Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality worldwide.Mesenchymal-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment.MET amplification has been reported in CRC,but data are very limited.Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice.AIM To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy.METHODS A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited.All patients were without RAS/RAF mutation or microsatellite instability-high.MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),respectively.Correlations between MET aberration and pathological features were detected using the chi-squared test.Progression free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank test.The results of MET FISH and IHC were com pared using one-way ANOVA.RESULTS Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not detected.Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(P<0.001)and higher tumor budding grade(P=0.02).In the survival analysis,significant difference was detected between patients with amplified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was detected between patients with different protein levels.In terms of concordance between MET FISH and IHC results,MET copy number showed no difference in c-MET IHC 0/1+(3.35±0.18),2+(3.29±0.11)and 3+(3.58±0.22)cohorts,and the MET-to-CEP7 ratio showed no difference in three groups(1.09±0.02,1.10±0.01,and 1.09±0.03).CONCLUSION In CRC,focal MET amplification was a rare event.Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis.IHC was a poor screening tool for MET amplification.

Research and Application of"Soft"Devices for Realizing Servo Amplification

This article analyzes and discusses the working principle and problems encountered by various servo amplification devices used in the on-site continuous adjustment system,analyzes and discusses the application of the servo mechanism,and analyzes the mechanism of the servo device's implementation of the"positioning"func-tion on the control device.Intended to guide the continuous adjustment process in controlling the function/accuracy of actuator equipment and application debugging,ensuring the safe and stable operation of production equipment and facilities.

Current trends in nanomaterials-mediated biosensing platforms and signal amplification strategies for antibiotics detection in dairy products

Dairy products have become one of the most prevalent daily foods worldwide,but safety concerns are rising.In dairy farming,unscrupulous traders misuse antibiotics to treat some diseases such as mastitis in cows,leading to antibiotic residues in dairy products.Rapid,sensitive,and simple detection methods for antibiotic residues are particularly important for food safety in dairy products.Traditional detection technology can effectively detect antibiotics,but there are defects such as complicated pre-treatment and high cost.Biosensors are widely used in food safety due to fast detection speed,low detection cost,strong anti-interference ability,and suitability for the field application.Nevertheless,these sensors often fail to trigger the signal conversion output due to low target concentration.To cope with this issue,some high-efficiency signal amplification systems can be introduced to improve the detection sensitivity and linear range of biosensors.In this review,we focused on:(i)Sources and toxicity of major antibiotics in animal-derived foods.(ii)Nanomaterial-mediated biosensors for real-time detection of target antibiotics in animal-derived foods.(iii)Signal amplification techniques to increase the sensitivity of biosensors.Finally,future prospects and challenges in this research field are discussed.

Assessment of future Antarctic amplification of surface temperature change under different Scenarios from CMIP6

Global warming may result in increased polar amplification,but future temperature changes under different climate change scenarios have not been systematically investigated over Antarctica.An index of Antarctic amplification(AnA)is defined,and the annual and seasonal variations of Antarctic mean temperature are examined from projections of the Coupled Model Intercomparison Project Phase 6(CMIP6)under scenarios SSP119,SSP126,SSP245,SSP370 and SSP585.AnA occurs under all scenarios,and is strongest in the austral summer and autumn,with an AnA index greater than 1.40.Although the warming over Antarctica accelerates with increased anthropogenic forcing,the magnitude of AnA is greatest in SSP126 instead of in SSP585,which may be affected by strong ocean heat uptake in high forcing scenario.Moreover,future AnA shows seasonal difference and regional difference.AnA is most conspicuous in the East Antarctic sector,with the amplification occurring under all scenarios and in all seasons,especially in austral summer when the AnA index is greater than 1.50,and the weakest signal appears in austral winter.Differently,the AnA over West Antarctica is strongest in austral autumn.Under SSP585,the temperature increase over the Antarctic Peninsula exceeds 0.5℃when the global average warming increases from 1.5℃to 2.0℃above preindustrial levels,except in the austral summer,and the AnA index in this region is strong in the austral autumn and winter.The projections suggest that the warming rate under different scenarios might make a large difference to the future AnA.

Influence of Surface Types on the Seasonality and Inter-Model Spread of Arctic Amplification in CMIP6

A robust phenomenon termed the Arctic Amplification(AA)refers to the stronger warming taking place over the Arctic compared to the global mean.The AA can be confirmed through observations and reproduced in climate model simulations and shows significant seasonality and inter-model spread.This study focuses on the influence of surface type on the seasonality of AA and its inter-model spread by dividing the Arctic region into four surface types:ice-covered,ice-retreat,ice-free,and land.The magnitude and inter-model spread of Arctic surface warming are calculated from the difference between the abrupt-4×CO_(2)and pre-industrial experiments of 17 CMIP6 models.The change of effective thermal inertia(ETI)in response to the quadrupling of CO_(2) forcing is the leading mechanism for the seasonal energy transfer mechanism,which acts to store heat temporarily in summer and then release it in winter.The ETI change is strongest over the ice-retreat region,which is also responsible for the strongest AA among the four surface types.The lack of ETI change explains the nearly uniform warming pattern across seasons over the ice-free(ocean)region.Compared to other regions,the ice-covered region shows the maximum inter-model spread in JFM,resulting from a stronger inter-model spread in the oceanic heat storage term.However,the weaker upward surface turbulent sensible and latent heat fluxes tend to suppress the inter-model spread.The relatively small inter-model spread during summer is caused by the cancellation of the inter-model spread in ice-albedo feedback with that in the oceanic heat storage term.

Nonlinear optical imaging by detection with optical parametric amplification(invited paper)

Nonlinear optical imaging is a versatile tool that has been proven to be exceptionally useful in various research fields.However,due to the use of photomultiplier tubes(PMTs),the wide application of nonlinear optical imaging is limited by the incapability of imaging under am-bient light.In this paper,we propose and demonstrate a new optical imaging detection method based on optical parametric amplification(OPA).As a nonlinear optical process,OPA in-trinsically rejects ambient light photons by coherence gating.Periodical poled lithium niobate(PPLN)crystals are used in this study as the media for OPA.Compared to bulk nonlinear optical crystals,PPLN crystals support the generation of OPA signal with lower pump power.Therefore,this characteristic of PPLN crystals is particularly beneficial when using high-repetition-rate lasers,which facilitate high-speed optical signal detection,such as in spec-troscopy and imaging.A PPLN-based OPA system was built to amplify the emitted imaging signal from second harmonic generation(SHG)and coherent anti-Stokes Raman scattering(CARS)microscopy imaging,and the amplified optical signal was strong enough to be detected by a biased photodiode under ordinary room light conditions.With OPA detection,ambient-light-on SHG and CARS imaging becomes possible,and achieves a similar result as PMT detection under strictly dark environments.These results demonstrate that OPA can be used as a substitute for PMTs in nonlinear optical imaging to adapt it to various applications with complex.light ing conditions.

Ultrathin metal-organic framework nanosheets (Cu-TCPP)-based isothermal nucleic acid amplification for food allergen detection

The rapid and accurate detection of peanuts and soybeans allergen is important to the food safety. In this study, Cu-TCPP nanosheet, a kind of ultra-thin metal-organic framework(MOF)was synthesized and applied in loop-mediated isothermal amplification(named Cu-TCPP@LAMP), which can inhibit the non-specific amplification by absorbing and precise temperature releasing of single primer. As thus, Cu-TCPP@LAMP can achieve high sensitivity and specific amplification of the target gene. As a result, peanut and soybean allergens genes contained in food were successfully detected with a favorable detection sensitivity(5 ng/μL for peanuts and 10 ng/μL for soybeans)and reliable repeatability(The coefficient of variation was 3.38% for peanuts and 3.33% for soybeans). Moreover, the established method was utilized for detection of several commercial products, and had a high consistency with the standard method. Apart from food allergens, this novel assay can be widely used in other areas, such as pathogen detection, tumor nucleic acid detection and so on.

Spatio-temporal variations of Arctic amplification and their linkage with the Arctic oscillation

The Arctic near-surface air temperatures are increasing more than twice as fast as the global average-a feature known as Arctic amplification （AA）. A modified AA index is constructed in this paper to emphasize the contrast of warming rate between polar and mid-latitude regions, as well as the spatial and temporal characteristics of AA and their influence on atmospheric circulation over the Northern Hemisphere. Results show that AA has a pronounced annual cycle. The positive or negative phase activities are the strongest in autumn and winter, the weakest in summer. After experiencing a remarkable decadal shift from negative to positive phase in the early global warming hiatus period, the AA has entered into a state of being enlarged continuously, and the decadal regime shift of AA in about 2002 is affected mainly by decadal shift in autumn. In terms of spatial distribution, AA has maximum warming near the surface in almost all seasons except in summer. Poleward of 20~N, AA in autumn has a significant influence on the atmospheric circulation in the following winter. The reason may be that the autumn AA increases the amplitude of planetary waves, slows the wave speeds and weakens upper-level zonal winds through the thermal wind relation, thus influencing surface air temperature in the following winter. The AA correlates to negative phase of the Arctic oscillation （AO） and leads AO by 0-3 months within the period 1979-2002. However, weaker relationship between them is indistinctive after the decadal shift of AA.

Research progress and prospects of nucleic acid isothermal amplification technology

Nucleic acid(DNA and RNA)detection and quantification methods play vital roles in molecular biology.With the development of molecular biology,isothermal amplification of DNA/RNA,as a new molecular biology technology,can be amplified under isothermal condition,it has the advantages of high sensitivity,high specificity,and high efficiency,and has been applied in various fields of biotechnology,including disease diagnosis,pathogen detection,food hygiene and safety detection and so on.This paper introduces the progress of isothermal amplification technology,including rolling circle amplification(RCA),nucleic acid sequence-dependent amplification(NASBA),strand displacement amplification(SDA),loop-mediated isothermal amplification(LAMP),helicase-dependent amplification(HDA),recombinase polymerase amplification(RPA),cross-priming amplification(CPA),and its principle,advantages and disadvantages,and application development are briefly summarized.

Enhanced phase sensitive amplification towards improving noise immunity

Quantum states are essential resource for quantum-enhanced applications.Loss incurred in the distribution channel,however,dissipates the high signal-to-noise ratio advantage enjoyed by the squeezed state.Here,we first demonstrate noise immunity enhancement by using phase-sensitive amplifier(PSA)with measurement-based noiseless linear amplifier(MB-NLA).We explore the signal transfer capability with the amplifier in a noisy channel.The MB-NLA enhanced PSA has obvious suppression effect on channel noises,especially it has improvement for the noise contaminated signal.Better performance can be achieved by flexibly adjusting amplifier parameters.With the amplifier,it is promising to overcome the entanglement-distribution loss and show its superiority in squeezing based quantum sensing.

Influence of coupling asymmetry on signal amplification in a three-node motif

The three-node feedforward motif has been revealed to function as a weak signal amplifier. In this motif, two nodes(input nodes) receive a weak input signal and send it unidirectionally to the third node(output node). Here, we change the motif's unidirectional couplings(feedforward) to bidirectional couplings(feedforward and feedback working together).We find that a small asymmetric coupling, in which the feedforward effect is stronger than the feedback effect, may enable the three-node motif to go through two distinct dynamic transitions, giving rise to a double resonant signal response. We present an analytical description of the double resonance, which agrees with the numerical findings.

Development and Characterization of Microsatellite Markers for Harpadon nehereus Based on High-Throughput Sequencing and Cross-Species Amplification in Three Myctophiformes Fishes

Harpadon nehereus is a widespread economical fish found in the coastal seas of China and has important ecological value in the marine ecosystem.H_(o)wever,its germplasm resources have been seriously degraded due to natural factors and anthropogenic activities.In this study,high-throughput sequencing was applied to search for microsatellite loci in H.nehereus transcriptome to provide references for its resource conservation and utilization.Polymorphic loci were developed by non-denaturing polyacrylamide gel electrophoresis,and their cross-species amplified ability was detected in three related species.A total of 5652 microsatellites were identified from 16974320 unigenes.Among the primer pairs designed for 100 SSRs for PCR amplification,80%were successfully amplified,and 26 loci were polymorphic with a high number of alleles from 3 to 11 each.The expected(H_(e))and observed(H_(o))heterozygosities were 0.355–0.885 and 0.375–0.958,respectively.Most of the loci were highly polymorphic(polymorphism information content:0.316–0.852;mean:0.713),and these markers can be applied in the population genetic diversity research of H.nehereus.H_(o)wever,the transferability of these primers was low,probably because of the close relation of the collected species.In follow-up work,simple sequence repeats will be excavated with genome-based technologies,and related species will be gathered to address the present inadequacies.

Dissipation and amplification management in an electrical model of microtubules: Hybrid behavior network

The control of dissipation and amplification of solitary waves in an electrical model of a microtubule is demonstrated.This model consists of a shunt nonlinear resistance–capacitance(J(V)–C(V)) circuit and a series resistance–inductance(R–L) circuit. Through linear dispersion analysis, two features of the network are found, that is, low bandpass and bandpass filter characteristics. The effects of the conductance’s parameter λ on the linear dispersion curve are also analyzed. It appears that an increase of λ induces a decrease(an increase) of the width of the bandpass filter for positive(negative) values of λ. By applying the reductive perturbation method, we derive the equation governing the dynamics of the modulated waves in the system. This equation is the well-known nonlinear Schr?dinger equation extended by a linear term proportional to a hybrid parameter σ, i.e., a dissipation or amplification coefficient. Based on this parameter, we successfully demonstrate the hybrid behavior(dissipation and amplification) of the system. The exact and approximate solitary wave solutions of the obtained equation are derived, and the effects of the coefficient σ on the characteristic parameters of these waves are investigated. Using the analytical solutions found, we show numerically that the waves that are propagated throughout the system can be dissipated, amplified, or remain stable depending on the network parameters. These results are not only in agreement with the analytical predictions, but also with the existing experimental results in the literature.

Straightforward Method for Nonlinear Oscillators

It is challenging to predict the frequency property of a nonlinear vibration system conveniently and efficiently.Especially,an invalid or physically irrelevant result might be obtained by some advanced methods.Therefore,predicting the frequency lacks an expedient and efficient method.This challenge is addressed by developing a straightforward and effective frequency formulation that reliably predicts the frequency-amplitude relationship.This study provides a one-step approach which can fast determine the periodic properties of any conservative oscillators and also provides a reference for other similar studies.

Personal glucose meters coupled with signal amplification technologies for quantitative detection of non-glucose targets:Recent progress and challenges in food safety hazards analysis

Ensuring food safety is paramount worldwide.Developing effective detection methods to ensure food safety can be challenging owing to trace hazards,long detection time,and resource-poor sites,in addition to the matrix effects of food.Personal glucose meter(PGM),a classic point-of-care testing device,possesses unique application advantages,demonstrating promise in food safety.Currently,many studies have used PGM-based biosensors and signal amplification technologies to achieve sensitive and specific detection of food hazards.Signal amplification technologies have the potential to greatly improve the analytical performance and integration of PGMs with biosensors,which is crucial for solving the challenges associated with the use of PGMs for food safety analysis.This review introduces the basic detection principle of a PGM-based sensing strategy,which consists of three key factors:target recognition,signal transduction,and signal output.Representative studies of existing PGM-based sensing strategies combined with various signal amplification technologies(nanomaterial-loaded multienzyme labeling,nucleic acid reaction,DNAzyme catalysis,responsive nanomaterial encapsulation,and others)in the field of food safety detection are reviewed.Future perspectives and potential opportunities and challenges associated with PGMs in the field of food safety are discussed.Despite the need for complex sample preparation and the lack of standardization in the field,using PGMs in combination with signal amplification technology shows promise as a rapid and cost-effective method for food safety hazard analysis.

Revealing the contribution of basilar membrane's biological activity to the mechanism of the cochlear phonosensitive amplification

Explaining the mechanism of the cochlear active phonosensitive amplification has been a major problem in medicine.The basilar membrane(BM)is the key infrastructure.In 1960,Nobel Laureate von B′ek′esy first discovered BM's traveling wave motion.Since that time,BM's models only have considered the traveling wave but not the biological activity.Therefore,a new model considering changes of BM's stiffness in space and time is established based on the immersed boundary method to describe its biological activity.It not only reproduces the results of traveling wave motion but also explains the mechanization on the generation of traveling wave.An important discovery is that changes of BM's stiffness in space and time will cause the unstable global resonance,which will induce amplification of sounds in cochlea.An important inference is that biological activity shall be included in the application of mechanical principles to the analysis of life,which is the essential difference between biomechanics and general mechanics.

Stability and multistability of synchronization in networks of coupled phase oscillators

Coupled phase oscillators usually achieve synchronization as the coupling strength among oscillators is increased beyond a critical value. The stability of synchronous state remains an open issue. In this paper, we study the stability of the synchronous state in coupled phase oscillators. It is found that numerical integration of differential equations of coupled phase oscillators with a finite time step may induce desynchronization at strong couplings. The mechanism behind this instability is that numerical accumulated errors in simulations may trigger the loss of stability of the synchronous state.Desynchronization critical couplings are found to increase and diverge as a power law with decreasing the integral time step. Theoretical analysis supports the local stability of the synchronized state. Globally the emergence of synchronous state depends on the initial conditions. Other metastable ordered states such as twisted states can coexist with the synchronous mode. These twisted states keep locally stable on a sparse network but lose their stability when the network becomes dense.

Role of Ocean Dynamics in the Seasonal Hadley Cell:A Response to Idealized Arctic Amplification

How atmospheric and oceanic circulations respond to Arctic warming at different timescales are revealed with idealized numerical simulations.Induced by local forcing and feedback,Arctic warming appears and leads to sea-ice melting.Deep-water formation is inhibited,which weakens the Atlantic Meridional Overturning Circulation(AMOC).The flow and temperature in the upper layer does not respond to the AMOC decrease immediately,especially at mid-low latitudes.Thus,nearly uniform surface warming in mid-low latitudes enhances(decreases)the strength(width)of the Hadley cell(HC).With the smaller northward heat carried by the weaker AMOC,the Norwegian Sea cools significantly.With strong warming in Northern Hemisphere high latitudes,the long-term response triggers the“temperature-wind-gyre-temperature”cycle,leading to colder midlatitudes,resulting in strong subsidence and Ferrel cell enhancement,which drives the HC southward.With weaker warming in the tropics and stronger warming at high latitudes,there is a stronger HC with decreased width.A much warmer Southern Hemisphere appears due to a weaker AMOC that also pushes the HC southward.Our idealized model results suggest that the HC strengthens under both warming conditions,as tropical warming determines the strength of the HC convection.Second,extreme Arctic warming led by artificially reduced surface albedo decreases the meridional temperature gradient between high and low latitudes,which contracts the HC.Third,a warmer mid-high latitude in the Northern(Southern)Hemisphere due to surface albedo feedback(weakened AMOC)in our experiments pushes the HC northward(southward).In most seasons,the HC exhibits the same trend as that described above.

Mass-Oscillators as Information Memories of Action

In the theory of physical information, the physical phenomena of electromagnetism, quantum mechanics and gravity can be described by means of the action as information enclosed in four dimensional structures with oscillator properties, under the conditions of the Hamilton principle. The present report shows that it is also possible to simulate the behaviour of the mass under these conditions. As a result, among other things, the statements are obtained that the mass is stored virtual action;the rest frame of elementary objects and the inertia of matter are caused by the action stored in the mass oscillators.

The Frequency of the v-AKT Murine Thymoma Viral Oncogene Homologue 1 Gene Amplification among Sudanese Women with Ovarian Cancer: A Cross-Sectional Study

Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to the AKT family among Sudanese women with OC. The present study was conducted to detect the AKT1 gene amplification and its association with tumour types, grades, and ages among Sudanese women with OC, bearing in mind the ethnic variation. Methods: This institution-based study included 79 cases of women diagnosed with ovarian cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018. Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results: The mean age (±SD) of included women was 49.29 (±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11 (27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC (16.7%). High frequency was seen in women with low (26.3%;n = 10/28) rather than in higher (19.5%;n = 8/33) grade carcinoma, and in older (25.8%;n = 8/23) rather than younger (18.2%;n = 2/9) women. No significant association between AKT1 gene amplification and tumour types, grades, and ages of women was observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion: AKT1 gene amplification arises in around one-fifth of Sudanese women with ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and mucinous tumours types, and more frequently in low tumour grade and older women, but not to a statistically significant level. These outcomes sustenance previous studies suggesting that activated AKT genes have a vital role in OC progression and may offer a plan for targeted therapy and prognostic evaluation.