Trends and frontiers in signal amplification for aptamer-based tumor detection:A bibliometric analysis

BACKGROUND Malignant tumors are one of the leading causes of death worldwide,imposing a substantial economic and social burden.Early detection is the key to improving cure rates and reducing mortality rates,which requires the development of sensitive early detection technologies.Signal amplification techniques play a crucial role in aptamer-based early detection of tumors and are increasingly garnering attention from researchers.AIM To investigate the current research status,developmental trajectories,and hotspots in signal amplification for aptamer-based tumor detection through bibliometric analysis.METHODS English publications pertaining to signal amplification in aptamer-based tumor detection were retrieved from the Web of Science Core Collection database.VOSviewer and CiteSpace software were employed to analyze various information within this field,including countries,institutions,authors,co-cited authors,journals,co-cited journals,cited references,and keywords.RESULTS A total of 757 publications were included in this study.China accounted for 85.47%of all publications,with Nanjing University(China)emerging as the institution with the highest publication output.The most influential authors and journals were Hasanzadeh M.from Iran and"Biosensors and Bioelectronics",respectively.Exosomes and carcinoembryonic antigen(CEA)stood out as the most researched tumor-related molecules.Currently,the predominant signal amplification technique,nanomaterial,and signal transduction method were identified as hybridization chain reactions,gold nanoparticles,and electrochemical methods,respectively.Over the past 3 years,exosomes,CEA,electrochemical biosensors,and nanosheets have emerged as research hotspots,exhibiting a robust burst of intensity.CONCLUSION This study is the first bibliometric analysis of literature on signal amplification in aptamer-based tumor detection and elucidates the current status,hotspots,and prospective research directions within this realm.Additionally,it provides an important reference for researchers.

A Study of Radiation-Induced Telomere Instability Using Multiplex Ligation-Dependent Probe Amplification (MLPA)

The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.

Modified Sadowski formula-based model for the slope shape amplification effect under multistage slope blasting vibration

Blasting operations,which are crucial to open-pit mine production due to their simplicity and efficiency,require precise control through accurate vibration velocity calculations.The conventional Sadowski formula mainly focuses on blast center distance but neglects the amplification effect of blasting vibration waves by terraced terrain,from which the calculated blasting vibration velocities are smaller than the actual values,affecting the safety of the project.To address this issue,our model introduces the influences of slope and time into Sadowski formula to measure safety through blast vibration displacement.In the northern section of the open-pit quartz mine in Jinchang City,Gansu Province,China,the data of a continuous blasting slope project are referred to.Our findings reveal a noticeable vibration amplification effect during blasting when a multi-stage slope platform undergoes a sudden cross-sectional change near the upper overhanging surface.The amplification vibration coefficient increases with height,while vibration waves within rocks decrease from bottom to top.Conversely,platforms without distinct crosssectional changes exhibit no pronounced amplification during blasting.In addition,the vibration intensity decreases with distance as the rock height difference change propagates.The results obtained by the proposed blast vibration displacement equation incorporating slope shape influence closely agree with real-world scenarios.According to Pearson correlation coefficient(PPMCC)analysis,the average accuracy rate of our model is 88.84%,which exceeds the conventional Sadowski formula(46.92%).

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.

O(logN) Algorithm for Amplitude Amplification and O(logN) Algorithms for Amplitude Transfer in Grover’s Algorithm

Grovers algorithm is a category of quantum algorithms that can be applied to many problems through the exploitation of quantum parallelism. The Amplitude Amplification in Grovers algorithm is T = O(N). This paper introduces two new algorithms for Amplitude Amplification in Grovers algorithm with a time complexity of T = O(logN), aiming to improve efficiency in quantum computing. The difference between Grovers algorithm and our first algorithm is that the Amplitude Amplification ratio in Grovers algorithm is an arithmetic series and ours, a geometric one. Because our Amplitude Amplification ratios converge much faster, the time complexity is improved significantly. In our second algorithm, we introduced a new concept, Amplitude Transfer where the marked state is transferred to a new set of qubits such that the new qubit state is an eigenstate of measurable variables. When the new qubit quantum state is measured, with high probability, the correct solution will be obtained.

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.

Designing Primers for H5 and H7 Subtypes of Avian Influenza Virus and Multiplex RT-PCR Amplification

[Objective] The research aimed to design primers that are suitable for detecting H5 and H7 subtypes of avian influenza virus （AIV） ; [Method] DNAStar was used to analyze the homology of the sequences of H5 and H7 subtypes of AIV accessed in GenBank, and design primers（ by Primer Premier 5.0） on high homologous region of these sequences, and then amplified by RT-PCR. [Result] The multiplex RT-PCR amplification, agarose gel electrophoresis and sequencing results showed that the self-designed primers are successful for detecting AIV. [Conclusion] It is feasible to rapidly diagnose AIV through this method.

Application of Abnormal Touchdown PCR with High Degeneracy Primer in Amplification of Large-Family Genes

[Objective] The aim was to explore the special methods for amplification of large-family genes by using primers with high degeneracy.[Method] By using the primers with high degeneracy,conventional PCR,conventional touchdown PCR and the optimized abnormal touchdown PCR were respectively carried out to amplify the genomic DNA of Cyprinus carpio.[Result] Only one evident electrophoretic band and a few Sox genes were obtained by using normal PCR;no obvious electrophoretic band but dispersive product was obtained by normal touchdown PCR;ideal result was obtained by the abnormal touchdown PCR that three evident electrophoretic bands and much more Sox genes were amplified.[Conclusion] The research provided theoretical basis for the optimization and selection of PCR amplification conditions of the large-family genes.

Development of an One-step Reverse Transcription Loop-mediated Isothermal Amplification Method for Rapid Detection of Bovine Viral Diarrhea Virus

Objective] This study aimed to develop a reverse transcription loop-medi-ated isothermal amplification （RT-LAMP） method for detecting BVDV. [Method] Since gp48 gene of BVDV is among the most conserved regions, a set of four primers was designed to amplify six target sequences at the gp48 gene region for the RT-LAMP assay. The optimization of the RT-LAMP reaction was performed by evaluat-ing reaction temperature and reaction time. [Result] The RT-LAMP aasay was suc-cessful y conducted at 56 ℃ within 40 min under isothermal conditions, and the re-sults could be detected as ladder-like bands using agarose gel electrophoresis. The RT-LAMP assay is highly sensitive and able to detect 3.74 ×100 copies/μl of BVDV RNA, as no cross-reaction was observed with other viruses. [Conclusion] Overal , the newly established RT-LAMP assay indicates the potential application in both clinical diagnosis and field surveil ance of BVDV.

Establishment of Reverse-transcription Loopmediated Isothermal Amplification Method for Detection of Wheat Streak Mosaic Virus

A reverse-transcription loop-mediated isothermal amplification （RT-LAMP） method was established for the detection of wheat streak mosaic virus （WSMV）. Ac-cording to the conservative regions of the genes that encode the coat protein of WSMV, 2 pairs of primers were designed. Final y, the 1st pair of primers was select-ed through the specificity test. The sensitivity test showed the sensitivity of RT-LAMP method was 10 times higher than that of RT-PCR. In addition, the amplifica-tion of target gene could be judged visual y from the presence of fluorescence （cal-cein） in the final reaction system. The RT-LAMP method, established in this study, was rapid, easy, specific and sensitive. Moreover, it did not require sophisticated equip-ment. The RT-LAMP was suitable for the rapid detection of WSMV.

Chromosomal Localization of Genes bz1,bz2 in Maize by Using Ultra-sensitive FISH with Tyramide Signal Amplification(TSA-FISH)

It has been reported that endosperm undergoes programmed cell death (PCD) during maize kernel development.Both bz1 (bronze ) and bz2 are anthocyanin biosynthetic genes,and related to development of aleuronic layer of maize seeds.Tyramide signal amplification fluorescence in situ hybridization (TSA FISH) is a novel and high sensitive FISH technique,which is suitable for routine application in plant cytogenetic research.Using this technique,we physically mapped the bz1 gene onto the short arm of chromosome 9 and the long arm of chromosome 1;the percentage distances from centromere to hybridization site were 40.2,75.4 respectively,and the bz2 onto the long arm of chromosome 1 and the short arm of chromosome 5;the percentage distances from centromere to hybridization site were 21.6,15.3 separately.The TSA FISH techniques of small low copy DNA sequences for plants are discussed.

Laser Capture Microdissection Combined with RNA in vitro Linear Amplification Detecting the Relevant Genes of Bladder Cancer

Objective： Laser capture microdisection has become indispensable to the analysis of the difference of gene expression between human bladder transitional cell and bladder transitional cell carcinoma （BTCC）. However, to obtain sufficient RNA from laser-capture microdissected cells is quite difficult. The study was designed to determinc a feasible technical routine to isolate transitional cells from bladder membrane, separate carcinoma cclls from stromal cells and to amplify the RNA isolated from laser-capture microdissected cells. Methods： Bladder transitional cell were obtained from frozen sections of bladder membrane applying LCM, by the same token, BTCC cells from frozen sections of BTCC tissue. Then RNA was extracted and linearly amplified in vitro. The expression levels of β-actin in primary total RNA and amplified RNA were detected using RT-PCR. Results： That RNA integrity was good after LCM was confirmed by control experiment Ⅰ; By control experiment Ⅱ, the correlation between the number of LCM-shooting and RNA quantity undcr arranged conditions was preliminarily confirmed. About 0.5-2.5kb RNA fragments were obtained after RNA amplification and β-actin levels were integral. Conclusion： Laser capture microdissection combined with RNA linear amplification in vitro can be successfully applied to obtain pure objective cells for research. The integrity of the amplified RNA is good and can be employed in further research.

The Application of Reverse Transcription-loop-mediated Isothermal Amplification for the Rapid Detection of Maize Chlorotic Dwarf Virus

Maize chlorotic dwarf virus （MCDV） is a quarantine pest as approved by Chinese government. A rapid, sensitive and specific MCDV detection method using reverse transcription-loop-mediated isothermal amplification （RT-LAMP） was estab- lished in this study. Based on the sequence of MCDV coat protein coding gene, specific primers were designed and similar sensitivities were observed between RT- LAMP and RT-PCR, except that RT-LAMP was quicker, and the reaction could be finished within 1 h. In addition, the presence or absence of the fluorescent display in daylight allows naked easy detection of the amplification of MCDV genomic RNA using calcein. The RT-LAMP assay was applied successfully to detect MCDV in maize seeds, and the result by the addition of calcein was consistent with the result detected by the real time turbidimeter.

A panel of polymorphic microsatellites in the Blue Eared Pheasant (Crossoptilon auritum) developed by cross-species amplification

Polymorphic microsatellites are among the versatile genetic markers in molecular ecology studies. In contrast to de novo isolation of microsatellites from target species, cross-species amplification is a costeffective approach for a fast development of microsatellite markers from closely related taxa. In our study, we crossamplified a panel of polymorphic microsatellite markers for the Blue Eared Pheasant (Crossoptilon auritum), a species endemic to China of considerable conservation concern. We obtained 11 polymorphic microsatellite markers selected from 112 candidate loci, originally isolated from other Galliforme species. This panel of makers has shown moderate to high levels of polymorphism and include a Z-chromosomal linkage locus. We carried out preliminary analyses of parentage among captive individuals with a known pedigree using this new panel of microsatellites. Our results suggest that the high utility of these markers may be powerful tools for studies in conservation genetics of eared-pheasants and other endangered Galliforme species.

Efficiency of the motion amplification device with viscous dampers and its application in high-rise buildings

After nearly a decade of application and investigation, a motion amplification device with viscous dampers for energy dissipation has been recognized as an effective solution to mitigate wind or seismic excitation, especially for stiff structural systems. As a result of compensation of amplified motion, it has been proved that the efficiency of viscous damper largely depends on the motion amplification device configuration, particularly for device stiflhess. In this paper, a ＂scissor-jack＂ type of motion amplification device, called a ＂toggle brace damper＂ system, is studied. It is demonstrated that the efficiency of such a device reflected by its amplification factor is not merely a function of its geometric configuration, but is highly dependent on the support elements＇ stiffness as well, similar to the mechanism of a leverage arm. Accordingly, a mathematical model in terms of complex modulus of the viscous damper with consideration of the support brace＇s stiffness is established. The results indicate that the efficiency of the motion amplification device with viscous dampers significantly depends on the stiffness of the support elements. Other parameters, such as toggle brace configuration and damping values of the viscous damper, are studied and compared. As an application example, numerical analyses are conducted to study the dynamic performance of a 39-story office tower installed with toggle brace dampers constructed on soft soil in a reclaimed area, under a combined effect of the vortex shedding of an adjacent existing 52-story building and earthquakes. The results show that viscous dampers with a motion amplification system using a properly designed toggle brace device proved to be an effective solution to alleviate the external excitations.

Study of differential polymerase chain reaction of C-erbB-2 oncogene amplification in gastric cancer

AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.

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.

A note on near-field site amplification effects of ground motion from a radially inhomogeneous valley

To improve the understanding of the near-field soil and topographic amplification effects, an analytical solution by the authors for the scattering of plane SH waves by a radially inhomogeneous semi-cylindrical valley is extended to the case of a line source of cylindrical SH waves. Upon confirmation of its accuracy with past exact solutions for a homogeneous and an inhomogeneous semi-cylindrical valley under far-field plane SH waves, the extended solution is used to calculate the ground motion amplification factors for both the homogeneous and inhomogeneous valleys subjected to near-field waves. A comprehensive parametric study is conducted with respect to the location of the wave source, the dimensionless frequency of the incident waves, and the inhomogeneity degree of the covering soil layer. It is found that more amplifications and reductions of ground motions will occur within a certain range in and around the valley as the sources are located further. Consistent with the far-field case, it is confirmed that an increase of the degree of inhomogeneity of the covering soil layer generally amplifies the ground motions significantly.

Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy

Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis.Results: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P<0.001). Twenty-one out of 326 patients(6.4%) were identified as MET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.