BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-neg...BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-negative BC in the ascending colon who underwent laparoscopic radical right hemicolectomy.The patient had undergone left modified radical mastectomy only 15 months ago and stopped chemotherapy just 3 months ago.The diagnosis of CMBC was made based on the previous history of BC and positive results of several specific immunohistochemical markers(gross cystic disease fluid protein 15,mammaglobin,GATA-binding protein 3,and cytokeratin 7)for breast carcinoma.CONCLUSION CMBC should be highly cautious in patients with a previous history of BC,especially triple-negative BC,and further examination to aid in diagnosis.展开更多
The FW2.2-like(FWL)gene family has been extensively studied across multiple species,demonstrating conserved functions among specific members in organ development,particularly in fruit size regulation.For species with ...The FW2.2-like(FWL)gene family has been extensively studied across multiple species,demonstrating conserved functions among specific members in organ development,particularly in fruit size regulation.For species with limited research foundations,such as Chinese jujube,analyzing this gene family is an effective approach to identify candidate genes for fruit size.This study identified twenty ZjFWL genes and comprehensively analyzed their chromosomal distribution,phylogenetic relationships,gene structure,evolutionary dynamics,expression patterns,and cis-acting elements in their promoters.Natural variation analysis of the ZjFWL10 sequence identified a significant correlation between a seven-base pair deletion in the conserved domain and jujube fruit size.To validate the functional implications of the seven-base pair deletion genotype,heterologous overexpression experiments were conducted in tomatoes,generating three overexpression lines.Comparative analysis with the wild-type demonstrated a significant reduction in fruit size and a notable increase in plant height in the overexpressed lines.This gene may play a critical role in regulating nutrient partitioning in jujube,ultimately affecting fruit size.These findings advance our understanding of fruit size regulation mechanisms and offer valuable insights for genetic improvement strategies targeting jujube fruit size.展开更多
By reviewing the development of “three-high” oil and gas well testing technology of Sinopec in recent years, this paper systematically summarizes the application of “three-high” oil and gas well testing technology...By reviewing the development of “three-high” oil and gas well testing technology of Sinopec in recent years, this paper systematically summarizes the application of “three-high” oil and gas well testing technology of Sinopec in engineering optimization design technology, and high temperature and high pressure testing technology, high pressure and high temperature transformation completion integration technology. Major progress has been made in seven aspects: plug removal and re-production technology of production wells in high acid gas fields;wellbore preparation technology of ultra-deep, high-pressure, and high-temperature oil and gas wells;surface metering technology;and supporting tool development technology. This paper comprehensively analyzes the challenges faced by the “three-high” oil and gas well production testing technology in four aspects: downhole tools, production testing technology, safe production testing, and the development of low-cost production test tools. Four development directions are put forward: 1) Improve ultra-deep oil and gas testing technology and strengthen integrated geological engineering research. 2) Deepen oil and gas well integrity evaluation technology to ensure the life cycle of oil and gas wells. 3) Carry out high-end, customized, and intelligent research on oil test tools to promote the low-cost and efficient development of ultra deep reservoirs. 4) Promote the fully automatic control of the surface metering process to realize the safe development of “three-high” reservoirs.展开更多
There are two main trends in the development of unmanned aerial vehicle(UAV)technologies:miniaturization and intellectualization,in which realizing object tracking capabilities for a nano-scale UAV is one of the most ...There are two main trends in the development of unmanned aerial vehicle(UAV)technologies:miniaturization and intellectualization,in which realizing object tracking capabilities for a nano-scale UAV is one of the most challenging problems.In this paper,we present a visual object tracking and servoing control system utilizing a tailor-made 38 g nano-scale quadrotor.A lightweight visual module is integrated to enable object tracking capabilities,and a micro positioning deck is mounted to provide accurate pose estimation.In order to be robust against object appearance variations,a novel object tracking algorithm,denoted by RMCTer,is proposed,which integrates a powerful short-term tracking module and an efficient long-term processing module.In particular,the long-term processing module can provide additional object information and modify the short-term tracking model in a timely manner.Furthermore,a positionbased visual servoing control method is proposed for the quadrotor,where an adaptive tracking controller is designed by leveraging backstepping and adaptive techniques.Stable and accurate object tracking is achieved even under disturbances.Experimental results are presented to demonstrate the high accuracy and stability of the whole tracking system.展开更多
Paper packaging materials like cardboards are widely used to protect archives which are a major kind of cultural relics.Unfortunately,paper is a combustible material,and thus exploring environment-friendly flame retar...Paper packaging materials like cardboards are widely used to protect archives which are a major kind of cultural relics.Unfortunately,paper is a combustible material,and thus exploring environment-friendly flame retardant for paper-based archive packaging material plays an important role.Herein,boric acid,borax and disodium octaborate are used to modify the craft paper-based packaging materials for archive conservation to improve fire safety.The modified craft paper exhibits much higher flame retardancy than the pristine one dose based on vertical burning tests,without much influence on mechanical properties such as tensile strength and elongation at break.Thermogravimetric analysis(TGA),scanning electron microscope(SEM),and X-ray photoelectron spectroscopy(XPS)reveal that porous glass structure is formed during the combustion,because thermal decomposition of boric acid,borax and disodium octaborate will produce porous glassy matter as B_(2)O_(3).The porous glass covers the paper surface as an insulating layer which retards the further pyrolysis and combustion,resulting in a denser carbon layer.Our study provides a robust way to reduce the fire hazard of the archive packaging material by applying environment-friendly boron-based fire retardants.展开更多
Soy protein adhesives are currently a hot research topic in the wood panels industry for the abundant raw material reserves,reasonable price and outstanding environmental features.But their poor water resistance,low b...Soy protein adhesives are currently a hot research topic in the wood panels industry for the abundant raw material reserves,reasonable price and outstanding environmental features.But their poor water resistance,low bonding strength and intolerance to mold are major drawbacks,so that proper modification before use is essential.Glutaraldehyde is one of the more apt cross-linking agents for soybean protein adhesives,which can effectively improve the bonding strength and water resistance of the adhesive.Equally,glutaraldehyde is also an efficient and broad-spectrum fungicide that can significantly improve the anti-fungal properties of a soy protein adhesive.In the work presented here,matrix assisted laser desorption ionization(MALDI-ToF)mass spectrometry and Fourier transform infrared spectroscopy techniques were used to analyze the reaction mechanism of glutaraldehyde cross-linking soybean protein.The results confirmed the reaction of the aldehyde group with amino groups of the side chains and the amide groups of the peptide linkages constituting the skeletal chain of the protein.The laboratory plywood and particleboard bonded with glutaraldehyde-soy bean protein adhesives were prepared to determine the adhesive bonding properties,the dry strength,24 h cold water soaking wet strength and 3 h hot water(63°C)wet strength of plywood were 2.03,1.13 and 0.75 MPa,respectively,which satisfied the requirements of industrial production.展开更多
Abstract Olfactory dysfunction has been reported in Parkinson＇s disease （PD） patients carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the LRRK2 G2385R variant. In this study, we performed g...Abstract Olfactory dysfunction has been reported in Parkinson＇s disease （PD） patients carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the LRRK2 G2385R variant. In this study, we performed genotyping for the LRRK2 G2385R variant in PD patients recruited from the Movement Disorder ClttliC of Xualwu Hospital in Beijing and in healthy controls randomly selected from the Beijing Longitudinal Study on Aging cohort. The ＂five-odor olfactory detection array＂, an olfactory threshold test, was used to assess olfactory function. One hundred and eighty-six participants were enrolled, comprising 43 PD patients without （iPD） and 25 with （LRRK2-PD） the LRRK2 G2385R variant, and 118 healthy controls. Our results showed that the threshold of olfactory identification was significantly worse in PD patients than in controls, but not significantly different between the iPD and LRRK2-PD groups. These findings suggested that although olfactory function in LRRK2-PD patients is impaired, it is similar to that in iPD patients.展开更多
Ladderlike polyhydroxypropylsilsesquioxane (HO-T) was synthesized by alcoholysis of ladderlike poly(3-propionyloxy-propyl)silsesquioxane. The HO-T was characterized by GPC, IR, NMR, DSC, TGA and X-ray diffraction meth...Ladderlike polyhydroxypropylsilsesquioxane (HO-T) was synthesized by alcoholysis of ladderlike poly(3-propionyloxy-propyl)silsesquioxane. The HO-T was characterized by GPC, IR, NMR, DSC, TGA and X-ray diffraction methods. Through hydrogen-bonding interaction, ladderlike polymer (HO-T) can form a supramolecular complex with somewhat regular structure.展开更多
We obtain a new class of polynomial identities on the ring of n × n matrices over any commutative ring with 1 by using the Swan’s graph theoretic method [1] in the proof of Amitsur-Levitzki theorem. Let be an Eu...We obtain a new class of polynomial identities on the ring of n × n matrices over any commutative ring with 1 by using the Swan’s graph theoretic method [1] in the proof of Amitsur-Levitzki theorem. Let be an Eulerian graph with k vertices and d edges. Further let be an integer and assume that . We prore that is an PI on Mn(C). Standard and Chang [2] -Giambruno-Sehgal [3] polynomial identities are the spectial examples of our conclusions.展开更多
In this paper , we have established an intimate connection between near-nings and linear automata,and obtain the following results: 1) For a near-ring N there exists a linear GSA S with N ≌ N(S) iff (a) (N, +) is abe...In this paper , we have established an intimate connection between near-nings and linear automata,and obtain the following results: 1) For a near-ring N there exists a linear GSA S with N ≌ N(S) iff (a) (N, +) is abelian, (b) N has an identity 1, (c) There is some d ∈ Nd such that N0 is generated by {1,d};2) Let h: S → S’ be a GSA- epimorphism. Then there exists a near-ring epimorphism from N(S) to N(S’) with h(qn) = h(q)h(n) for all q ∈ Q and n ∈ N(S);3) Let A = (Q,A,B,F,G) be a GA. Then (a) Aa:=(Q(N(A)) =: Qa,A,B,F/Qa × A) is accessible, (b) Q = 0N(A), (c) A/~:= (Q/~,A,B,F~), Q~) with F^([q], a):= [F(q,a)] and G^([q], a):= G(q,a) is reduced, (d) Aa/~ is minimal.展开更多
Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological...Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological mechanisms.Autophagy refers to an intracellular degrading process with the involvement of lysosomes.Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents.Increasing evidence support that autophagy protects neuronal cells from ischemic injury.However,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain injury.Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke.In the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.展开更多
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 ...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.展开更多
基金The Science and Technology Bureau of Wuhu,Anhui Province,China,Under The Key Research and Development and Achievement Transformation Project,No.2023yf099.
文摘BACKGROUND Breast cancer(BC)metastasis to the gastrointestinal tract is uncommon,colonic metastasis from BC(CMBC)is even rarer.CASE SUMMARY This report describes a 44-year-old female patient with metastatic triple-negative BC in the ascending colon who underwent laparoscopic radical right hemicolectomy.The patient had undergone left modified radical mastectomy only 15 months ago and stopped chemotherapy just 3 months ago.The diagnosis of CMBC was made based on the previous history of BC and positive results of several specific immunohistochemical markers(gross cystic disease fluid protein 15,mammaglobin,GATA-binding protein 3,and cytokeratin 7)for breast carcinoma.CONCLUSION CMBC should be highly cautious in patients with a previous history of BC,especially triple-negative BC,and further examination to aid in diagnosis.
基金supported by the National Natural Science Foundation of China(31800559)the National Key Research and Development Program of China(2022YFD2200404)+2 种基金the National XA Science and Technology Innovation Project,China(2022XACX1100)the Science and Technology Major Project of Guangxi,China(‘Guike’AB16380060)the central government guides local science and technology development project“Germplasm Innovation of Xinjiang Characteristic Fruit Tree”,and partly supported by the open funds of the National Key Laboratory for Germplasm Innovation&Utilization of Horticultural Crops,China.
文摘The FW2.2-like(FWL)gene family has been extensively studied across multiple species,demonstrating conserved functions among specific members in organ development,particularly in fruit size regulation.For species with limited research foundations,such as Chinese jujube,analyzing this gene family is an effective approach to identify candidate genes for fruit size.This study identified twenty ZjFWL genes and comprehensively analyzed their chromosomal distribution,phylogenetic relationships,gene structure,evolutionary dynamics,expression patterns,and cis-acting elements in their promoters.Natural variation analysis of the ZjFWL10 sequence identified a significant correlation between a seven-base pair deletion in the conserved domain and jujube fruit size.To validate the functional implications of the seven-base pair deletion genotype,heterologous overexpression experiments were conducted in tomatoes,generating three overexpression lines.Comparative analysis with the wild-type demonstrated a significant reduction in fruit size and a notable increase in plant height in the overexpressed lines.This gene may play a critical role in regulating nutrient partitioning in jujube,ultimately affecting fruit size.These findings advance our understanding of fruit size regulation mechanisms and offer valuable insights for genetic improvement strategies targeting jujube fruit size.
文摘By reviewing the development of “three-high” oil and gas well testing technology of Sinopec in recent years, this paper systematically summarizes the application of “three-high” oil and gas well testing technology of Sinopec in engineering optimization design technology, and high temperature and high pressure testing technology, high pressure and high temperature transformation completion integration technology. Major progress has been made in seven aspects: plug removal and re-production technology of production wells in high acid gas fields;wellbore preparation technology of ultra-deep, high-pressure, and high-temperature oil and gas wells;surface metering technology;and supporting tool development technology. This paper comprehensively analyzes the challenges faced by the “three-high” oil and gas well production testing technology in four aspects: downhole tools, production testing technology, safe production testing, and the development of low-cost production test tools. Four development directions are put forward: 1) Improve ultra-deep oil and gas testing technology and strengthen integrated geological engineering research. 2) Deepen oil and gas well integrity evaluation technology to ensure the life cycle of oil and gas wells. 3) Carry out high-end, customized, and intelligent research on oil test tools to promote the low-cost and efficient development of ultra deep reservoirs. 4) Promote the fully automatic control of the surface metering process to realize the safe development of “three-high” reservoirs.
基金supported in part by the Institute for Guo Qiang of Tsinghua University(2019GQG1023)in part by Graduate Education and Teaching Reform Project of Tsinghua University(202007J007)+1 种基金in part by National Natural Science Foundation of China(U19B2029,62073028,61803222)in part by the Independent Research Program of Tsinghua University(2018Z05JDX002)。
文摘There are two main trends in the development of unmanned aerial vehicle(UAV)technologies:miniaturization and intellectualization,in which realizing object tracking capabilities for a nano-scale UAV is one of the most challenging problems.In this paper,we present a visual object tracking and servoing control system utilizing a tailor-made 38 g nano-scale quadrotor.A lightweight visual module is integrated to enable object tracking capabilities,and a micro positioning deck is mounted to provide accurate pose estimation.In order to be robust against object appearance variations,a novel object tracking algorithm,denoted by RMCTer,is proposed,which integrates a powerful short-term tracking module and an efficient long-term processing module.In particular,the long-term processing module can provide additional object information and modify the short-term tracking model in a timely manner.Furthermore,a positionbased visual servoing control method is proposed for the quadrotor,where an adaptive tracking controller is designed by leveraging backstepping and adaptive techniques.Stable and accurate object tracking is achieved even under disturbances.Experimental results are presented to demonstrate the high accuracy and stability of the whole tracking system.
文摘Paper packaging materials like cardboards are widely used to protect archives which are a major kind of cultural relics.Unfortunately,paper is a combustible material,and thus exploring environment-friendly flame retardant for paper-based archive packaging material plays an important role.Herein,boric acid,borax and disodium octaborate are used to modify the craft paper-based packaging materials for archive conservation to improve fire safety.The modified craft paper exhibits much higher flame retardancy than the pristine one dose based on vertical burning tests,without much influence on mechanical properties such as tensile strength and elongation at break.Thermogravimetric analysis(TGA),scanning electron microscope(SEM),and X-ray photoelectron spectroscopy(XPS)reveal that porous glass structure is formed during the combustion,because thermal decomposition of boric acid,borax and disodium octaborate will produce porous glassy matter as B_(2)O_(3).The porous glass covers the paper surface as an insulating layer which retards the further pyrolysis and combustion,resulting in a denser carbon layer.Our study provides a robust way to reduce the fire hazard of the archive packaging material by applying environment-friendly boron-based fire retardants.
基金supported by the National Natural Science Foundation of China(31660176)the Yunnan Provincial Natural Science Foundation(202201AU070222)and Scientific Research Fund Project of Yunnan Provincial Department of Education(2022J0490)+1 种基金financed by the ERA-CoBioTech Project WooBAdh(Environmentally-friendly bioadhesives from renewable resources)by the Slovenian Ministry of Education.Science and Sport and the Slovenian Research Agency within the Framework of the Program P4-0015.
文摘Soy protein adhesives are currently a hot research topic in the wood panels industry for the abundant raw material reserves,reasonable price and outstanding environmental features.But their poor water resistance,low bonding strength and intolerance to mold are major drawbacks,so that proper modification before use is essential.Glutaraldehyde is one of the more apt cross-linking agents for soybean protein adhesives,which can effectively improve the bonding strength and water resistance of the adhesive.Equally,glutaraldehyde is also an efficient and broad-spectrum fungicide that can significantly improve the anti-fungal properties of a soy protein adhesive.In the work presented here,matrix assisted laser desorption ionization(MALDI-ToF)mass spectrometry and Fourier transform infrared spectroscopy techniques were used to analyze the reaction mechanism of glutaraldehyde cross-linking soybean protein.The results confirmed the reaction of the aldehyde group with amino groups of the side chains and the amide groups of the peptide linkages constituting the skeletal chain of the protein.The laboratory plywood and particleboard bonded with glutaraldehyde-soy bean protein adhesives were prepared to determine the adhesive bonding properties,the dry strength,24 h cold water soaking wet strength and 3 h hot water(63°C)wet strength of plywood were 2.03,1.13 and 0.75 MPa,respectively,which satisfied the requirements of industrial production.
基金supported by grants from the Scientific Project of Ministry of Science and Technology of China (2012AA02A514)the National Basic Research Development Program of China(2011CB504101)the Beijing High Standard Health Human Resource Cultural Program in Health System,China (2009elel2)
文摘Abstract Olfactory dysfunction has been reported in Parkinson＇s disease （PD） patients carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the LRRK2 G2385R variant. In this study, we performed genotyping for the LRRK2 G2385R variant in PD patients recruited from the Movement Disorder ClttliC of Xualwu Hospital in Beijing and in healthy controls randomly selected from the Beijing Longitudinal Study on Aging cohort. The ＂five-odor olfactory detection array＂, an olfactory threshold test, was used to assess olfactory function. One hundred and eighty-six participants were enrolled, comprising 43 PD patients without （iPD） and 25 with （LRRK2-PD） the LRRK2 G2385R variant, and 118 healthy controls. Our results showed that the threshold of olfactory identification was significantly worse in PD patients than in controls, but not significantly different between the iPD and LRRK2-PD groups. These findings suggested that although olfactory function in LRRK2-PD patients is impaired, it is similar to that in iPD patients.
基金This project is financially supported by National Natural Science Foundation of China (No. 29874034).
文摘Ladderlike polyhydroxypropylsilsesquioxane (HO-T) was synthesized by alcoholysis of ladderlike poly(3-propionyloxy-propyl)silsesquioxane. The HO-T was characterized by GPC, IR, NMR, DSC, TGA and X-ray diffraction methods. Through hydrogen-bonding interaction, ladderlike polymer (HO-T) can form a supramolecular complex with somewhat regular structure.
文摘We obtain a new class of polynomial identities on the ring of n × n matrices over any commutative ring with 1 by using the Swan’s graph theoretic method [1] in the proof of Amitsur-Levitzki theorem. Let be an Eulerian graph with k vertices and d edges. Further let be an integer and assume that . We prore that is an PI on Mn(C). Standard and Chang [2] -Giambruno-Sehgal [3] polynomial identities are the spectial examples of our conclusions.
文摘In this paper , we have established an intimate connection between near-nings and linear automata,and obtain the following results: 1) For a near-ring N there exists a linear GSA S with N ≌ N(S) iff (a) (N, +) is abelian, (b) N has an identity 1, (c) There is some d ∈ Nd such that N0 is generated by {1,d};2) Let h: S → S’ be a GSA- epimorphism. Then there exists a near-ring epimorphism from N(S) to N(S’) with h(qn) = h(q)h(n) for all q ∈ Q and n ∈ N(S);3) Let A = (Q,A,B,F,G) be a GA. Then (a) Aa:=(Q(N(A)) =: Qa,A,B,F/Qa × A) is accessible, (b) Q = 0N(A), (c) A/~:= (Q/~,A,B,F~), Q~) with F^([q], a):= [F(q,a)] and G^([q], a):= G(q,a) is reduced, (d) Aa/~ is minimal.
基金funded by the National Natural Science Foundation of China(81822044,81773703 and 81630098)the Fundamental Research Funds for the Central Universities(2019XZZX004-17,China)
文摘Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological mechanisms.Autophagy refers to an intracellular degrading process with the involvement of lysosomes.Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents.Increasing evidence support that autophagy protects neuronal cells from ischemic injury.However,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain injury.Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke.In the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.
基金National Natural Science Foundation of China,Grant/Award Numbers:82171177,82173076Shanghai Science and Technology Committee Foundation,Grant/Award Number:19ZR1430600+6 种基金Clinical Research Plan of Shanghai Hospital Development Center,Grant/Award Number:SHDC2020CR4062Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai,Grant/Award Number:PWZxq2017-06Shanghai Municipal Key Clinical Specialty,Grant/Award Number:shslczdzk03601Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation,Grant/Award Number:20DZ2254200Shanghai 2021“Science and Technology Innovation Action Plan”domestic science and technology cooperation project,Grant/Award Number:21015801500Innovative research team of high-level local universities in Shanghai,Grant/Award Number:SHSMU-ZLCX20212601STI2030-Major Projects,Grant/Award Number:2022ZD0206200。
文摘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.
