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.

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.

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.

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.

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.

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.

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.

A Comparative Study on the Dominant Factors Responsible for the Weaker-than-expected El Ni?o Event in 2014

Anomalous warming occurred in the equatorial central-eastern Pacific in early May 2014, attracting much attention to the possible occurrence of an extreme E1 Nifio event that year because of its similarity to the situation in early 1997. However, the subsequent variation in sea surface temperature anomalies （SSTAs） during summer 2014 in the tropical Pacific was evidently different to that in 1997, but somewhat similar to the situation of the 1990 aborted E1 Nifio event. Based on NCEP （National Centers for Environmental Prediction） oceanic and atmospheric reanalysis data, the physical processes responsible for the strength of E1 Nifio events are examined by comparing the dominant factors in 2014 in terms of the preceding instability of the coupled ocean-atmosphere system and westerly wind bursts （WWBs） with those in 1997 and 1990, separately. Although the unstable ocean-atmosphere system formed over the tropical Pacific in the preceding winter of 2014, the strength of the preceding instability was relatively weak. Weak oceanic eastward-propagating downwelling Kelvin waves were forced by the weak WWBs over the equatorial western Pacific in March 2014, as in February 1990. The consequent positive upper-oceanic heat content anomalies in the spring of 2014 induced only weak positive SSTAs in the central-eastern Pacific-unfavorable for the subsequent generation of summertime WWB sequences. Moreover, the equatorial western Pacific was not cooled, indicating the absence of positive Bjerknes feedback in early summer 2014. Therefore, the development of E1 Nifio was suspended in summer 2014.

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.

Maintenance of an abrupt boundary between needle-leaved and broad-leaved forests in a wetland near coast

There is an abrupt boundary between two well-developed wetland forests, a stand consisting of a broad-leaved, nitrogen-fixer Alnusjaponica and a stand of the needle-leaved Picea glehnii Masters, in eastern Hokkaido, Japan. To clarify maintenance mechanisms, we studied the forest profile, water level, groundwater and precipitation chemistry, seedling establishment patterns in relation to microhabitats, and seed migration. The profile of groundwater level insufficiently explained the abrupt boundary formation, while the groundwater chemistry differed significantly between the two forests ; i.e., EC, Na^＋, K^＋, Mg^2＋, Ca^2＋ and Cl^- were higher in P. glehnii forest and pH was lower. Precipitation in P. glehnii forest contained richer Na＋, Ca^2＋ and Cl^-, indicating that the differences in surface-water chemistry were mostly derived from precipitation. Solar radiation was less than 2.2 MJ.m^-2.d^-1 on P. glehnii forest in late June, while that was patchily distributed in A.japonica forest with a range from 1.0 to 3.7 MJ＇m^-2＇d^-1. Moss cover on the soil surface, most of which were made of Sphagnum spp., was 60% in P. glehnii forest, but was 10% in A. japonica forest. Surface water chemistry represented by pH was considered to determine the development of Sphagnum moss. About 70% of P. glehnii seedlings 〈 1.3 m in height established on moss cover. Seed-sowing experiments suggested that seed germination and seedling survival for both species were significantly higher in P. glehnii forest. Therefore, the regeneration of P. glehnii in A. japonica forest was negligible, owing to the paucity of favorable microhabitats and low seedling establishment. A. japonica regenerated only by resprouting, and the seedlings were few in both forests. In addition, A. japonica seed migration into the P. glehnii forests was greatly restricted, and low solar radiation in the P. glehnii forest contributed to low seedling survival. Based on those results, we concluded that Picea glehnii and Alnusjaponica could develop distinct and selfish environments being unsuitable for the other species and inhibit natural afforestation of another species each other by excluding invasion.

Roles of Equatorial Ocean Currents in Sustaining the Indian Ocean Dipole Peak

In this study,on the basis of the results of the European Centre for Medium-Range Weather Forecasts Ocean Reanalysis System 4,the response of equatorial ocean currents and their roles during the peak phase of the Indian Ocean Dipole(IOD)are comprehensively explored.During the IOD peak season,a series of ocean responses emerge.First,significant meridional divergence in the surface layer and convergence in the subsurface layer are found in the equatorial region.The equatorial easterly winds and offequatorial wind curl anomalies are found to be responsible for the divergence at 55°–80°E and the convergence at 70°–90°E.Second,the meridional divergence and convergence are found to favor a weakened Wyrtki jet(WJ)in the surface layer and an enhanced Equatorial Undercurrent(EUC)in the subsurface layer,respectively.Therefore,these ocean responses provide ocean positive feedback that sustains the IOD peak as the weakened WJ and enhanced EUC help maintain the zonal temperature gradient.Additionally,heat budget analyses indicate that the weakened WJ favors sea surface temperature anomaly warming in the western Indian Ocean,whereas the enhanced EUC maintains the sea surface temperature anomaly cooling in the eastern Indian Ocean.