Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and...Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.展开更多
Boundary effect and time-reversal symmetry are hot topics in active matter. We present a biology-inspired robotenvironment-interaction active matter system with the field-drive motion and the rules of resource search,...Boundary effect and time-reversal symmetry are hot topics in active matter. We present a biology-inspired robotenvironment-interaction active matter system with the field-drive motion and the rules of resource search, resource consumption, and resource recovery. In an environmental compression–expansion cycle, the swarm emerges a series of boundary-dependent phase transitions, and the whole evolution process is time-reversal symmetry-breaking;we call this phenomenon “orderly hysteresis”. We present the influence of the environmental recovery rate on the dynamic collective behavior of the swarm.展开更多
<div style="text-align:justify;"> Water is the key factor to ensure plant survival in the process of ecological restoration in the coal base of China northwest deserts. On the premise of meeting the mi...<div style="text-align:justify;"> Water is the key factor to ensure plant survival in the process of ecological restoration in the coal base of China northwest deserts. On the premise of meeting the mine production and living water demands, we should take measures such as dirt wastewater treatment and water-saving irrigation to increase income and reduce expenditure and allocate limited water re-sources rationally, to provide mining area ecological restoration maximum usable water resources. The mining dump has large slope and thin soil layer and it is easy to produce surface runoff. So it is particularly important to study the irrigation technology needed to satisfy vegetation restoration, on the premise of guaranteeing not to produce surface runoff and the slope stability. In this paper, through field plot test, the suitable irrigation method for mine slope, slope surface soil moisture migration characteristics and slope stability analysis were studied. Results show that three slope ir-rigation technologies have their own advantages and disadvantages. On the whole, the effect of drip irrigation is the best, micro spray irrigation is the second, infiltrating irrigation is not ideal. The permeability of mine soil slope is very strong, the infiltration rate of the slope direction is the high-est, inverse slope infiltration rate is lowest. In the process of irrigation, with the increase of soil moisture content, slope safety factor is the decreased obviously, the whole slope surface soil moisture content is 14% for the slope stability safety threshold. </div>展开更多
Wheat straw biodegradability during anaerobic digestion was improved by treatment with potassium hydroxide(KOH)to decrease digestion time and enhance biomethane production and fertility value.KOH concentrations of1%(K...Wheat straw biodegradability during anaerobic digestion was improved by treatment with potassium hydroxide(KOH)to decrease digestion time and enhance biomethane production and fertility value.KOH concentrations of1%(K1),3%(K2),6%(K3)and 9%(K4)were tested for wheat straw pretreatment at ambient temperature with a C:N ratio of 25:1.86% of total solids(TS),89% of volatile solids(VS)and 22% of lignocellulose,cellulose and hemicellulose(LCH)(22%)were decomposed effectively with the wheat straw pretreated by 6% KOH.Enhanced biogas production and cumulative biomethane yield of 258 ml·(g VS)^(-1)were obtained increased by 45% and 41%respectively,compared with untreated wheat straw.Pretreated wheat straw digestion also yielded a digestate with higher fertilizer values potassium(138%),calcium(22%)and magnesium(16%).These results show that TS,VS and LCH can be effectively removed from wheat straw pretreated with KOH,improving biodegradability biomethane production and fertilizer value.展开更多
With a large number of researches being conducted on two?dimen?sional(2D) materials, their unique properties in optics, electrics, mechanics, and magnetics have attracted increasing attention. Accordingly, the idea of...With a large number of researches being conducted on two?dimen?sional(2D) materials, their unique properties in optics, electrics, mechanics, and magnetics have attracted increasing attention. Accordingly, the idea of combining distinct functional 2D materials into heterostructures naturally emerged that pro?vides unprecedented platforms for exploring new physics that are not accessible in a single 2D material or 3D heterostructures. Along with the rapid development of controllable, scalable, and programmed synthesis techniques of high?quality 2D heterostructures, various heterostructure devices with extraordinary performance have been designed and fabricated, including tunneling transistors, photodetectors, and spintronic devices. In this review, we present a summary of the latest progresses in fabrications, properties, and applications of di erent types of 2D heterostruc?tures, followed by the discussions on present challenges and perspectives of further investigations.展开更多
Spintronics,exploiting the spin degree of electrons as the information vector,is an attractive field for implementing the beyond Complemetary metal-oxide-semiconductor(CMOS)devices.Recently,two-dimensional(2D)material...Spintronics,exploiting the spin degree of electrons as the information vector,is an attractive field for implementing the beyond Complemetary metal-oxide-semiconductor(CMOS)devices.Recently,two-dimensional(2D)materials have been drawing tremendous attention in spintronics owing to their distinctive spin-dependent properties,such as the ultralong spin relaxation time of graphene and the spin-valley locking of transition metal dichalcogenides.Moreover,the related heterostructures provide an unprecedented probability of combining the di erent characteristics via proximity e ect,which could remedy the limitation of individual 2D materials.Hence,the proximity engineering has been growing extremely fast and has made significant achievements in the spin injection and manipulation.Nevertheless,there are still challenges toward practical application;for example,the mechanism of spin relaxation in 2D materials is unclear,and the high-effciency spin gating is not yet achieved.In this review,we focus on 2D materials and related heterostructures to systematically summarize the progress of the spin injection,transport,manipulation,and application for information storage and processing.We also highlight the current challenges and future perspectives on the studies of spintronic devices based on 2D materials.展开更多
Fluorescence lifetime imaging microscopy(FLIM)has been rapidly developed over the past 30 years and widely applied in biomedical engineering.Recent progress in fluorophore-dyed probe design has widened the application...Fluorescence lifetime imaging microscopy(FLIM)has been rapidly developed over the past 30 years and widely applied in biomedical engineering.Recent progress in fluorophore-dyed probe design has widened the application prospects of fluorescence.Because fluorescence lifetime is sensitive to microenvironments and molecule alterations,FLIM is promising for the detection of pathological conditions.Current cancer-related FLIM applications can be divided into three main categories:(i)FLIM with autofluorescence molecules in or out of a cell,especially with reduced form of nicotinamide adenine dinucleotide,and flavin adenine dinucleotide for cellular metabolism research;(ii)FLIM with Förster resonance energy transfer for monitoring protein interactions;and(iii)FLIM with fluorophore-dyed probes for specific aberration detection.Advancements in nanomaterial production and efficient calculation systems,as well as novel cancer biomarker discoveries,have promoted FLIM optimization,offering more opportunities for medical research and applications to cancer diagnosis and treatment monitoring.This review summarizes cutting-edge researches from 2015 to 2020 on cancer-related FLIM applications and the potential of FLIM for future cancer diagnosis methods and anti-cancer therapy development.We also highlight current challenges and provide perspectives for further investigation.展开更多
Cancer cell motility and its heterogeneity play an important role in metastasis, which is responsible for death of 90% of cancer patients. Here, in combination with a microfluidic technique, single-cell tracking, and ...Cancer cell motility and its heterogeneity play an important role in metastasis, which is responsible for death of 90% of cancer patients. Here, in combination with a microfluidic technique, single-cell tracking, and systematic motility analysis,we present a rapid and quantitative approach to judge the motility heterogeneity of breast cancer cells MDA-MB-231 and MCF-7 in a well-defined three-dimensional(3D) microenvironment with controllable conditions. Following this approach,identification of highly mobile active cells in a medium with epithelial growth factor will provide a practical tool for cell invasion and metastasis investigation of multiple cancer cell types, including primary cells. Further, this approach could potentially become a speedy(~ hours) and efficient tool for basic and clinical diagnosis.展开更多
Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facili...Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates,indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells.However,the effect of anisotropy on cell migration dynamics,in particular,in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission,has not been systematically investigated.In this work,we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function,both qualitatively and quantitatively.Secondly,we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles,especially the nonlinear decrease and non-monotonic behaviors.We particularly elaborate and discuss the mechanisms,and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells.Finally,we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics,and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters.Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.展开更多
The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including...The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including cell-to-cell,cell-to-chemical material,cell-to-environment interaction,etc.In this study,we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro,while constructed a three-dimensional(3D)biochip to simulate a micro-environment for the growth and invasion of spheroids.In the experiment,the 3D spheroid was implanted into the chip,and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion.The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment,namely obvious invasive branches appeared on the spheroids within 24 hours.In order to analyze this interesting phenomenon,we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell.The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells.This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms,but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.展开更多
The in vivo tumor microenvironment is a complex niche that includes heterogeneous physical structures,unique biochemical gradients and multiple cell interactions.Its high-fidelity in vitro reconstruction is of fundame...The in vivo tumor microenvironment is a complex niche that includes heterogeneous physical structures,unique biochemical gradients and multiple cell interactions.Its high-fidelity in vitro reconstruction is of fundamental importance to improve current understandings of cell behavior,efficacy predictions and drug safety.In this study,we have developed a high-throughput biochip with hundreds of composite extracellular matrix(ECM)microchambers to co-culture invasive breast cancer cells(MDA-MB-231-RFP)and normal breast epithelial cells(MCF-10 A-GFP).The composite ECM is composed of type I collagen and Matrigel which provides a heterogeneous microenvironment that is similar to that of in vivo cell growth.Additionally,the growth factors and drug gradients that involve human epidermal growth factor(EGF),discoidin domain receptor 1(DDR1)inhibitor 7 rh and matrix metalloproteinase inhibitor batimastat allow for the mimicking of the complex in vivo biochemical microenvironment to investigate their effect on the spatial-temporal dynamics of cell growth.Our results demonstrate that the MDA-MB-231-RFP cells and MCF-10 A-GFP cells exhibit different spatial proliferation behaviors under the combination of growth factors and drugs.Basing on the experimental data,we have also developed a cellular automata(CA)model that incorporated drug diffusion to describe the experimental phenomenon,as well as employed Shannon entropy(SE)to explore the effect of the drug diffusion coefficient on the spatial-temporal dynamics of cell growth.The results indicate that the uniform cell growth is related to the drug diffusion coefficient,which reveals that the pore size of the ECM plays a key role in the formation of complex biochemical gradients.Therefore,our integrated,biomimetic and high-throughput co-culture platforms,as well as the computational model can be used as an effective tool for investigating cancer pathogenesis and drug development.展开更多
Computational models of eye-movement control during reading provide precise quantitative descriptions of the perceptual, cognitive, and motoric processing that guide readers′ eyes, but are based on numerous equivocal...Computational models of eye-movement control during reading provide precise quantitative descriptions of the perceptual, cognitive, and motoric processing that guide readers′ eyes, but are based on numerous equivocal a priori theoretical assumptions. This article describes an alternative approach to understanding eye-movement control: Using reinforcement learning to examine how complex eye-movement behaviors emerge from the requirement to identify words rapidly in the context of known psychological and physiological constraints(e.g., limited visual acuity). An example simulation is reported, as are key results from an fMRI experiment that demonstrates that structures implicated in reinforcement learning support the learning of eye-movement behavior in humans.展开更多
The purpose of rural informationization is to provide effective information for farmers,increase production efficiency and income level of farmers in agricultural production.In recent years,under the guidance of No.1 ...The purpose of rural informationization is to provide effective information for farmers,increase production efficiency and income level of farmers in agricultural production.In recent years,under the guidance of No.1 document of central government,China's rural informationization has obtained considerable development.However,due to influence of terrain,mountain areas are still backward in informationization development.Combining actual conditions of Pingshan County of Hebei Province,the authors visited local farmers and made detailed survey on basic conditions of farmers,and analyzed factors obstructing agricultural informationization development in mountain areas,to provide theoretical reference for promoting informationization development in mountain areas and increasing income of local farmers.展开更多
Community facilities accidents happen every year in many cities of China, which has been an important issue in academic circles. The purpose of this study is to suggest the direction of universal design for the preven...Community facilities accidents happen every year in many cities of China, which has been an important issue in academic circles. The purpose of this study is to suggest the direction of universal design for the prevention of community facilities accidents. In this paper, from the overall angle, the impact factors of the urban community service facilities safety were analyzed. Then, based on the integrated governance theory, from such aspects as engineering and non-engineering disaster reduction, the governance measures were explored.展开更多
Objective:To investigate the potential value of PDT(photodynamic therapy)in the treatment of rectal cancer by reviewing the diagnosis and treatment process of a patient with advanced rectal cancer who lost the opportu...Objective:To investigate the potential value of PDT(photodynamic therapy)in the treatment of rectal cancer by reviewing the diagnosis and treatment process of a patient with advanced rectal cancer who lost the opportunity of surgery.Methods:Select the case data of a patient receiving photodynamic therapy in our hospital,and analyze the photodynamic mechanism safety and efficiency,and discuss the efficacy of photodynamic therapy.Results:After the patient received photodynamic therapy,re-examination of the endoscopy showed that the intestinal cavity was smoother than before,the bowel was difficult,and the symptoms of blood in the stool improved.Conclusion:Photodynamic therapy can be used as a radical or palliative treatment for clinical tumor treatment.Because of its advantages of minimally invasive,tissue-specific,repetitive and synergistic radiotherapy and chemotherapy,it plays an important role in early or middle-advanced colorectal cancer and is worthy of clinical promotion.展开更多
基金support from the National Natural Science Foundation of China(Grant Nos.11974066,12174041,12104134,T2350007,and 12347178)the Fundamental and Advanced Research Program of Chongqing(Grant No.cstc2019jcyj-msxm X0477)+3 种基金the Natural Science Foundation of Chongqing(Grant No.CSTB2022NSCQMSX1260)the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202301333)the Scientific Research Fund of Chongqing University of Arts and Sciences(Grant Nos.R2023HH03 and P2022HH05)College Students’Innovation and Entrepreneurship Training Program of Chongqing Municipal(Grant No.S202310642002)。
文摘Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 11974066 and 12174041)the Seed Grants from the Wenzhou Institute, University of Chinese Academy of Sciences (Grant No. WIUCASQD2021002)。
文摘Boundary effect and time-reversal symmetry are hot topics in active matter. We present a biology-inspired robotenvironment-interaction active matter system with the field-drive motion and the rules of resource search, resource consumption, and resource recovery. In an environmental compression–expansion cycle, the swarm emerges a series of boundary-dependent phase transitions, and the whole evolution process is time-reversal symmetry-breaking;we call this phenomenon “orderly hysteresis”. We present the influence of the environmental recovery rate on the dynamic collective behavior of the swarm.
文摘<div style="text-align:justify;"> Water is the key factor to ensure plant survival in the process of ecological restoration in the coal base of China northwest deserts. On the premise of meeting the mine production and living water demands, we should take measures such as dirt wastewater treatment and water-saving irrigation to increase income and reduce expenditure and allocate limited water re-sources rationally, to provide mining area ecological restoration maximum usable water resources. The mining dump has large slope and thin soil layer and it is easy to produce surface runoff. So it is particularly important to study the irrigation technology needed to satisfy vegetation restoration, on the premise of guaranteeing not to produce surface runoff and the slope stability. In this paper, through field plot test, the suitable irrigation method for mine slope, slope surface soil moisture migration characteristics and slope stability analysis were studied. Results show that three slope ir-rigation technologies have their own advantages and disadvantages. On the whole, the effect of drip irrigation is the best, micro spray irrigation is the second, infiltrating irrigation is not ideal. The permeability of mine soil slope is very strong, the infiltration rate of the slope direction is the high-est, inverse slope infiltration rate is lowest. In the process of irrigation, with the increase of soil moisture content, slope safety factor is the decreased obviously, the whole slope surface soil moisture content is 14% for the slope stability safety threshold. </div>
基金Supported by Specialized Research Fund for the Doctoral Program of Higer Education(20120010110004)the Natural Science Foundation of Beijing(8142030)
文摘Wheat straw biodegradability during anaerobic digestion was improved by treatment with potassium hydroxide(KOH)to decrease digestion time and enhance biomethane production and fertility value.KOH concentrations of1%(K1),3%(K2),6%(K3)and 9%(K4)were tested for wheat straw pretreatment at ambient temperature with a C:N ratio of 25:1.86% of total solids(TS),89% of volatile solids(VS)and 22% of lignocellulose,cellulose and hemicellulose(LCH)(22%)were decomposed effectively with the wheat straw pretreated by 6% KOH.Enhanced biogas production and cumulative biomethane yield of 258 ml·(g VS)^(-1)were obtained increased by 45% and 41%respectively,compared with untreated wheat straw.Pretreated wheat straw digestion also yielded a digestate with higher fertilizer values potassium(138%),calcium(22%)and magnesium(16%).These results show that TS,VS and LCH can be effectively removed from wheat straw pretreated with KOH,improving biodegradability biomethane production and fertilizer value.
基金supported by NSF of China (Grant No. 61775241)partly by the Innovation-driven Project (Grant No. 2017CX019)the funding support from the Australian Research Council (ARC Discovery Projects, DP180102976)
文摘With a large number of researches being conducted on two?dimen?sional(2D) materials, their unique properties in optics, electrics, mechanics, and magnetics have attracted increasing attention. Accordingly, the idea of combining distinct functional 2D materials into heterostructures naturally emerged that pro?vides unprecedented platforms for exploring new physics that are not accessible in a single 2D material or 3D heterostructures. Along with the rapid development of controllable, scalable, and programmed synthesis techniques of high?quality 2D heterostructures, various heterostructure devices with extraordinary performance have been designed and fabricated, including tunneling transistors, photodetectors, and spintronic devices. In this review, we present a summary of the latest progresses in fabrications, properties, and applications of di erent types of 2D heterostruc?tures, followed by the discussions on present challenges and perspectives of further investigations.
基金partially supported by the National Natural Science Foundation of China(Grant No.61775241)the Youth Innovation Team(Grant No:2019012)of CSU+3 种基金the Hunan province key research and development project(Grant No:2019GK2233)Hunan Province Graduate Research and Innovation Project(Grant No:CX20190177)the Science and Technology Innovation Basic Research Project of Shenzhen(Grant No.JCYJ20180307151237242)the funding support from the Australian Research Council(ARC Discovery Project,DP180102976).
文摘Spintronics,exploiting the spin degree of electrons as the information vector,is an attractive field for implementing the beyond Complemetary metal-oxide-semiconductor(CMOS)devices.Recently,two-dimensional(2D)materials have been drawing tremendous attention in spintronics owing to their distinctive spin-dependent properties,such as the ultralong spin relaxation time of graphene and the spin-valley locking of transition metal dichalcogenides.Moreover,the related heterostructures provide an unprecedented probability of combining the di erent characteristics via proximity e ect,which could remedy the limitation of individual 2D materials.Hence,the proximity engineering has been growing extremely fast and has made significant achievements in the spin injection and manipulation.Nevertheless,there are still challenges toward practical application;for example,the mechanism of spin relaxation in 2D materials is unclear,and the high-effciency spin gating is not yet achieved.In this review,we focus on 2D materials and related heterostructures to systematically summarize the progress of the spin injection,transport,manipulation,and application for information storage and processing.We also highlight the current challenges and future perspectives on the studies of spintronic devices based on 2D materials.
基金This work was partially supported by the National Natural Science Foundation of China(Grant No.61775241)the Hunan Science Fund for Distinguished Young Scholar(2020JJ2059)+3 种基金Youth Innovation Team(Grant No.2019012)of CSU,Hunan province key research and development project(Grant No.2019GK2233,Grant 2020SK2053)Hunan Province Graduate Research and Innovation Project(Grant No.CX20190177)the Science and Technology Innovation Basic Research Project of Shenzhen(Grant No.JCYJ20180307151237242)Also,YPL acknowledges the support by the Project of State Key Laboratory of High-Performance Complex Manufacturing,Central South University(Grant No.ZZYJKT2020-12).Besides,we acknowledge the art work from Servier Medical Art.Y.Z.O and Y.P.L contributed equally to this work.
文摘Fluorescence lifetime imaging microscopy(FLIM)has been rapidly developed over the past 30 years and widely applied in biomedical engineering.Recent progress in fluorophore-dyed probe design has widened the application prospects of fluorescence.Because fluorescence lifetime is sensitive to microenvironments and molecule alterations,FLIM is promising for the detection of pathological conditions.Current cancer-related FLIM applications can be divided into three main categories:(i)FLIM with autofluorescence molecules in or out of a cell,especially with reduced form of nicotinamide adenine dinucleotide,and flavin adenine dinucleotide for cellular metabolism research;(ii)FLIM with Förster resonance energy transfer for monitoring protein interactions;and(iii)FLIM with fluorophore-dyed probes for specific aberration detection.Advancements in nanomaterial production and efficient calculation systems,as well as novel cancer biomarker discoveries,have promoted FLIM optimization,offering more opportunities for medical research and applications to cancer diagnosis and treatment monitoring.This review summarizes cutting-edge researches from 2015 to 2020 on cancer-related FLIM applications and the potential of FLIM for future cancer diagnosis methods and anti-cancer therapy development.We also highlight current challenges and provide perspectives for further investigation.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11674043 and 11604030)the Fundamental Research Funds for the Central Universities,China(Grant No.2018CDJDWL0011)+1 种基金the Fundamental and Advanced Research Program of Chongqing,China(Grant No.cstc2018jcyjAX0338)Arizona State University Start-up Funds,USA
文摘Cancer cell motility and its heterogeneity play an important role in metastasis, which is responsible for death of 90% of cancer patients. Here, in combination with a microfluidic technique, single-cell tracking, and systematic motility analysis,we present a rapid and quantitative approach to judge the motility heterogeneity of breast cancer cells MDA-MB-231 and MCF-7 in a well-defined three-dimensional(3D) microenvironment with controllable conditions. Following this approach,identification of highly mobile active cells in a medium with epithelial growth factor will provide a practical tool for cell invasion and metastasis investigation of multiple cancer cell types, including primary cells. Further, this approach could potentially become a speedy(~ hours) and efficient tool for basic and clinical diagnosis.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974066,11674043,11675134,and 11874310)the Natural Science Foundation of Chongqing,China(Grant Nos.cstc2019jcyj-msxmX0477 and cstc2018jcyjA3679)the Capital Health Development Research Project,China(Grant No.2020-2-2072).
文摘Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates,indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells.However,the effect of anisotropy on cell migration dynamics,in particular,in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission,has not been systematically investigated.In this work,we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function,both qualitatively and quantitatively.Secondly,we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles,especially the nonlinear decrease and non-monotonic behaviors.We particularly elaborate and discuss the mechanisms,and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells.Finally,we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics,and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters.Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974066 and 11674043)the Fundamental Research Funds for the Central Universities,China(Grant No.2019CDYGYB007)the Natural Science Foundation of Chongqing,China(Grant No.cstc2019jcyj-msxmX0477).
文摘The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including cell-to-cell,cell-to-chemical material,cell-to-environment interaction,etc.In this study,we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro,while constructed a three-dimensional(3D)biochip to simulate a micro-environment for the growth and invasion of spheroids.In the experiment,the 3D spheroid was implanted into the chip,and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion.The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment,namely obvious invasive branches appeared on the spheroids within 24 hours.In order to analyze this interesting phenomenon,we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell.The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells.This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms,but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.
基金supported by the National Natural Science Foundation of China(Grant Nos.11974066 and 12174041)the Fundamental and Advanced Research Program of Chongqing,China(Grant No.cstc2019jcyj-msxmX0477)+2 种基金the Capital Health Development Research Project(Grant No.2020-22072)the Key Specialized Research and Development Breakthrough of Henan Province,China(Grant No.212102310887)the Key Scientific Research Projects of Colleges and Universities of Henan Province,China(Grant No.21A416005)。
文摘The in vivo tumor microenvironment is a complex niche that includes heterogeneous physical structures,unique biochemical gradients and multiple cell interactions.Its high-fidelity in vitro reconstruction is of fundamental importance to improve current understandings of cell behavior,efficacy predictions and drug safety.In this study,we have developed a high-throughput biochip with hundreds of composite extracellular matrix(ECM)microchambers to co-culture invasive breast cancer cells(MDA-MB-231-RFP)and normal breast epithelial cells(MCF-10 A-GFP).The composite ECM is composed of type I collagen and Matrigel which provides a heterogeneous microenvironment that is similar to that of in vivo cell growth.Additionally,the growth factors and drug gradients that involve human epidermal growth factor(EGF),discoidin domain receptor 1(DDR1)inhibitor 7 rh and matrix metalloproteinase inhibitor batimastat allow for the mimicking of the complex in vivo biochemical microenvironment to investigate their effect on the spatial-temporal dynamics of cell growth.Our results demonstrate that the MDA-MB-231-RFP cells and MCF-10 A-GFP cells exhibit different spatial proliferation behaviors under the combination of growth factors and drugs.Basing on the experimental data,we have also developed a cellular automata(CA)model that incorporated drug diffusion to describe the experimental phenomenon,as well as employed Shannon entropy(SE)to explore the effect of the drug diffusion coefficient on the spatial-temporal dynamics of cell growth.The results indicate that the uniform cell growth is related to the drug diffusion coefficient,which reveals that the pore size of the ECM plays a key role in the formation of complex biochemical gradients.Therefore,our integrated,biomimetic and high-throughput co-culture platforms,as well as the computational model can be used as an effective tool for investigating cancer pathogenesis and drug development.
文摘Computational models of eye-movement control during reading provide precise quantitative descriptions of the perceptual, cognitive, and motoric processing that guide readers′ eyes, but are based on numerous equivocal a priori theoretical assumptions. This article describes an alternative approach to understanding eye-movement control: Using reinforcement learning to examine how complex eye-movement behaviors emerge from the requirement to identify words rapidly in the context of known psychological and physiological constraints(e.g., limited visual acuity). An example simulation is reported, as are key results from an fMRI experiment that demonstrates that structures implicated in reinforcement learning support the learning of eye-movement behavior in humans.
文摘The purpose of rural informationization is to provide effective information for farmers,increase production efficiency and income level of farmers in agricultural production.In recent years,under the guidance of No.1 document of central government,China's rural informationization has obtained considerable development.However,due to influence of terrain,mountain areas are still backward in informationization development.Combining actual conditions of Pingshan County of Hebei Province,the authors visited local farmers and made detailed survey on basic conditions of farmers,and analyzed factors obstructing agricultural informationization development in mountain areas,to provide theoretical reference for promoting informationization development in mountain areas and increasing income of local farmers.
文摘Community facilities accidents happen every year in many cities of China, which has been an important issue in academic circles. The purpose of this study is to suggest the direction of universal design for the prevention of community facilities accidents. In this paper, from the overall angle, the impact factors of the urban community service facilities safety were analyzed. Then, based on the integrated governance theory, from such aspects as engineering and non-engineering disaster reduction, the governance measures were explored.
文摘Objective:To investigate the potential value of PDT(photodynamic therapy)in the treatment of rectal cancer by reviewing the diagnosis and treatment process of a patient with advanced rectal cancer who lost the opportunity of surgery.Methods:Select the case data of a patient receiving photodynamic therapy in our hospital,and analyze the photodynamic mechanism safety and efficiency,and discuss the efficacy of photodynamic therapy.Results:After the patient received photodynamic therapy,re-examination of the endoscopy showed that the intestinal cavity was smoother than before,the bowel was difficult,and the symptoms of blood in the stool improved.Conclusion:Photodynamic therapy can be used as a radical or palliative treatment for clinical tumor treatment.Because of its advantages of minimally invasive,tissue-specific,repetitive and synergistic radiotherapy and chemotherapy,it plays an important role in early or middle-advanced colorectal cancer and is worthy of clinical promotion.
基金supported by the National Natural Science Foundation of China(U1809214)the Natural Science Foundation of Zhejiang Province(LY20E080014,LTGN23E080001)the Science and Technology Project of Zhoushan(2022C41011)。
