Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaini...Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaining an acceptable image size. We have followed here a different path to accelerate data acquisition by improving the feedback loop to achieve the same SPM image quality in a shorter time. While the feedback loop in a scanning probe microscope typically starts to probe a new pixel starting from the previous position, we have reduced the total control time by using an improved starting point for the feedback loop at each pixel. By exploiting the information of the already scanned pixels a forecast for the new pixel is created. We have successfully used several simple methods for a prognosis in MATLAB simulations like one dimensional linear or cubic extrapolation and others. Only scanning tunnelling microscope data from real experiments were used to test the forecasts. A doubling of the speed was achieved in the most favourable cases.展开更多
Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and...Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and S-function simulation block of asynchronous motor owing feedback function was built in Matlab/Simulink software, the simulation block indicates that motor rotation speed and its output moment vary with load and time, and the motor is a dynamic feedback system in working process. The state space block was adopted to express model of the belt. Thus it created simulation model of established dynamic model of overall belt conveyor system with Mat- lab/Simulink software, and simulates the course of starting by properly setting simulation parameters, and processes data for visualization.展开更多
<Abstract>The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplicative Gaussian coloured noise and additive Gaussian white noise is investi...<Abstract>The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplicative Gaussian coloured noise and additive Gaussian white noise is investigated.Firstly,the analytic expression of the quasi-steady distribution function Ps(x,t) is derived by applying the unified eoloured noise approximation and the Novikov Theorem;Secondly,the expression of the signal-to-noise ratio (SNR) is obtained in the adiabatic limit to quantify the stochastic resonance.Finally,the effects of the linear coefficient a,the nonlinear coefficient b,the linear time-delayed feedback coefficient c and the delay time τ on P_s(x,t) and SNR~± are discussed.It is found that the effects of the linear coefficient and the nonlinear coefficient,the positive linear time-delayed feedback coefficient and the negative linear time-delayed feedback coefficient,the positive delayed time and the negative delayed time on P_s(x,t) and SNR~± are different,respectively.This discussion would be helpful to the study of the system reliability and controlling stochastic resonance.展开更多
The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and PP2A...The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and PP2A.Targeting aberrant SET represents a promising strategy for cancer intervention.However,the mechanism by which endogenous SET is regulated in cancer cells remains largely unknown.Here,we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer cells.In addition,p53 stimulated PP2A phosphatase activity via p53-mediated transcriptional repression of SET,whereby SET-mediated inhibition of PP2A was alleviated.Moreover,targeting the interaction between SET and PP2A catalytic subunit(PP2Ac)with FTY720 enhanced stress-induced p53 activation via PP2A-mediated dephosphorylation of p53 on threonine 55(Thr55).Therefore,our findings uncovered a previously unknown p53-SETPP2A regulatory feedback loop.To functionally potentiate this feedback loop,we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor suppression.Our study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2A feedback loop.展开更多
Background Cancer-associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor-derived extracellular vesicles (EVs) are the critical...Background Cancer-associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor-derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor-derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor-derived EV-mediated CAFs phenotype in regulating BCa LN metastasis. Methods The high-throughput sequencing was utilized to identify the crucial long non-coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665-mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient-derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. Results We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF-associated long non-coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B-induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B-HGF-c-Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV-transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. Conclusion Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B-HGF-c-Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.展开更多
Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipa...Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients.Aloperine(ALO)is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation,allergies and infection.However,its therapeutic efficacy and underlying mechanism in CC are still unclear.In the current study,MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC.Then,the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry,respectively,while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay.Moreover,nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo.The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis.This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest.Simultaneously,ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio.Additionally,the migration and invasion of HeLa cells were attenuated by ALO treatment,which was considered to result from inhibition of epithelial-to-mesenchymal transition.For molecular mechanisms,the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment.This study indicated that ALO markedly suppresses the proliferation,migration and invasion and enhances the apoptosis of HeLa cells.In addition,these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.展开更多
Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the mole...Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.展开更多
Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes...Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.展开更多
Trichomes are universally present in plants and their development is delicately regulated.Trichomes are responsible for pubescence,whose density is associated with some agronomic traits such as insect resis-tance,evap...Trichomes are universally present in plants and their development is delicately regulated.Trichomes are responsible for pubescence,whose density is associated with some agronomic traits such as insect resis-tance,evapotranspiration,and yield.Almost a century ago,three dominant alleles related to pubescence density in soybean,namely Pd1(dense pubescence),Ps(sparse pubescence),and P1(glabrous),were iden-tified.However,their molecular identity and genetic relationships remain unclear.In this study,through a genome-wide association study and map-based cloning,we determined the genetic basis of these three traits.The sparse-pubescence phenotype of Ps was attributed to a copy-number variation of a 25.6-kb sequence that includes a gene encoding a protein with WD40 and RING domains.The dense-pubescence phenotype of Pd1 was attributed to a T-C transition in the last exon of an HD-Zip transcription factor gene,and the glabrous phenotype of P1 was caused by a G-A transition in the first exon of a lipid transfer protein gene.Genetic and biochemical analyses revealed that Pd1 functions as a transcriptional activator that can bind the promoters of the P1 and Ps genes to induce their expression;Interestingly,Pd1 can also bind its own promoter and inhibit its gene transcription.In addition,Ps can interact with Pd1 and weaken the tran-scriptional activity of Pd1.Taken together,our results demonstrate that Pd1,Ps,and P1 form a complex feedback loop to regulate pubescence formation in soybean.展开更多
We propose an all-optical WDM buffer for optical packet switching system, which consists of NOLM and feedback loop. The proposed structure provides more than 40 turn buffering and nice output of buffered data when sel...We propose an all-optical WDM buffer for optical packet switching system, which consists of NOLM and feedback loop. The proposed structure provides more than 40 turn buffering and nice output of buffered data when selected by control signal.展开更多
Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this...Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this basis, this paper proposes dual loop feedback pre-distortion, which uses two first-order Volterra filter models to reduce the computing complexity and a dynamic error adjustment model to construct a revised feedback to ensure a better pre-distortion performance. The computation complexity, iterative convergence speed and precision of the proposed method are theoretically analyzed. Simulation results show that this dual loop feedback pre-distortion can speed the updating of coefficients and ensure the linearity of the amplifier output.展开更多
As the competition from companies in low cost countries increases,the need for more automated production which reduces labour cost while improving product quality is required.A new rotary compression bending set-up wi...As the competition from companies in low cost countries increases,the need for more automated production which reduces labour cost while improving product quality is required.A new rotary compression bending set-up with automated closed-loop feedback control is thus being developed.By transferring in-process measurement data into an algorithm for predicting springback and bend angle prior to the unloading sequence,the dimensional accuracy is improved.This work focuses on the development of this steering model.Since the method used does not increase cycle time,it is attractive for high-volume industrial applications.More than 150 bending tests of AA6060 extrusions were conducted to determine the capability of the technology.The results show that by activating the automated closed-loop feedback system,the dimensional accuracy of the bent parts is more than three times better than that obtained by traditional compression bending.Since the steering model permits the direct use of additional process data,such as instant wall thickness and cross sectional distortions,it is believed that extension of the measurement capabilities would improve the accuracy of the methodology even further.展开更多
Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown co...Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown correlation didn't make reliability analysis accurately based on existing GO methodology. So, a reliability analysis method used to deal with DICLFL considering shutdown correlation is provided based on GO methodology.Firstly, a new operator, which is used to describe DICLFL considering shutdown correlation,whose number is 1,is created and named as Type 9C operator. And then,the formulas of type 9C operator are derived based on Markov process theory. Finally,the new method presented in this paper is adopted to conduct the reliability analysis of an electro-hydraulic servo speed control system. The analysis result is compared with those of Monte Carlo simulation and fault tree analysis( FTA). The comparison results show that this new reliability analysis method based on GO methodology is feasible and meaningful for reliability analysis of repairable systems with DICLFL considering shutdown correlation.Meantime,it will be useful for more other applications.展开更多
A general multiple-loop feedback approach for realization of Four-Terminal Floating Nullor RC(FTFN-RC) filter is presented.The proposed filter is constructed by multi-output FTFNs, capacitors and resistors.It can simu...A general multiple-loop feedback approach for realization of Four-Terminal Floating Nullor RC(FTFN-RC) filter is presented.The proposed filter is constructed by multi-output FTFNs, capacitors and resistors.It can simultaneously realize slow-pass, band-pass(if order is even number), and high-pass filter responses.With RC elements grounded and requiring no component matching con-straints, it is fully integrated conveniently.Simulations are performed for the fourth-order Butterworth filter to verify the validity of the circuit.展开更多
文摘Scanning probe microscopes (SPM) are limited in their speed of data acquisition by the mechanical stability of the scanner. Therefore many types of scanners have been developed to achieve a rigid setup while maintaining an acceptable image size. We have followed here a different path to accelerate data acquisition by improving the feedback loop to achieve the same SPM image quality in a shorter time. While the feedback loop in a scanning probe microscope typically starts to probe a new pixel starting from the previous position, we have reduced the total control time by using an improved starting point for the feedback loop at each pixel. By exploiting the information of the already scanned pixels a forecast for the new pixel is created. We have successfully used several simple methods for a prognosis in MATLAB simulations like one dimensional linear or cubic extrapolation and others. Only scanning tunnelling microscope data from real experiments were used to test the forecasts. A doubling of the speed was achieved in the most favourable cases.
文摘Synthesizing the mechanical models of the belt, the driver and the take-up device, the dynamics model was established on the longitudinal vibration of the overall belt conveyor system with finite elemental method, and S-function simulation block of asynchronous motor owing feedback function was built in Matlab/Simulink software, the simulation block indicates that motor rotation speed and its output moment vary with load and time, and the motor is a dynamic feedback system in working process. The state space block was adopted to express model of the belt. Thus it created simulation model of established dynamic model of overall belt conveyor system with Mat- lab/Simulink software, and simulates the course of starting by properly setting simulation parameters, and processes data for visualization.
基金supported by National Natural Science Foundation of China under Grant Nos.10472091 and 10332030
文摘<Abstract>The phenomenon of stochastic resonance of a bistable system subjected to linear time-delayed feedback loops driven by multiplicative Gaussian coloured noise and additive Gaussian white noise is investigated.Firstly,the analytic expression of the quasi-steady distribution function Ps(x,t) is derived by applying the unified eoloured noise approximation and the Novikov Theorem;Secondly,the expression of the signal-to-noise ratio (SNR) is obtained in the adiabatic limit to quantify the stochastic resonance.Finally,the effects of the linear coefficient a,the nonlinear coefficient b,the linear time-delayed feedback coefficient c and the delay time τ on P_s(x,t) and SNR~± are discussed.It is found that the effects of the linear coefficient and the nonlinear coefficient,the positive linear time-delayed feedback coefficient and the negative linear time-delayed feedback coefficient,the positive delayed time and the negative delayed time on P_s(x,t) and SNR~± are different,respectively.This discussion would be helpful to the study of the system reliability and controlling stochastic resonance.
基金supported by Beijing Municipal Natural Science Foundation(7192126)the National Natural Science Foundation of China(81872311,82073132,82122054,and 81720108027)+1 种基金the National Key R&D Program of China(2019YFC1005200,and 2019YFC1005201)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-016)。
文摘The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and PP2A.Targeting aberrant SET represents a promising strategy for cancer intervention.However,the mechanism by which endogenous SET is regulated in cancer cells remains largely unknown.Here,we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer cells.In addition,p53 stimulated PP2A phosphatase activity via p53-mediated transcriptional repression of SET,whereby SET-mediated inhibition of PP2A was alleviated.Moreover,targeting the interaction between SET and PP2A catalytic subunit(PP2Ac)with FTY720 enhanced stress-induced p53 activation via PP2A-mediated dephosphorylation of p53 on threonine 55(Thr55).Therefore,our findings uncovered a previously unknown p53-SETPP2A regulatory feedback loop.To functionally potentiate this feedback loop,we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor suppression.Our study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2A feedback loop.
基金funded by the National Key Research and Development Program of China(Grant No.2022YFA1305500 and 2018YFA0902803)the National Natural Science Foundation of China(Grant No.82173272,82173271,81825016,82103536,82103416,81871945 and 81902589)+1 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2021B1515020091,2020A1515010815,2018B010109006,and 2021A1515010355)the Science and Technology Program of Guangzhou,China(Grant No.202002030388,201803010049,and 2017B020227007).
文摘Background Cancer-associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor-derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor-derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor-derived EV-mediated CAFs phenotype in regulating BCa LN metastasis. Methods The high-throughput sequencing was utilized to identify the crucial long non-coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665-mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient-derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. Results We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF-associated long non-coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B-induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B-HGF-c-Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV-transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. Conclusion Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B-HGF-c-Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.
基金This work was supported by the National Natural Science Foundation of China(No.82001850)Shanxi Basic Application Research(No.201901D211491)+2 种基金the Scientific Research Project of Shanxi Health Commission(No.2019038)the Doctoral Research Project of Shanxi Medical University(No.XD1901)the Doctoral Research Project of Shanxi Province(No.SD1901).
文摘Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system worldwide.The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients.Aloperine(ALO)is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation,allergies and infection.However,its therapeutic efficacy and underlying mechanism in CC are still unclear.In the current study,MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC.Then,the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry,respectively,while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay.Moreover,nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo.The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis.This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest.Simultaneously,ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio.Additionally,the migration and invasion of HeLa cells were attenuated by ALO treatment,which was considered to result from inhibition of epithelial-to-mesenchymal transition.For molecular mechanisms,the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment.This study indicated that ALO markedly suppresses the proliferation,migration and invasion and enhances the apoptosis of HeLa cells.In addition,these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
基金National Natural Science Foundation of China,Grant/Award Number:81901006Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2020A1515110051+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University,Grant/Award Number:RC202005Science Research Cultivation Program of Stomatological Hospital,Southern Medical University,Grant/Award Number:PY2020002。
文摘Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.
基金Project of Jiangsu Provincial Medical Talent,Grant/Award Number:ZDRCA2016033China Postdoctoral Science Foundation,Grant/Award Number:2018M640465+2 种基金National Natural Science Foundation of China,Grant/Award Numbers:81672295,81702265,81802277,81872378Research Program of Jiangsu Health Department,Grant/Award Number:LGY2016025Social Development Project of Jiangsu Province,Grant/Award Number:BE2019758。
文摘Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.
基金the National Key Research and Development Program(2016YFD0100401)the Ministry of Agriculture of the People's Republic of China(2016ZX08009003)the National Natural Science Foundation of China(grant nos.32001501,31788103,and 31525018).
文摘Trichomes are universally present in plants and their development is delicately regulated.Trichomes are responsible for pubescence,whose density is associated with some agronomic traits such as insect resis-tance,evapotranspiration,and yield.Almost a century ago,three dominant alleles related to pubescence density in soybean,namely Pd1(dense pubescence),Ps(sparse pubescence),and P1(glabrous),were iden-tified.However,their molecular identity and genetic relationships remain unclear.In this study,through a genome-wide association study and map-based cloning,we determined the genetic basis of these three traits.The sparse-pubescence phenotype of Ps was attributed to a copy-number variation of a 25.6-kb sequence that includes a gene encoding a protein with WD40 and RING domains.The dense-pubescence phenotype of Pd1 was attributed to a T-C transition in the last exon of an HD-Zip transcription factor gene,and the glabrous phenotype of P1 was caused by a G-A transition in the first exon of a lipid transfer protein gene.Genetic and biochemical analyses revealed that Pd1 functions as a transcriptional activator that can bind the promoters of the P1 and Ps genes to induce their expression;Interestingly,Pd1 can also bind its own promoter and inhibit its gene transcription.In addition,Ps can interact with Pd1 and weaken the tran-scriptional activity of Pd1.Taken together,our results demonstrate that Pd1,Ps,and P1 form a complex feedback loop to regulate pubescence formation in soybean.
文摘We propose an all-optical WDM buffer for optical packet switching system, which consists of NOLM and feedback loop. The proposed structure provides more than 40 turn buffering and nice output of buffered data when selected by control signal.
文摘Since the satellite communication goes in the trend of high-frequency and fast speed, the coefficients updating and the precision of the traditional pre-distortion feedback methods need to be further improved. On this basis, this paper proposes dual loop feedback pre-distortion, which uses two first-order Volterra filter models to reduce the computing complexity and a dynamic error adjustment model to construct a revised feedback to ensure a better pre-distortion performance. The computation complexity, iterative convergence speed and precision of the proposed method are theoretically analyzed. Simulation results show that this dual loop feedback pre-distortion can speed the updating of coefficients and ensure the linearity of the amplifier output.
文摘As the competition from companies in low cost countries increases,the need for more automated production which reduces labour cost while improving product quality is required.A new rotary compression bending set-up with automated closed-loop feedback control is thus being developed.By transferring in-process measurement data into an algorithm for predicting springback and bend angle prior to the unloading sequence,the dimensional accuracy is improved.This work focuses on the development of this steering model.Since the method used does not increase cycle time,it is attractive for high-volume industrial applications.More than 150 bending tests of AA6060 extrusions were conducted to determine the capability of the technology.The results show that by activating the automated closed-loop feedback system,the dimensional accuracy of the bent parts is more than three times better than that obtained by traditional compression bending.Since the steering model permits the direct use of additional process data,such as instant wall thickness and cross sectional distortions,it is believed that extension of the measurement capabilities would improve the accuracy of the methodology even further.
基金Technical Basis Projects of China's MIIT(Nos.ZQ092012B003,2012090003)
文摘Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown correlation didn't make reliability analysis accurately based on existing GO methodology. So, a reliability analysis method used to deal with DICLFL considering shutdown correlation is provided based on GO methodology.Firstly, a new operator, which is used to describe DICLFL considering shutdown correlation,whose number is 1,is created and named as Type 9C operator. And then,the formulas of type 9C operator are derived based on Markov process theory. Finally,the new method presented in this paper is adopted to conduct the reliability analysis of an electro-hydraulic servo speed control system. The analysis result is compared with those of Monte Carlo simulation and fault tree analysis( FTA). The comparison results show that this new reliability analysis method based on GO methodology is feasible and meaningful for reliability analysis of repairable systems with DICLFL considering shutdown correlation.Meantime,it will be useful for more other applications.
基金National Natural Science Foundation of China under Grant Nos.10747005 and 10602020Natural Science Foundation of the Education Department of Jiangsu Province of China under Grant No.08KJD110018
基金Supported by the Hunan Province Project of Education Department of Financial Aid (No.04C346)
文摘A general multiple-loop feedback approach for realization of Four-Terminal Floating Nullor RC(FTFN-RC) filter is presented.The proposed filter is constructed by multi-output FTFNs, capacitors and resistors.It can simultaneously realize slow-pass, band-pass(if order is even number), and high-pass filter responses.With RC elements grounded and requiring no component matching con-straints, it is fully integrated conveniently.Simulations are performed for the fourth-order Butterworth filter to verify the validity of the circuit.