Open AccessAmplifying colorectal cancer progression:impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p

Objective:Colorectal cancer(CRC)is a prevalent malignant tumor with a high fatality rate.CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator.Nevertheless,the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.Methods:Western blot,immunohistochemistry,and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression.The CCK-8 assay was used to assess cell growth.The Transwell assay was used to detect invasion and migration of cells.The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4(or SP1)bind to one another.An in vivo assay was used to measure tumor growth.Results:It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues.CircPDIA4 knockdown prevented the invasion,migration,and proliferation of cells in CRC.Additionally,the combination of circPDIA4 and miR-9-5p was confirmed,as well as miR-9-5p binding to SP1.Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC.In addition,SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription.CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.Conclusions:The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression.This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.

Controlling Chaos in a Semiconductor Laser via Weak Optical Positive Feedback and Modulating Amplitude

Numerical analysis of weak optical positive feedback （OPF） controlling chaos is studied in a semiconductor laser. The physical model of controlling chaos produced via modulating the current of semiconductor laser is presented under the condition of OPF. We find the physical mechanism that the nonlinear gain coefficient and linewidth enhance- ment factor of the laser are affected by OPF so that the dynamical behaviour of the system can be efficiently controlled. Chaos is controlled into a single-periodic state, a dual-periodic state, a tri-periodic state, a quadr-periodic state, a pentaperiodic state, and the laser emitting powers are increased by OPF in simulations. Lastly, another chaos-control method with modulating the amplitude of the feedback light is presented and numerically simulated to control chaotic laser into multi-periodic states.

Explosive synchronization in a mobile network in the presence of a positive feedback mechanism

Synchronization is a process that describes the coherent dynamics of a large ensemble of interacting units.The study of explosive synchronization transition attracts considerable attention.Here,I report the explosive transition within the framework of a mobile network,while each oscillator is controlled by global-order parameters of the system.Using numerical simulation,I find that the explosive synchronization(ES)transition behavior can be controlled by simply adjusting the fraction of controlled oscillators.The influences of some parameters on explosive synchronization are studied.Moreover,due to the presence of the positive feedback mechanism,I prevent the occurrence of the synchronization of continuous-phase transition and make phase transition of the system a first-order phase transition accompanied by a hysteresis loop.

Experimental study of delayed positive feedback control for a flexible beam

Recently, some researches indicate that positive feedback can benefit the control if appropriate time delay is intentionally introduced into control system. However, most work is theoretical one but few are experimental. This paper presents theoretical and experimental studies of delayed positive feedback control technique using a flexible beam as research object. The positive feedback weighting coefficient is designed by using the optimal control method. The available time delay is determined by analyzing the maximal real part of characteristic roots of the system. A DSP-based experiment system is introduced. Simulation and experimental results indicate that the delayed positive feedback control may effectively reduce the beam vibration if time delay is appropriately selected.

Hopf Bifurcation of a Positive Feedback Delay Differential Equation

Under some minor technical hypotheses, for each T larger than a certain rS > 0, Krisztin, Walther and Wu showed the existence of a periodic orbit for the positive feedback delay differential equation x(t) = -rμx(t) + rf(x(t-1)), where r and μ are positive constants and f : R → R satisfies f(0) = 0 and f' > 0. Combining this with a unique result of Krisztin and Walther, we know that this periodic orbit is the one branched out from 0 through Hopf bifurcation. Using the normal form theory for delay differential equations, we show the same result under the condition that f ∈ C3(R,R) is such that f''(0) = 0 and f'''(0) < 0, which is weaker than those of Krisztin and Walther.

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma

Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

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.

Improvement of a highly sensitive and specific whole-cell biosensor by adding a positive feedback amplifier

In this study,we designed a Cd^(2+)whole-cell biosensor with both positive and negative feedback cascade am-plifiers in Pseudomonas putida KT2440(LTCM)based on our previous design with only a negative feedback amplifier(TCM).The results showed that the newly developed biosensor LTCM was greatly improved compared to TCM.Firstly,the linear response range of LTCM was expanded while the maximum linear response range was raised from 0.05 to 0.1μM.Meanwhile,adding a positive feedback amplifier further increased the fluorescence output signal of LTCM 1.11–2.64 times under the same culture conditions.Moreover,the response time of LTCM for detection of practical samples was reduced from 6 to 4 h.At the same time,LTCM still retained very high sensitivity and specificity,while its lowest detection limit was 0.1 nM Cd^(2+)and the specificity was 23.29(compared to 0.1 nM and 17.55 in TCM,respectively).In summary,the positive and negative feedback cascade amplifiers effectively improved the performance of the biosensor LTCM,resulting in a greater linear response range,higher output signal intensity,and shorter response time than TCM while retaining comparable sensitivity and specificity,indicating better potential for practical applications.

An Underwater Robot Inspection Anomaly Localization Feedback System Based on Sonar Technology

This article introduces an underwater robot inspection anomaly localization feedback system comprising a real-time water surface tracking,detection,and positioning system located on the water surface,while the underwater robot inspection anomaly feedback system is housed within the underwater robot.The system facilitates the issuance of corresponding mechanical responses based on the water surface’s real-time tracking,detection,and positioning,enabling recognition and feedback of anomaly information.Through sonar technology,the underwater robot inspection anomaly feedback system monitors the underwater robot in real-time,triggering responsive actions upon encountering anomalies.The real-time tracking,detection,and positioning system from the water surface identifies abnormal conditions of underwater robots based on changes in sonar images,subsequently notifying personnel for necessary intervention.

Substrate concentration effect on gene expression in genetic circuits with additional positive feedback

In gene regulatory networks, gene regulation loops often occur with multiple positive feedback, multiple negative feedback and coupled positive and negative feedback forms. In above gene regulation loops, auto-activation loops are ubiquitous regulatory motifs. This paper aims to investigate a two-component dual-positive feedback genetic circuit, which consists of a double negative feedback circuit and an additional positive feedback loop(APFL). We study effect of substrate concentration on gene expression in the single and the networked systems with APFLs, respectively. We find that substrate concentration can tune stochastic switch behavior in the signal system and then we explore relationship of substrate concentration with positive feedback strength in aspect of stochastic switch behavior. Furthermore, we also discuss gene expression and stochastic switch behavior in the networked systems with APFLs. Based on analysis in the networked systems, we discover that genes express in some specific cells and do not express in the other cells when the expression achieves its steady state. These results can be used to well explain the character of regionalization in the expression of genes and the phenomenon of gene differentiation.

PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop

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.

Meiotic nuclear divisions 1(MND1)fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma

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.

Asymmetries of Positive Feedback Trading in Individual Stocks:Evidences from China

The paper investigates the positive feedback trading phenomenon of individual stocks in China’s stock market.Heterogeneous regression models and a non-parametric Sentana-Wadhwani model are developed and applied to prove the existence of rise-favor asymmetric feedback trading.This result is consistent with the reality of China’s stock market,that is,the herding behavior of irrational retail investors has a significant influence on the market.However,the result is in contrast with the stylized findings using market indices.Further empirical research shows that this distinction could be explained by the average effect of indices.The asymmetries of positive feedback trading caused by heterogeneous feedback trading and the uneven distributed retail trading in individual stocks,are covered by the weighted average effect in indices.Therefore,the indices exhibit a different asymmetric pattern from that of individual stocks.

Black Phosphorus Nanosheets Enhance Photophosphorylation by Positive Feedback

We construct a natural-artificial hybrid architecture containing black phosphorus nanosheets(BPNS)to enhance photosynthesis of chloroplast in a positive-feedback manner.In this architecture,oxygen yielded by photosynthesis during water splitting by photosystemⅡpromotes the photoreaction of BPNS to produce proton and inorganic phosphate(Pi).Further,transmembrane proton gradient is increased to drive ATP synthase to synthesize ATP.Meanwhile,additional photogenerated electrons produced by BPNS are transferred to the photosynthesis process.As a consequence,photosynthesis performed by chloroplast is improved.Quantitatively,photophosphorylation efficacy of the hybrid system is increased by 1.89 times in the case of Pi deficiency.This work offers a new path to enhance solar-to-chemical energy conversion,holding promise in boosting natural photosynthesis.

Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell reprogramming

Retinoic acid(RA)and 2-phospho-L-ascorbic acid trisodium salt(AscPNa)promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.In the current studies,the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially.The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming.In addition,RA upregulated Glut1/3,facilitated the membrane transportation of dehydroascorbic acid,the oxidized form of L-ascorbic acid,and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time.On the other hand,AscPNa facilitated the mesenchymal-epithelial transition during reprogramming,downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1,subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA,and sustained the intracellular level of RA.Furthermore,the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition,pluripotency,and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination.Therefore,the current studies identified a positive feedback between RA and AscPNa,or possibility between vitamin A and C,and further explored their contributions to reprogramming.

Power Quality Assessment of Voltage Positive Feedback Based Islanding Detection Algorithm

Islanding refers to a condition where distributed generators(DGs)inject power solely to the local load after electrical separation from power grid.Several islanding detection methods(IDMs)categorized into remote,active,and passive groups have been reported to detect this undesirable state.In active techniques,a disturbance is injected into the DG’s controller to drift a local yardstick out of the permissible range.Although this disturbance leads to more effective detections even in well-balanced island,it raises the total harmonic distortion(THD)of the output current under the normal operation conditions.This paper analyzes the power quality aspect of the modified sliding mode controller as a new active IDM for grid-connected photovoltaic system(GCPVS)with a string inverter.Its performance is compared with the voltage positive feedback(VPF)method,a well-known active IDM.This evaluation is carried out for a 1 k Wp GCPVS in MATLAB/Simulink platform by measuring the output current harmonics and THD as well as the efficiency under various penetration and disturbance levels.The output results demonstrate that since the proposed disturbance changes the amplitude of the output current,it does not generate harmonics/subharmonics.Thereby,it has a negligible adverse effect on power quality.It is finally concluded that the performance of the sliding mode-based IDM is reliable from the standpoints of islanding detection and power quality.

Flow Control for a Two-Stage Proportional Valve with Hydraulic Position Feedback

The current research mainly focuses on the flow control for the two-stage proportional valve with hydraulic position feedback which is named as Valvistor valve.Essentially,the Valvistor valve is a proportional throttle valve and the flow fluctuates with the change of load pressure.The flow fluctuation severely restricts the application of the Valvistor valve.In this paper,a novel flow control method the Valvistor valve is provided to suppress the flow fluctuation and develop a high performance proportional flow valve.The mathematical model of this valve is established and linearized.Fuzzy proportional-integral-derivative(PID)controller is adopted in the closed-loop flow control system.The feedback is obtained by the flow inference with back-propagation neural network(BPNN)based on the spool displacement in the pilot stage and the pressure differential across the main orifice.The results show that inference with BPNN can obtain the flow data fast and accurately.With the flow control method,the flow can keep at the set point when the pressure differential across the main orifice changes.The flow control method is effective and the Valvistor valve changes from proportional throttle valve to proportional flow valve.For the developed proportional flow valve,the settling time of the flow is very short when the load pressure changes abruptly.The performances of hysteresis,linearity and bandwidth are in a high range.The linear mathematical model can be verified and the assumptions in the system modeling is reasonable.

Feedback Control of Plasma Current and Horizontal Position in HT-7

There is a strong magnetic coupling between poloidal field coils of superconducting tokamak HT-7, especially between ohinic heating and vertical field coils. These coils are connected to individual power supply. The control system for the plasma current and horizontal position control has been designed and showed satisfactory results with the feedback control of multivari- able feedforward-decoupling and var-parameter PID controller to simultaneously modulate power supplies. The design and analysls of the control system is presented.

Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs

Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species(ROS)levels at focal sites and the evolvement of antioxidant defense systems.Herein,we develop an albumin-based nanomedicine to co-deliver chlorin e6(Ce6)and COH-SR4(CS),which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy(PDT).In which,CS acts as both an activator of AMP-activated protein kinase(AMPK)and an inhibitor of glutathione S-transferases(GSTs).Benefiting from it,the prepared HSA-Ce6@COH-SR4(HCCS)enables positive feed-back uptake by promoting AMPK phosphorylation,leading to rapid and extensive tumor accumulation of drugs.As a result,HCCS obviously increases the ROS production to elevate intracellular oxidative stress.Furthermore,HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells,intensifying the oxidative damage of ROS.Ultimately,the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality,which greatly declines the proliferation of breast cancer in vivo.This study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.

A Study of Structure and Mechanism of a Meso-beta-scale Convective Vortex and Associated Heavy Rainfall in the Dabie Mountain Area Part I: Diagnostic Analysis of the Structure

An analysis was conducted on the evolutional process of a mesoscale convective vortex （MCV） and associated heavy rainfall in the Dabie Mountain area on 21-22 June 2008,as well as their structural characteristics in different stages,by using the mesoscale reanalysis data with 3 km and 1 h resolution generated by the Local Analysis and Prediction System （LAPS） in the Southern China Heavy Rainfall Experiment.The results showed that the latent heat released by convection in the midtroposphere was the main energy source for the development of a low-level vortex.There was a positive feedback interaction between the convection and the vortex,and the evolution of the MCV was closely related to the strength of the positive interaction.The most typical characteristics of the thermal structure in different stages were that,there was a relatively thin diabatic heating layer in the midtroposphere in the formative stage;the thickness of diabatic heating layer significantly increased in the mature stage;and it almost disappeared in the decay stage.The characteristics of the dynamic structure were that,in the formative stage,there was no anticyclonic circulation at the high level;in the mature stage,an anticyclonic circulation with strong divergence was formed at the high level;in the decay stage,the anticyclonic circulation was damaged and the high-level atmosphere was in a disordered state of turbulence.Finally,the structural schematics of the MCV in the formative and mature stage were established respectively.