states and functions in various biological processes.Co-analysis of transcripts and proteins from the same single cells opens the way to decipher complex RNA regulatory frameworks and phenotypes,facilitating the understanding of cellular fate and function regulations,discovery of novel cell types,and construction of a high-resolution cell atlas.Herein,we review the state-of-art advances in the development of methodologies for co-analysis of single-cell transcripts and proteins.First,imaging-based methods are summarized with particular emphasis on optical and mass spectrometry imaging.Next,sequencing-based approaches for high-throughput and sensitive co-analysis of single-cell transcripts and proteins are described,including droplet-,microwell-,and split-pool-based platforms.Subsequently,combined methods with more flexibility and universality are discussed.These methods commonly employ different strategies or reactions to convert transcripts and proteins of single cells into distinct signals simultaneously,which can be detected by different instruments or platforms.Lastly,some perspectives on the future challenges and development trends in this field are presented.

Single-cell transcriptomic atlas reveals immune and metabolism perturbation of depression in the pathogenesis of breast cancer

Epidemiological evidence indicates that major depressive disorder(MDD)may predispose the development and prognosis of breast cancer(BC)in females[1].However,the mechanisms linking these phenotypes are not fully understood.Chronic stress,a hallmark of depression,has been underscored to affect anti-tumor immunity,tumor metabolic reprogramming,hormone synthesis in BC[2,3],and increase tumor metastasis[4],but there is a lack of detailed cellular-level characterization of how MDD history affects the tumorigenesis of BC.This study explored the single-cell atlas of multiple tissues from BC patients with and without a history of MDD for characterizing the potential molecular alternations in their tumorigenesis(Figure 1A).

基于微流控技术的循环肿瘤细胞分析研究进展

癌症的精准诊疗是提高癌症患者生存率和生存质量的重要手段.液体活检通过采用非侵入采样方式,获取肿瘤病人全面、准确、实时的基因组、转录组及蛋白组等生物学信息,是一种新兴的癌症诊断技术,对癌症精确诊断、个体化治疗、预后评估等方面具有重要意义.循环肿瘤细胞(CTC)是一种从实体瘤组织脱落进入外周血的肿瘤细胞,因能提供完整的细胞生物学信息,是最具应用前景的液体活检靶标.然而, CTC的数量极其稀少、异质性强、所处外周血环境复杂等特点,给CTC的富集和分析带来了巨大的技术挑战.本文将总结本课题组近年来发展的基于CTC液体活检策略,着重讨论在CTC识别、富集与单细胞分析等方面的研究进展.

Yangtze Three Gorges Reservoir, China: A holistic assessment of organic pollution, mutagenic effects of sediments and genotoxic impacts on fish

Besides obvious benefits,the Three Gorges Dam＇s construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir（TGR） ecosystem.In order to record organic contamination,to find links to ecotoxicological impacts and to serve as reference for ensuing monitoring,several sites in the TGR area were screened applying the triad approach with additional lines-of-evidence as a holistic assessment method.Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011 and 2012 to determine organic pollution levels,mutagenic potentials and genotoxic impacts.Two regional hot-spots near the cities of Chongqing and Kaixian were identified and further investigated in 2013.Only polycyclic aromatic hydrocarbons（PAHs） could be detected in sediments in 2011（165-1653 ng/g）,emphasizing their roles as key pollutants of the area.Their ubiquity was confirmed at Chongqing（150-433 ng/g） and Kaixian（127-590 ng/g） in2013.Concentrations were comparable to other major Chinese and German rivers.However,the immense sediment influx suggested a deposition of 216-636 kg PAH/day（0.2-0.6 mg PAH/（m2·day））,indicating an ecotoxicological risk.PAH source analysis highlighted primary impacts of combustion sources on the more industrialized upper TGR section,whereas petrogenic sources dominated the mid-low section.Furthermore,sediment extracts from several sites exhibited significant activities of frameshift promutagens in the Ames fluctuation assay.Additionally,significant genotoxic impairments in erythrocytes of P.vachellii were detected（Chongqing/Kaixian）,demonstrating the relevance of genotoxicity as animportant mode of action in the TGR＇s fish.PAHs,their derivatives and non-target compounds are considered as main causative agents.

The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis

Mesangial proliferative glomerulonephritis(MsPGN)is an inflammatory disease,but both the nature of disease progression and its regulation remain unclear.In the present study,we monitored the course of anti-Thy1 nephritis from days 1 to 5 and established gene expression profiles at each time point using microarrays to explore the development of inflammation.According to the gene expression profiles,macrophage infiltration(triggered by CCL2 activation)was evident on day 1 and enhanced inflammation over the next few days.We screened for genes with expression levels similar to CCL2 and found that the upregulation of the circadian gene albumin D-site-binding protein(DBP)was involved in CCL2 activation in mesangial cells.More importantly,CCL2 expression showed oscillatory changes similar to DBP,and DBP induced peak CCL2 expression at 16:00 a clock on day 1 in the anti-Thy1 nephritis model.We knocked down DBP through transfection with a small interfering RNA(siRNA)and used RNA sequencing to identify the DBP-regulated TNF-α-CCL2 pathway.We performed chromatin immunoprecipitation sequencing(ChIP-Seq)and the dual luciferase assay to show that DBP bound to the TRIM55 promoter,regulating gene expression and in turn controlling the TNF-α-CCL2 pathway.In conclusion,DBP-regulated circadian CCL2 expression by the TRIM55-TNF pathway in injured mesangial cells at an early stage,which promoted macrophage recruitment and in turn triggered infiltration and inflammation in a model of anti-Thy1 nephritis.

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

With the development and introduction of immune checkpoint inhibitors(ICIs)in cancer patients,immune-related side effects have increasingly attracted attention.However,the risks of immune-related renal toxicity are poorly characterized.In this study,we performed a network meta-analysis(NMA)of ICI-related randomized clinical trials(RCTs)to elucidate the comparative risk of acute kidney injury(AKI)in cancer patients receiving different ICIs.We also sought to identify other factors potentially affecting the risk of AKI.PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021.Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data.We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups.We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis.Once significant heterogeneity was detected in a traditional direct meta-analysis,multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI.A total of 85 RCTs were included in this study.In the NMA for the risk of grade 1-5 and 3-5 AKI,ipilimumab showed a significantly higher risk than avelumab and durvalumab,whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab(N1I3)showed a significantly higher risk than other groups.In terms of treatment ranking,durvalumab±low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI,whereas N1I3,ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI.Compared with other cancers,renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI.The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy.In this NMA involving largescale up-to-date ICI trials,we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI.Based on data from the ICI arms of these trials,we also revealed several potential risk factors for immune-related AKI,including tumor type and treatment paradigm.

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.

Roadmap for Additive Manufacturing:Toward Intellectualization and Industrialization

With the rapid development of Additive Manufacturing(AM)technology in the past 30 years,AM has been shift-ing from prototyping to advanced manufacturing of functional components in industry.Intellectualization and industrialization of AM process and equipment could be the bottlenecks to the wide industrial applications of AM technology in the future,which have been highlighted in this paper,aiming at describing the technological research roadmaps for the next 5 to 10 years.According to the data flow in the process and value chains of AM technologies,state-of-art of design methodology,material,process&equipment,smart structures,and ap-plications in extreme scales and environments has been elaborated respectively.Some suggestions on potential challenges for research and development in AM technologies have been provided in each section,which would finally establish a critical technical platform for the future industrial innovation and entrepreneurship.

3D Printing of Continuous Fiber Reinforced Polymer Composites:Development,Application,and Prospective

Continuous fiber reinforced polymer composites(CFRPC)have been widely used in the field of automobile,air-craft,and space due to light weight,high specific strength and modulus in comparison with metal as well as alloys.Innovation on 3D printing of CFRPCs opened a new era for the design and fabrication of complicated composite structure with high performance and low cost.3D printing of CFRPCs provided an enabling technol-ogy to bridge the gaps between advanced materials and innovative structures.State-of-art has been reviewed according to the correlations of materials,structure,process,and performance as well as functions in 3D printing of CFRPCs.Typical applications and future perspective for 3D printing of CFRPCs were illustrated in order to grasp the opportunities and face the challenges,which need much more interdisciplinary researches covering the advanced materials,process and equipment,structural design,and final smart performance.

Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium

Background:Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation.The most important feature of radiation ulcers is progressive ulceration,which results in the expansion of radiation injury to the nonirradiated area and refractory wounds.Current theories cannot explain the progression of radiation ulcers.Cellular senescence refers to as irre-versible growth arrest that occurs after exposure to stress,which contributes to tissue dysfunction by inducing paracrine senescence,stem cell dysfunction and chronic inflammation.However,it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers.Here,we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers.Methods:Radiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for>260 days.The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis,molecular detection and RNA sequencing.Then,the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells(uMSC-CM)were investigated in radiation ulcer models.Results:Radiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers.We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them.Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers.Finally,we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence.Conclusions:Our findings not only characterize the roles of cellular senescence in the progression of radiation ulcers but also indicate the therapeutic potential of senescent cells in their treatment.

Antibody-engineered red blood cell interface for high-performance capture and release of circulating tumor cells

Circulating tumor cells(CTCs),as important liquid biopsy target,can provide valuable information for cancer progress monitoring and individualized treatment.However,current isolation platforms incapable of balancing capture efficiency,specificity,cell viability,and gentle release have restricted the clinical applications of CTCs.Herein,inspired by the structure and functional merits of natural membrane interfaces,we established an antibody-engineered red blood cell(RBC-Ab)affinity interface on microfluidic chip for high-performance isolation and release of CTCs.The lateral fluidity,pliability,and anti-adhesion property of the RBC microfluidic interface enabled efficient CTCs capture(96.5%),high CTCs viability(96.1%),and high CTCs purity(average 4.2-log depletion of leukocytes).More importantly,selective lysis of RBCs by simply changing the salt concentration was utilized to destroy the affinity interface for efficient and gentle release of CTCs without nucleic acid contamination.Using this chip,CTCs were successfully detected in colon cancer samples with 90%sensitivity and 100%specificity(20 patients and 10 healthy individuals).After the release process,KRAS gene mutations of CTCs were identified from all the 5 cancer samples,which was consistent with the results of tissue biopsy.We expect this RBC interface strategy will inspire further biomimetic interface construction for rare cell analysis.

μ-opioid receptor agonist facilitates circulating tumor cell formation in bladder cancer via the MOR/AKT/Slug pathway:a comprehensive study including randomized controlled trial

Background:μ-opioid receptor agonists(MORAs)are indispensable for analgesia in bladder cancer(BC)patients,both during surgery and for chronic pain treatment.Whether MORAs affect BC progression and metastasis remains largely unknown.This study focused on the effects of MORAs on the formation of circulating tumor cells(CTCs)in BC and aimed to provide potential therapeutic targets,which would retain the pain-relieving effects of MORAs in BC patients without sacrificing their long-term prognosis.Methods:Different preclinical models were used to identify the effects of MORAs on the progression of BC.A novel immunocapture microfluidic chip was utilized to analyze whether MORAs affected the number of CTCs in mouse models and clinical BC patients.Bioinformatic analyses,total transcriptome sequencing,and molecular biology methods were then used to investigate the underlying mechanisms in these models and in BC cell lines.Results:Mouse models of hematogenous metastasis and in situ BC demonstrated that tumor metastasis was significantly increased after MORA treatment.A significant increase in the number of mesenchymal and/or epithelial CTCs was detected after MORA treatment in both the mouse models and clinical trial patients.Mechanistically,MORAs facilitated the formation of CTCs by activating the MOR/PI3K/AKT/Slug signaling pathway,hereby promoting the epithelialmesenchymal transition(EMT)of BC cells,as knockdown of MOR,Slug or blockade of PI3K inhibited the EMT process and CTC formation.Conclusion:MORAs promoted BC metastasis by facilitating CTC formation.The EMT-CTC axis could be targeted for preventive measures during MORA treatment to inhibit the associated tumormetastasis or recurrence in BC patients.