Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an i...Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.展开更多
The kelp grouper (Epinephelus bruneus), belonging to one of the largest genera among the subfamily Epinephelinae, is a commercially important fish in Japan. There are limited data about the genomics of this species. T...The kelp grouper (Epinephelus bruneus), belonging to one of the largest genera among the subfamily Epinephelinae, is a commercially important fish in Japan. There are limited data about the genomics of this species. To provide tools for addressing both population genetics studies and gene mapping, dito pentanucleotide simple sequence repeat (SSR) markers were developed using 454 pyrosequencing. Among the 1466 SSR markers developed, 1244 primer sets produced strong PCR products, of which 905 (72.7%) were polymorphic in kelp grouper. Cross-species utility of the 905 polymorphic SSR markers was tested in four additional Epinephelinae species of Hyporthodus septemfasciatus, Plectropomus leopardus, Epinephelus lanceolatus and Epinephelus coioides. Results revealed that, respectively, 401 (44.3%), 136 (15.0%), 434 (49.0%) and 538 (59.4%) SSRs showed specific polymorphic products. Of these, 40 SSR markers (33 di-, 1 tri- and 6 tetra-nucleotides) showed polymorphism in all species tested. Additionally, three AGAT SSR motifs which accounted for 42.9% of the nondi-nucleotide markers were found in the 40 SSR markers. This indicates that the AGAT SSR motif has a high potential as a highly versatile SSR marker in grouper Epinephelinae. The SSR markers developed in this study can be employed to obtain reliable genetic variability estimates for groupers (Epinephelinae).展开更多
The theory of slow backward-wave amplifications is developed based on electron cyclotron maser （ECM） mechanism employing an initially rectilinear beam, A nonlinear evolution equation is derived to describe the elect...The theory of slow backward-wave amplifications is developed based on electron cyclotron maser （ECM） mechanism employing an initially rectilinear beam, A nonlinear evolution equation is derived to describe the electron energy. Numerical calculations show that the saturated interaction efficiency in this system may exceed 20~, and the saturated interaction length spans 3-6 centimeters. The distinctive interaction mechanism is promising for the design of compact backward microwave amplification devices, Numerical studies are also presented for the slow-wave ECM efficiency with inclusion of Gaussian beam electron velocity spread. It is shown that the velocity spread reduces the interaction e^ciency.展开更多
Thirty-two cases of ovarian carcinoma, two of normal ovaries, four of benign epithelial ovarian tumor, and three of borderline epithelial ovarian tumor were studied using Southern blot hybridization of DNA. In 15 of t...Thirty-two cases of ovarian carcinoma, two of normal ovaries, four of benign epithelial ovarian tumor, and three of borderline epithelial ovarian tumor were studied using Southern blot hybridization of DNA. In 15 of the 32 cases of ovarian carcinoma, peripheral lymphocytes were also studied. The amplification rate of C-myc, C-N-ras, C-Ki-ras and C-erbB-2 in ovarian carcinoma were 50%, 44%, 31% and 25% respectively. The amplification of C-Ki-ras and C-N-ras took place chiefly in cases of early stage and those of good differentiation. The amplification of C-N-ras was also found in cases of advanced stage. The amplifications of C-myc and C-erbB-2 were chiefly found in cases above stage Ⅲ and those of poor differentiation. A total of 83% of the patients who died were found to have amplifications of more than 2 proto-oncogenes, with which the amplification of C-erbB-2 was involved.展开更多
We compare different discreted DCF Raman amplifier configurations, including single-stage and dual-stage. The optimum design with respect to SNR degradation, compromise linear and nonlinear impairments.
Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
BACKGROUND Rhabdomyosarcoma(RMS)is a type of malignant tumor originating from rhabdomyocytes or mesenchymal cells differentiating into rhabdomyocytes.Hepatic pleomorphic RMS is a rare malignant liver tumor.Hepatic sar...BACKGROUND Rhabdomyosarcoma(RMS)is a type of malignant tumor originating from rhabdomyocytes or mesenchymal cells differentiating into rhabdomyocytes.Hepatic pleomorphic RMS is a rare malignant liver tumor.Hepatic sarcomatoid carcinoma is also a rare epithelial malignant tumor originating from the liver;it is characterized by the coexistence of both carcinomatous and sarcomatoid spindle cell components.CASE SUMMARY This paper reports a special case of an elderly woman whose initial liver puncture biopsy showed pleomorphic RMS.After chemotherapy with the vincristine+doxorubicin+cyclophosphamide regimen,the alpha-fetoprotein level increased significantly.Therefore,a second liver puncture was performed,the pathological result of which was hepatic sarcomatoid carcinoma.Next-generation sequencing revealed MET gene amplification with an average copy number of 9 in the tumor tissue;however,both fluorescence in situ hybridization and immunohistochemical tests were negative for MET amplification.The treatment regimen was adjusted to chemotherapy combined with immunotherapy;however,the disease progressed rapidly,and the overall survival was only 6 months.CONCLUSION By sharing the diagnosis and treatment process of this patient and reviewing the relevant literature,we aim to help clinicians enhance their understanding of two rare diseases,namely pleomorphic RMS and sarcomatoid carcinoma of the liver.展开更多
Global warming induced by increased CO_(2) has caused marked changes in the ocean.Previous estimates of ocean salinity change in response to global warming have considerable ambiguity,largely attributable to the diver...Global warming induced by increased CO_(2) has caused marked changes in the ocean.Previous estimates of ocean salinity change in response to global warming have considerable ambiguity,largely attributable to the diverse sensitivities of surface fluxes.This study utilizes data from the Flux-Anomaly-Forced Model Intercomparison Project to investigate how ocean salinity responds to perturbations of surface fluxes.The findings indicate the emergence of a sea surface salinity(SSS)dipole pattern predominantly in the North Atlantic and Pacific fresh pools,driven by surface flux perturbations.This results in an intensification of the“salty gets saltier and fresh gets fresher”SSS pattern across the global ocean.The spatial pattern amplification(PA)of SSS under global warming is estimated to be approximately 11.5%,with surface water flux perturbations being the most significant contributor to salinity PA,accounting for 8.1% of the change after 70 years in experiments since pre-industrial control(piControl).Notably,the zonal-depth distribution of salinity in the upper ocean exhibits lighter seawater above the denser water,with bowed isopycnals in the upper 400 m.This stable stratification inhibits vertical mixing of salinity and temperature.In response to the flux perturbations,there is a strong positive feedback due to consequent freshening.It is hypothesized that under global warming,an SSS amplification of 7.2%/℃ and a mixed-layer depth amplification of 12.5%/℃ will occur in the global ocean.It suggests that the salinity effect can exert a more stable ocean to hinder the downward transfer of heat,which provides positive feedback to future global warming.展开更多
BACKGROUND Well-differentiated small bowel mesenteric liposarcoma(LPS)is rare,with high malignancy,poor prognosis,and high preponderance to local recurrence.CASE SUMMARY Here we described a 71-year-old male,who compla...BACKGROUND Well-differentiated small bowel mesenteric liposarcoma(LPS)is rare,with high malignancy,poor prognosis,and high preponderance to local recurrence.CASE SUMMARY Here we described a 71-year-old male,who complains of persistent abdominal distension for a month.The clinical manifestation is a huge abdominal mass occupying almost the entire abdomen.Physical examination indicated palpable massive mass in the abdomen,hard texture,indefinable boundary,poor mobility.The abdominal enhanced computed tomography at another hospital scan showed multiple abdominal masses originating from the small bowel mesentery.Abdominal and pelvic magnetic resonance imaging at our hospital showed multiple masses in the abdominal and pelvic cavities,indicating that the tumor originated from the mesentery or peritoneum.Results of exploratory laparotomy indicated that the tremendous mass primarily results from the mesentery of the small intestine,occupying the entire abdominal cavity in a polymorphic and lobulated shape.The patient underwent complete surgical resection of the tumor,and the weight of the tumor was approximately 11 kg.The histopathological examination of the resected specimens confirmed the diagnosis of well-differentiated LPS of the small bowel mesentery.CONCLUSION Completed surgical resection was cornerstone,and histopathological and molecular confirmations were crucial.The necessity of adjuvant therapy should be phrased as a potential consideration to improve patient’s survival time.展开更多
High coherence of the laser is indispensable light sources in modern long or short-distance imaging systems, because the high coherence leads to coherent artifacts such as speckle that corrupt image formation. To deli...High coherence of the laser is indispensable light sources in modern long or short-distance imaging systems, because the high coherence leads to coherent artifacts such as speckle that corrupt image formation. To deliver low coherence pulses in fiber amplifiers, we utilize the superluminescent pulsed light with broad bandwidth, nonlongitudinal mode structure and chaotic mode phase as the seed source of the cascaded fiber amplifiers. The influence of fiber superluminescent pulse amplification(SPA) on the limitations of the performance is analyzed. A review of our research results for SPA in the fibers are present, including the nonlinear theories of this low coherent light sources, i.e., self-focusing(SF), stimulated Raman scattering(SRS) and self-phase modulation(SPM) effects, and the experiment results of the nanosecond pulses with peak power as high as 4.8 MW and pulse energy as much as 55 mJ. To improve the brightness of SPA light in the future work, we introduce our novel evaluation term and a more reasonable criterion, which is denoted by a new parameter of brightness factor for active large mode area fiber designs. A core-doped active large pitch fiber with a core diameter of 190 μm and a mode-field diameter of 180 μm is designed by this method. The designed fiber allows near diffracted limited beam quality operation, and it can achieve 100 mJ pulse energy and 540 W average power by analyzing the mode coupling effects induced by heat.展开更多
With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a c...With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.展开更多
Bedding parallel stepped rock slopes exist widely in nature and are used in slope engineering.They are characterized by complex topography and geological structure and are vulnerable to shattering under strong earthqu...Bedding parallel stepped rock slopes exist widely in nature and are used in slope engineering.They are characterized by complex topography and geological structure and are vulnerable to shattering under strong earthquakes.However,no previous studies have assessed the mechanisms underlying seismic failure in rock slopes.In this study,large-scale shaking table tests and numerical simulations were conducted to delineate the seismic failure mechanism in terms of acceleration,displacement,and earth pressure responses combined with shattering failure phenomena.The results reveal that acceleration response mutations usually occur within weak interlayers owing to their inferior performance,and these mutations may transform into potential sliding surfaces,thereby intensifying the nonlinear seismic response characteristics.Cumulative permanent displacements at the internal corners of the berms can induce quasi-rigid displacements at the external corners,leading to greater permanent displacements at the internal corners.Therefore,the internal corners are identified as the most susceptible parts of the slope.In addition,the concept of baseline offset was utilized to explain the mechanism of earth pressure responses,and the result indicates that residual earth pressures at the internal corners play a dominant role in causing deformation or shattering damage.Four evolutionary deformation phases characterize the processes of seismic responses and shattering failure of the bedding parallel stepped rock slope,i.e.the formation of tensile cracks at the internal corners of the berm,expansion of tensile cracks and bedding surface dislocation,development of vertical tensile cracks at the rear edge,and rock mass slipping leading to slope instability.Overall,this study provides a scientific basis for the seismic design of engineering slopes and offers valuable insights for further studies on preventing seismic disasters in bedding parallel stepped rock slopes.展开更多
A glacier hazard chain can form a long-runout mass flow and generate a large flood,affecting downstream areas hundreds of kilometers away from the initiating hazard site.This study focuses on the Yarlung Zangbo Daxiag...A glacier hazard chain can form a long-runout mass flow and generate a large flood,affecting downstream areas hundreds of kilometers away from the initiating hazard site.This study focuses on the Yarlung Zangbo Daxiagu.The objective is to address two key unresolved issues:the evolution of detached glacier materials into debris flows or debris floods and the amplification of the impact range and threats.A comprehensive framework is developed that considers the impacts of near-field and far-field hazards.Numerical modeling,remote sensing,and field investigations were integrated to understand the interactions,transformations,and amplifications of hazards in the glacier hazard chain.The results indicate that extensive,nearly saturated sediments on the glacier valley floor,when entrained,amplify the magnitude of the mass flow.The topography plays a crucial role.When the valley outlet is perpendicular to the river course,topographic obstacles cause immediate halting,resulting in the formation of high barrier dams.Conversely,when the glacier valley aligns nearly parallel to the river course,the mass flow can travel a much longer distance upon entering the river,causing an enlarged affected area.The barrier dams can breach rapidly,causing breaching floods that amplify the downstream impact from several kilometers to hundreds of kilometers.Our analysis reveals that the overall impacts remain spatially limited.Specifically,downstream areas along the Yarlung Zangbo-Brahmaputra River are unlikely to face greater threats from the upstream floods than local monsoon floods.Our findings provide the foundation for the management of glacier hazard chains.展开更多
Soil DNA extraction,such as microbial community analysis and gene drift detection,is an important basis for multiple analyses in different fields.Nevertheless,the soil DNA extraction methods for field detection are st...Soil DNA extraction,such as microbial community analysis and gene drift detection,is an important basis for multiple analyses in different fields.Nevertheless,the soil DNA extraction methods for field detection are still lacking.This study established a rapid soil DNA extraction(RSDE)method that can be used in field detection.In this method,we first utilized the optimized lysate to isolate DNA from soil and then used a filtration membrane and a DNA adsorption membrane to purify the DNA via the column method.Moreover,we used the pressure from the syringe instead of the conventional centrifugal force of the centrifuge to assist the sample filtration,resulting in very low requirements for this method,with an extraction time of less than 20 min.Furthermore,we demonstrated that the RSDE method was applicable for DNA extraction from different types of soils,with the demand for soil samples as low as 0.1 g and that the amount of obtained DNA was,to some extent,greater than that obtained by a commercial kit.Further analysis revealed that this extracted genomic DNA can be used directly for polymerase chain reaction(PCR)analysis,including ordinary PCR,real-time fluorescent quantitative PCR,and recombinase polymerase amplification(RPA)-CRISPR/Cas12a visual assays.In addition,we demonstrated that this method can be used to extract DNA from residual plant roots in addition to soil microbes,which lays a foundation for the comprehensive analysis of soil plants and microorganisms.In summary,the RSDE method proposed in this study may have wide application prospects.展开更多
In this paper,we have mainly studied the amplification effect of thulium-doped fiber amplifier(TDFA)at 2µm,and compared different amplification effects of the one-stage TDFA,two-stage TDFA and three-stage TDFA at...In this paper,we have mainly studied the amplification effect of thulium-doped fiber amplifier(TDFA)at 2µm,and compared different amplification effects of the one-stage TDFA,two-stage TDFA and three-stage TDFA at proper conditions.The simulation results show that within the effective threshold,with the increase of the pump power,the amplification effect of the optical amplifier improves,but the signal-to-noise ratio(SNR)of the output signal decreases,in order to balance the gain benefit and noise coefficient of TDFA,we can use a multi-stage amplification structure.Three-stage backward-pumped series 2.06µm TDFA,whose slope efficiency can achieve 11%at certain condition.At 5.2 W pump power,the output signal gain of 2µm TDFA exceeds 20 dB,and the output SNR is higher than 32 dB.In addition,the effect of the optimum length of thulium-doped fiber on the amplification performance of 2µm TDFA is also analyzed in this paper.These simulation results are important for the experiment and design of 2µm TDFA.展开更多
The seismic design forces of nonstructural components(NSCs)in buildings are closely related to floor acceleration response amplification.To investigate the differences in acceleration responses of structures with diff...The seismic design forces of nonstructural components(NSCs)in buildings are closely related to floor acceleration response amplification.To investigate the differences in acceleration responses of structures with different structural types,fundamental periods,and seismic design levels,56 reinforced concrete and steel structures with fundamental periods ranging from 0.37 s to 5.68 s were selected.For each structure,100 sets of earthquake motions were used as inputs for elastic time history analysis.Based on the resulting 26,500 sets of floor acceleration response data,the amplification rules of peak floor acceleration/peak ground acceleration(PFA/PGA)along the height of various structures and the corresponding floor response spectrum characteristics were studied.The nonlinear changes of PFA/PGA along the height of long period structures were compared with the codes of different countries.Moreover,more suitable prediction equations were proposed based on the structural characteristics.Finally,to solve the issue that existing research still cannot accurately reflect the acceleration amplification coefficient of NSCs with different dynamic characteristics in main structures with different periods,a normalized floor response spectrum is proposed that can simultaneously consider the effects of input ground motion characteristics and the main structure,which can be better used in the seismic design of NSCs.展开更多
Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivi...Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivity to external conditions.However,achieving enhanced amplification or decision-making necessitates the incorporation of multiple strands,thereby increasing the risk of contamination.Recent advancements have led to the development of CRISPR-Cas-based DNA circuits.These systems aim to simplify the complexity associated with conventional circuits,mitigate contamination risks,and enable more substantial amplification or decision-making capabilities.Here,the review article centers on current strategies of CRISPR-Cas(Cas9,Cas12a,Cas13a)system-assisted circuits in amplification and decisionmaking,and assesses their tendencies and limitations in amplification circuits and decision-making circuits.Furthermore,we discuss the challenges of CRISPR-Cas in circuits and propose prospects that will contribute to constructing more efficient and diverse CRISPR-Cas-based DNA functional circuits.展开更多
Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low c...Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low cost,high efficiency,and high portability;however,the analysis of results tends to rely on bulky and sophisticated instruments,and this limits its applications.In this work,we developed a Raspberry Pi camera-based biomarker detection device based on microfluidic technology and digital image colorimetry.For highly sensitive biomarker detection on microfluidic chips,we propose a three-step signal-amplification colorimetric detection strategy consisting of:(1)the release of Ag^(+)ions from silver nanoparticles,(2)Ag^(+)-inhibited urea hydrolysis colorimetry,and(3)microscopic lens magnification.For efficient evaluation of results,we employed an RGB image-processing system to quantitatively analyze color images captured by the Raspberry Pi camera.Further,we tested the functionality of the device with procalcitonin(PCT)in phosphate-buffered saline,plasma,and serum to simulate clinical situations.We determined the limit of detection as 1 ng/ml,and a good linear relationship was established between PCT concentration and color intensity within the detection range 1–10 ng/ml.Importantly,only a relatively short detection time(40 min)was required in all three environments.The results demonstrate the great potential of this device for biomarker detection and facilitating biomedical research.展开更多
Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence i...Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence immunoassay system was designed.We encapsulated carbon dots with a high fluorescence quantum yield(QY=92.5%)inside silicon nanocapsules to serve as fluorescent markers.These markers were then integrated with the streptavidin(SA)-biotin biomagnification system and immunomagnetic separation technology for the sensitive detection of GFAP.Based on the signal cascade amplification effect of the silicon nanocapsules and SA-biotin,the fluorescence signal of the SA-biotin-modified immunofluorescence nanocapsules increased 3.6-fold compared to the carbon dot-based immunoprobe.The fluorescence immunoassay system was constructed for GFAP using SA-biotin-modified immunocapsules as the sensing probe and immunomagnetic nanoparticles as the immunorecognition probe.The fluorescence immunoassay system can specifically and ultra-sensitively quantify GFAP in blood samples,with a detection range of 10 pg/mL–10 ng/mL and detection limits of 3.2 pg/mL(serum)and 3.6 pg/mL(plasma).Moreover,the fluorescence immunoassay system exhibited prominent recoveries of 99.4%–100.4%(phosphate buffered saline),96%–102.6%(serum),and 93.2%–110.2%(plasma),with favorable specificity and excellent stabilization.The novel fluorescence immunoassay system provides a new approach to the clinical analysis of GFAP and may serve as a potential tool for screening and diagnosing TBI.展开更多
Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitori...Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.展开更多
文摘Three genetic mechanisms activate oncogenes in human neoplasms: 1) mutations, 2) gene amplification, and 3) chromosome rearrangements. These mechanisms result in either an alteration of protooncogene structure or an increase in protooncogene expression. The role of epigenetic aberrancies in carcinogenesis has been described earlier however to clinicians, the biological implications of epigenetic therapies to prevent cancer and the mechanisms involved have been a mystery. Furthermore, there is no biomarker suggested to track the carcinogenesis steps long before cancer develops, and this has caused a significant lack of proactive and preventive measures to be taken as all recommendations in preventive oncology are either deficiently and blindly made or through screening methods which are too late in the game. Here we explored a very different approach by applying our deepest understanding of epigenetics and carcinogenesis and even further we developed a framework where our clinical findings could translate to the research and vice versa by generating advanced and novel hypotheses on “how we get cancer”, by exploring the relation between the host and the tumor cells in a way no one had perceived before. The role of specific cancer stem cell pathways is dissected and how to inhibit each of these initiators using multitargeted epigenetic therapies and off-label medications are explained. We should admit that without considering this sophisticated amazing biological network, cancer will remain an unsolved challenge. Further, we were able to solve this unsolved puzzle by bridging the gap from a hypothetical point of view/hypothesis to possibilities that explain the clinical findings we had observed, and conclude that such an approach can completely change the way practitioners are treating cancer.
文摘The kelp grouper (Epinephelus bruneus), belonging to one of the largest genera among the subfamily Epinephelinae, is a commercially important fish in Japan. There are limited data about the genomics of this species. To provide tools for addressing both population genetics studies and gene mapping, dito pentanucleotide simple sequence repeat (SSR) markers were developed using 454 pyrosequencing. Among the 1466 SSR markers developed, 1244 primer sets produced strong PCR products, of which 905 (72.7%) were polymorphic in kelp grouper. Cross-species utility of the 905 polymorphic SSR markers was tested in four additional Epinephelinae species of Hyporthodus septemfasciatus, Plectropomus leopardus, Epinephelus lanceolatus and Epinephelus coioides. Results revealed that, respectively, 401 (44.3%), 136 (15.0%), 434 (49.0%) and 538 (59.4%) SSRs showed specific polymorphic products. Of these, 40 SSR markers (33 di-, 1 tri- and 6 tetra-nucleotides) showed polymorphism in all species tested. Additionally, three AGAT SSR motifs which accounted for 42.9% of the nondi-nucleotide markers were found in the 40 SSR markers. This indicates that the AGAT SSR motif has a high potential as a highly versatile SSR marker in grouper Epinephelinae. The SSR markers developed in this study can be employed to obtain reliable genetic variability estimates for groupers (Epinephelinae).
基金supported by National Natural Science Foundation of China(Nos.11275007 and 11175023)the Program for Liaoning Excellent Talents in University(LJQ2012098)
文摘The theory of slow backward-wave amplifications is developed based on electron cyclotron maser （ECM） mechanism employing an initially rectilinear beam, A nonlinear evolution equation is derived to describe the electron energy. Numerical calculations show that the saturated interaction efficiency in this system may exceed 20~, and the saturated interaction length spans 3-6 centimeters. The distinctive interaction mechanism is promising for the design of compact backward microwave amplification devices, Numerical studies are also presented for the slow-wave ECM efficiency with inclusion of Gaussian beam electron velocity spread. It is shown that the velocity spread reduces the interaction e^ciency.
文摘Thirty-two cases of ovarian carcinoma, two of normal ovaries, four of benign epithelial ovarian tumor, and three of borderline epithelial ovarian tumor were studied using Southern blot hybridization of DNA. In 15 of the 32 cases of ovarian carcinoma, peripheral lymphocytes were also studied. The amplification rate of C-myc, C-N-ras, C-Ki-ras and C-erbB-2 in ovarian carcinoma were 50%, 44%, 31% and 25% respectively. The amplification of C-Ki-ras and C-N-ras took place chiefly in cases of early stage and those of good differentiation. The amplification of C-N-ras was also found in cases of advanced stage. The amplifications of C-myc and C-erbB-2 were chiefly found in cases above stage Ⅲ and those of poor differentiation. A total of 83% of the patients who died were found to have amplifications of more than 2 proto-oncogenes, with which the amplification of C-erbB-2 was involved.
文摘We compare different discreted DCF Raman amplifier configurations, including single-stage and dual-stage. The optimum design with respect to SNR degradation, compromise linear and nonlinear impairments.
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
基金Supported by Shaanxi Provincial Natural Science Basic Research Program,No.2020JQ-951.
文摘BACKGROUND Rhabdomyosarcoma(RMS)is a type of malignant tumor originating from rhabdomyocytes or mesenchymal cells differentiating into rhabdomyocytes.Hepatic pleomorphic RMS is a rare malignant liver tumor.Hepatic sarcomatoid carcinoma is also a rare epithelial malignant tumor originating from the liver;it is characterized by the coexistence of both carcinomatous and sarcomatoid spindle cell components.CASE SUMMARY This paper reports a special case of an elderly woman whose initial liver puncture biopsy showed pleomorphic RMS.After chemotherapy with the vincristine+doxorubicin+cyclophosphamide regimen,the alpha-fetoprotein level increased significantly.Therefore,a second liver puncture was performed,the pathological result of which was hepatic sarcomatoid carcinoma.Next-generation sequencing revealed MET gene amplification with an average copy number of 9 in the tumor tissue;however,both fluorescence in situ hybridization and immunohistochemical tests were negative for MET amplification.The treatment regimen was adjusted to chemotherapy combined with immunotherapy;however,the disease progressed rapidly,and the overall survival was only 6 months.CONCLUSION By sharing the diagnosis and treatment process of this patient and reviewing the relevant literature,we aim to help clinicians enhance their understanding of two rare diseases,namely pleomorphic RMS and sarcomatoid carcinoma of the liver.
基金supported by the Laoshan Laboratory[grant number LSKJ202202403]the National Natural Science Foundation of China[grant number 42030410]+1 种基金additionally supported by the Startup Foundation for Introducing Talent of NUISTJiangsu Innovation Research Group[grant number JSSCTD202346]。
文摘Global warming induced by increased CO_(2) has caused marked changes in the ocean.Previous estimates of ocean salinity change in response to global warming have considerable ambiguity,largely attributable to the diverse sensitivities of surface fluxes.This study utilizes data from the Flux-Anomaly-Forced Model Intercomparison Project to investigate how ocean salinity responds to perturbations of surface fluxes.The findings indicate the emergence of a sea surface salinity(SSS)dipole pattern predominantly in the North Atlantic and Pacific fresh pools,driven by surface flux perturbations.This results in an intensification of the“salty gets saltier and fresh gets fresher”SSS pattern across the global ocean.The spatial pattern amplification(PA)of SSS under global warming is estimated to be approximately 11.5%,with surface water flux perturbations being the most significant contributor to salinity PA,accounting for 8.1% of the change after 70 years in experiments since pre-industrial control(piControl).Notably,the zonal-depth distribution of salinity in the upper ocean exhibits lighter seawater above the denser water,with bowed isopycnals in the upper 400 m.This stable stratification inhibits vertical mixing of salinity and temperature.In response to the flux perturbations,there is a strong positive feedback due to consequent freshening.It is hypothesized that under global warming,an SSS amplification of 7.2%/℃ and a mixed-layer depth amplification of 12.5%/℃ will occur in the global ocean.It suggests that the salinity effect can exert a more stable ocean to hinder the downward transfer of heat,which provides positive feedback to future global warming.
文摘BACKGROUND Well-differentiated small bowel mesenteric liposarcoma(LPS)is rare,with high malignancy,poor prognosis,and high preponderance to local recurrence.CASE SUMMARY Here we described a 71-year-old male,who complains of persistent abdominal distension for a month.The clinical manifestation is a huge abdominal mass occupying almost the entire abdomen.Physical examination indicated palpable massive mass in the abdomen,hard texture,indefinable boundary,poor mobility.The abdominal enhanced computed tomography at another hospital scan showed multiple abdominal masses originating from the small bowel mesentery.Abdominal and pelvic magnetic resonance imaging at our hospital showed multiple masses in the abdominal and pelvic cavities,indicating that the tumor originated from the mesentery or peritoneum.Results of exploratory laparotomy indicated that the tremendous mass primarily results from the mesentery of the small intestine,occupying the entire abdominal cavity in a polymorphic and lobulated shape.The patient underwent complete surgical resection of the tumor,and the weight of the tumor was approximately 11 kg.The histopathological examination of the resected specimens confirmed the diagnosis of well-differentiated LPS of the small bowel mesentery.CONCLUSION Completed surgical resection was cornerstone,and histopathological and molecular confirmations were crucial.The necessity of adjuvant therapy should be phrased as a potential consideration to improve patient’s survival time.
基金supported by the National High Technology Research and Development Program of Chinathe National Natural Science Foundation of China (No.61475081)the State Key Laboratory of Tribology, Tsinghua University (No.SKLT2014B09)
文摘High coherence of the laser is indispensable light sources in modern long or short-distance imaging systems, because the high coherence leads to coherent artifacts such as speckle that corrupt image formation. To deliver low coherence pulses in fiber amplifiers, we utilize the superluminescent pulsed light with broad bandwidth, nonlongitudinal mode structure and chaotic mode phase as the seed source of the cascaded fiber amplifiers. The influence of fiber superluminescent pulse amplification(SPA) on the limitations of the performance is analyzed. A review of our research results for SPA in the fibers are present, including the nonlinear theories of this low coherent light sources, i.e., self-focusing(SF), stimulated Raman scattering(SRS) and self-phase modulation(SPM) effects, and the experiment results of the nanosecond pulses with peak power as high as 4.8 MW and pulse energy as much as 55 mJ. To improve the brightness of SPA light in the future work, we introduce our novel evaluation term and a more reasonable criterion, which is denoted by a new parameter of brightness factor for active large mode area fiber designs. A core-doped active large pitch fiber with a core diameter of 190 μm and a mode-field diameter of 180 μm is designed by this method. The designed fiber allows near diffracted limited beam quality operation, and it can achieve 100 mJ pulse energy and 540 W average power by analyzing the mode coupling effects induced by heat.
基金the Experimental Technology Research Project of Zhejiang University(SYB202138)National Natural Science Foundation of China(32000195)。
文摘With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.
基金supported by the National Natural Science Foundation of China (Grant No.52108361)the Sichuan Science and Technology Program of China (Grant No.2023YFS0436)the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Independent Research Project (Grant No.SKLGP2022Z015).
文摘Bedding parallel stepped rock slopes exist widely in nature and are used in slope engineering.They are characterized by complex topography and geological structure and are vulnerable to shattering under strong earthquakes.However,no previous studies have assessed the mechanisms underlying seismic failure in rock slopes.In this study,large-scale shaking table tests and numerical simulations were conducted to delineate the seismic failure mechanism in terms of acceleration,displacement,and earth pressure responses combined with shattering failure phenomena.The results reveal that acceleration response mutations usually occur within weak interlayers owing to their inferior performance,and these mutations may transform into potential sliding surfaces,thereby intensifying the nonlinear seismic response characteristics.Cumulative permanent displacements at the internal corners of the berms can induce quasi-rigid displacements at the external corners,leading to greater permanent displacements at the internal corners.Therefore,the internal corners are identified as the most susceptible parts of the slope.In addition,the concept of baseline offset was utilized to explain the mechanism of earth pressure responses,and the result indicates that residual earth pressures at the internal corners play a dominant role in causing deformation or shattering damage.Four evolutionary deformation phases characterize the processes of seismic responses and shattering failure of the bedding parallel stepped rock slope,i.e.the formation of tensile cracks at the internal corners of the berm,expansion of tensile cracks and bedding surface dislocation,development of vertical tensile cracks at the rear edge,and rock mass slipping leading to slope instability.Overall,this study provides a scientific basis for the seismic design of engineering slopes and offers valuable insights for further studies on preventing seismic disasters in bedding parallel stepped rock slopes.
基金support from the National Natural Science Foundation of China(U20A20112,42061160480,42377196,and 52479095)the NSFC/RGC Joint Research Scheme(42061160480 and N_HKUST620/20)+1 种基金the Research Grants Council of the Hong Kong SAR Government(16203720,T22-606/23-R,and JRFS25266S09)the Project of Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone(HZQB-KCZYB-2020083)。
文摘A glacier hazard chain can form a long-runout mass flow and generate a large flood,affecting downstream areas hundreds of kilometers away from the initiating hazard site.This study focuses on the Yarlung Zangbo Daxiagu.The objective is to address two key unresolved issues:the evolution of detached glacier materials into debris flows or debris floods and the amplification of the impact range and threats.A comprehensive framework is developed that considers the impacts of near-field and far-field hazards.Numerical modeling,remote sensing,and field investigations were integrated to understand the interactions,transformations,and amplifications of hazards in the glacier hazard chain.The results indicate that extensive,nearly saturated sediments on the glacier valley floor,when entrained,amplify the magnitude of the mass flow.The topography plays a crucial role.When the valley outlet is perpendicular to the river course,topographic obstacles cause immediate halting,resulting in the formation of high barrier dams.Conversely,when the glacier valley aligns nearly parallel to the river course,the mass flow can travel a much longer distance upon entering the river,causing an enlarged affected area.The barrier dams can breach rapidly,causing breaching floods that amplify the downstream impact from several kilometers to hundreds of kilometers.Our analysis reveals that the overall impacts remain spatially limited.Specifically,downstream areas along the Yarlung Zangbo-Brahmaputra River are unlikely to face greater threats from the upstream floods than local monsoon floods.Our findings provide the foundation for the management of glacier hazard chains.
基金the Experimental Technology Research Project of Zhejiang University(SYB202138)National Natural Science Foundation of China(32000195).
文摘Soil DNA extraction,such as microbial community analysis and gene drift detection,is an important basis for multiple analyses in different fields.Nevertheless,the soil DNA extraction methods for field detection are still lacking.This study established a rapid soil DNA extraction(RSDE)method that can be used in field detection.In this method,we first utilized the optimized lysate to isolate DNA from soil and then used a filtration membrane and a DNA adsorption membrane to purify the DNA via the column method.Moreover,we used the pressure from the syringe instead of the conventional centrifugal force of the centrifuge to assist the sample filtration,resulting in very low requirements for this method,with an extraction time of less than 20 min.Furthermore,we demonstrated that the RSDE method was applicable for DNA extraction from different types of soils,with the demand for soil samples as low as 0.1 g and that the amount of obtained DNA was,to some extent,greater than that obtained by a commercial kit.Further analysis revealed that this extracted genomic DNA can be used directly for polymerase chain reaction(PCR)analysis,including ordinary PCR,real-time fluorescent quantitative PCR,and recombinase polymerase amplification(RPA)-CRISPR/Cas12a visual assays.In addition,we demonstrated that this method can be used to extract DNA from residual plant roots in addition to soil microbes,which lays a foundation for the comprehensive analysis of soil plants and microorganisms.In summary,the RSDE method proposed in this study may have wide application prospects.
基金supported by the Natural Science Foundation of Guangdong Province(Nos.2023A1515010093)the Shenzhen Fundamental Research Program(Nos.JCYJ20220809170611004,20231121110828001 and 20231121113641002)the Taipei University of Technology-Shenzhen University Joint Research Program(No.2024001).
文摘In this paper,we have mainly studied the amplification effect of thulium-doped fiber amplifier(TDFA)at 2µm,and compared different amplification effects of the one-stage TDFA,two-stage TDFA and three-stage TDFA at proper conditions.The simulation results show that within the effective threshold,with the increase of the pump power,the amplification effect of the optical amplifier improves,but the signal-to-noise ratio(SNR)of the output signal decreases,in order to balance the gain benefit and noise coefficient of TDFA,we can use a multi-stage amplification structure.Three-stage backward-pumped series 2.06µm TDFA,whose slope efficiency can achieve 11%at certain condition.At 5.2 W pump power,the output signal gain of 2µm TDFA exceeds 20 dB,and the output SNR is higher than 32 dB.In addition,the effect of the optimum length of thulium-doped fiber on the amplification performance of 2µm TDFA is also analyzed in this paper.These simulation results are important for the experiment and design of 2µm TDFA.
基金Natural Science Foundation of China under Grant Nos.52078471,52078472 and 52208509National Key Research and Development Plan of China under Grant No.2019YFE0112700+2 种基金Natural Science Foundation of Heilongjiang Province under Grant No.LH2022E121Special Project for Basic Scientific Research Business Expenses of the Institute of Engineering Mechanics,China Earthquake Administration under Grant No.2022C04Director’s Fund Director’s Fund of Earthquake Agency of Inner Mongolia Autonomous Region under Grant No.2023MS10。
文摘The seismic design forces of nonstructural components(NSCs)in buildings are closely related to floor acceleration response amplification.To investigate the differences in acceleration responses of structures with different structural types,fundamental periods,and seismic design levels,56 reinforced concrete and steel structures with fundamental periods ranging from 0.37 s to 5.68 s were selected.For each structure,100 sets of earthquake motions were used as inputs for elastic time history analysis.Based on the resulting 26,500 sets of floor acceleration response data,the amplification rules of peak floor acceleration/peak ground acceleration(PFA/PGA)along the height of various structures and the corresponding floor response spectrum characteristics were studied.The nonlinear changes of PFA/PGA along the height of long period structures were compared with the codes of different countries.Moreover,more suitable prediction equations were proposed based on the structural characteristics.Finally,to solve the issue that existing research still cannot accurately reflect the acceleration amplification coefficient of NSCs with different dynamic characteristics in main structures with different periods,a normalized floor response spectrum is proposed that can simultaneously consider the effects of input ground motion characteristics and the main structure,which can be better used in the seismic design of NSCs.
基金financially supported by the National Natural Science Foundation of China (Nos. 82172372 and 82260290)the Opening Research Fund of State Key Laboratory of Digital Medical Engineering (No. 2023-M04)
文摘Strand displacement-based DNA circuits have emerged as highly effective tools for molecular computation,serving purposes of amplification or decision-making.They are favored for their inherent occurrence and sensitivity to external conditions.However,achieving enhanced amplification or decision-making necessitates the incorporation of multiple strands,thereby increasing the risk of contamination.Recent advancements have led to the development of CRISPR-Cas-based DNA circuits.These systems aim to simplify the complexity associated with conventional circuits,mitigate contamination risks,and enable more substantial amplification or decision-making capabilities.Here,the review article centers on current strategies of CRISPR-Cas(Cas9,Cas12a,Cas13a)system-assisted circuits in amplification and decisionmaking,and assesses their tendencies and limitations in amplification circuits and decision-making circuits.Furthermore,we discuss the challenges of CRISPR-Cas in circuits and propose prospects that will contribute to constructing more efficient and diverse CRISPR-Cas-based DNA functional circuits.
基金supported by the National Key Research and Development Program of China(Grant Nos.2023YFA0915200 and 2023YFA0915204)Outstanding Young Scientist in Shandong Province(Grant No.ZR2024YQ064)+4 种基金Shandong Province Science and Technology Small and Medium Enterprises Innovation Capacity Improvement Project(Grant No.2024TSGC008)Shandong Provincial Key Research and Development Project(Grant Nos.2020CXGC011304 and 2022CXGC020206)Taishan Scholar Foundation of Shandong Province(Grant No.tsqn202408256)the Major Innovation Project for the Science Education Industry Integration Pilot Project of Qilu University of Technology(Shandong Academy of Sciences)(Grant No.2023JBZ03)Shanghai Science and Technology Development Funds(Grant No.23J21900100).
文摘Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low cost,high efficiency,and high portability;however,the analysis of results tends to rely on bulky and sophisticated instruments,and this limits its applications.In this work,we developed a Raspberry Pi camera-based biomarker detection device based on microfluidic technology and digital image colorimetry.For highly sensitive biomarker detection on microfluidic chips,we propose a three-step signal-amplification colorimetric detection strategy consisting of:(1)the release of Ag^(+)ions from silver nanoparticles,(2)Ag^(+)-inhibited urea hydrolysis colorimetry,and(3)microscopic lens magnification.For efficient evaluation of results,we employed an RGB image-processing system to quantitatively analyze color images captured by the Raspberry Pi camera.Further,we tested the functionality of the device with procalcitonin(PCT)in phosphate-buffered saline,plasma,and serum to simulate clinical situations.We determined the limit of detection as 1 ng/ml,and a good linear relationship was established between PCT concentration and color intensity within the detection range 1–10 ng/ml.Importantly,only a relatively short detection time(40 min)was required in all three environments.The results demonstrate the great potential of this device for biomarker detection and facilitating biomedical research.
基金supported by the AMS Funding Project(No.ZZB2023C7010).
文摘Glial fibrillary acidic protein(GFAP)is one of the discriminative biomarkers for diagnosing traumatic brain injury(TBI),and accurate determination of GFAP is clinically significant.In this study,a novel fluorescence immunoassay system was designed.We encapsulated carbon dots with a high fluorescence quantum yield(QY=92.5%)inside silicon nanocapsules to serve as fluorescent markers.These markers were then integrated with the streptavidin(SA)-biotin biomagnification system and immunomagnetic separation technology for the sensitive detection of GFAP.Based on the signal cascade amplification effect of the silicon nanocapsules and SA-biotin,the fluorescence signal of the SA-biotin-modified immunofluorescence nanocapsules increased 3.6-fold compared to the carbon dot-based immunoprobe.The fluorescence immunoassay system was constructed for GFAP using SA-biotin-modified immunocapsules as the sensing probe and immunomagnetic nanoparticles as the immunorecognition probe.The fluorescence immunoassay system can specifically and ultra-sensitively quantify GFAP in blood samples,with a detection range of 10 pg/mL–10 ng/mL and detection limits of 3.2 pg/mL(serum)and 3.6 pg/mL(plasma).Moreover,the fluorescence immunoassay system exhibited prominent recoveries of 99.4%–100.4%(phosphate buffered saline),96%–102.6%(serum),and 93.2%–110.2%(plasma),with favorable specificity and excellent stabilization.The novel fluorescence immunoassay system provides a new approach to the clinical analysis of GFAP and may serve as a potential tool for screening and diagnosing TBI.
基金Financial supports from the National Natural Science Foundation of China(NSFC,Nos.52272144 and 22205048)Heilongjiang Provincial Natural Science Foundation of China(No.JQ2022E001)+3 种基金China Postdoctoral Science Foundation(Nos.2022M710931 and 2023T160154)Heilongjiang Postdoctoral Science Foundation(No.LBH-Z22010)Natural Science Foundation of Shandong Province(No.ZR2020ZD42)the Fundamental Research funds for the Central Universities are greatly acknowledged.
文摘Lateral flow immunoassay(LFIA),a rapid detection technique noted for simplicity and economy,has showcased indispensable applicability in diverse domains such as disease screening,food safety,and environmental monitoring.Nevertheless,challenges still exist in detecting ultra-low concentration analytes due to the inherent sensitivity limitations of LFIA.Recently,significant advances have been achieved by integrating enzyme activity probes and transforming LFIA into a highly sensitive tool for rapidly detecting trace analyte concentrations.Specifically,modifying natural enzymes or engineered nanozymes allows them to function as immune probes,directly catalyzing the production of signal molecules or indirectly initiating enzyme activity.Therefore,the signal intensity and detection sensitivity of LFIA are markedly elevated.The present review undertakes a comprehensive examination of pertinent research literature,offering a systematic analysis of recently proposed enzyme-based signal amplification strategies.By way of comparative assessment,the merits and demerits of current approaches are delineated,along with the identification of research avenues that still need to be explored.It is anticipated that this critical overview will garner considerable attention within the biomedical and materials science communities,providing valuable direction and insight toward the advancement of high-performance LFIA technologies.
