Progress in Mechanical Modeling of Implantable Flexible Neural Probes

Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.

Recent advances in single fluorescent probes for monitoring dual organelles in two channels

Organelles are specialized areas where cells perform specific processes necessary for life and actively communicate with each other to keep the whole cell func-tioning.Disorders of the organelle networks are associated with multiple patho-logical processes.However,clearly and intuitively visualizing the highly dynamic interactions between ultrafine organelles is challenging.Fluorescence imaging technology provides opportunities due to the distinct advantages of facile,non-invasiveness and dynamic detection,making it particularly well-suited for appli-cations in uncovering the mysterious veil of organelle interactions.Regrettably,the lack of ideal fluorescence agents has always been an obstacle in imaging the intricate behaviors of organelles.In this review,we provide a systematic discussion on the existing dual-color and dual-targetable molecular sensors used in moni-toring organelle interactions,with a specific focus on their targeting strategies,imaging mechanisms and biological applications.Additionally,the current limi-tations and future development directions of dual-targetable probes and dual-emissives are briefly discussed.This review aims to provide guidance for re-searchers to develop more improved probes for studying organelle interactions in the biomedical field.

Recent advances in self-immobilizing fluorescent probes for in vivo imaging

In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions.However,the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.Notably,self-immobilizing fluorescent probes that selectively recognize diseased tissues while improving in situ retention and enrichment enable accurate high-fidelity fluorescence imaging.In this review,we aim to summarize the strategies employed for recent advances in the performance and precision of in vivo fluorescence imaging using self-immobilizing techniques.Lastly,we discuss the prospects and potential challenges associated with selfimmobilizing fluorescent probes to promote further development and application of more delicate fluorescent probes.

Lift-Off Effect of Koch and Circular Differential Pickup Eddy Current Probes

A flexible or planar eddy current probe with a differential structure can suppress the lift-off noise during the inspection of defects.However,the extent of the lift-off effect on differential probes,including different coil structures,varies.In this study,two planar eddy current probes with differential pickup structures and the same size,Koch and circular probes,were used to compare lift-off effects.The eddy current distributions of the probes perturbed by 0°and 90°cracks were obtained by finite element analysis.The analysis results show that the 90°crack can impede the eddy current induced by the Koch probe even further at relatively low lift-off distance.The peak-to-peak values of the signal output from the two probes were compared at different lift-off distances using finite element analysis and experimental methods.In addition,the effects of different frequencies on the lift-off were studied experimentally.The results show that the signal peak-to-peak value of the Koch probe for the inspection of cracks in 90°orientation is larger than that of the circular probe when the lift-off distance is smaller than 1.2 mm.In addition,the influence of the lift-off distance on the peak-to-peak signal value of the two probes was studied via normalization.This indicates that the influence becomes more evident with an increase in excitation frequency.This research discloses the lift-off effect of differential planar eddy current probes with different coil shapes and proves the detection merit of the Koch probe for 90°cracks at low lift-off distances.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Smart molecular probes with controllable photophysical property for smart medicine

Precision medicine calls for advanced theranostics that integrate controllable diagnostic and therapeutic capabilities into one platform for disease treatment in the early stage.Phototheranostics such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT)have attracted considerable attention in recent years,which mainly employ different excited-state energy dissipation pathways of a chromophore.According to the Jablonski diagram,FLI is related to the radiative process,PAI and PTT are derived from the nonradiative thermal deactivation,and PDT originates from the triplet state energy,in which these processes are usually competitive.Therefore,it is critically important to precisely tune the photophysical energy transformation processes to realize certain diagnosis and treatment properties in optimal state for boosting biomedical applications.Currently,there are mainly two strategies including chemical structure and aggregate behavior changes that relate to the regulation of excited state energy dissipation.In this review,we will discuss the recent advances of smart molecular probes that the photophysical properties can be regulated by external triggers and their applications in biomedical fields.We will summarize the development of activatable phototheranostic molecular probes in response to stimuli such as reactive oxygen species,pH,light,hypoxia,enzyme and gas.The assembly and disassembly of molecular aggregates that greatly affect the photophysical energy transformation processes will also be highlighted.This review aims to provide valuable insights into the development of more accurate diagnostic and therapeutic systems,thereby advancing the emerging field of smart medicine.

Fluorescent probes for imaging and detection of plant hormones and their receptors

Exploring plant behavior at the cellular scale in a minimally invasive manner is critical to understanding plant adaptation to the environment.Phytohormones play vital regulatory roles in multiple aspects of plant growth and development and acclimation to environmental changes.Since the biosynthesis,modification,transportation,and degradation of plant hormones in plants change with time and space,their content level and distribution are highly dynamic.To monitor the production,transport,perception,and distribution of phytohormones within undamaged tissues,we require qualitative and quantitative tools endowed with remarkably high temporal and spatial resolution.Fluorescent probes are regarded as excellent tools for widespread plant imaging because of their high sensitivity and selectivity,reproducibility,real-time in situ detection,and uncomplicated mechanism elucidation.In this review,we provide a systematical overview of the progress in the sensing and imaging of phytohormone fluorescent probes and fluorescently labeled phytohormones to their receptors in plants.Moreover,forthcoming viewpoints and possible applications of these fluorescent probes within the realm of plants are also presented.We hold the conviction that the new perspective brought by this paper can promote the development of fluorescent probes,enabling them to have better detection performance in plant hormone imaging.

Recent advances in dual response molecular probes for biothiols

The detection of biothiols such as cysteine(Cys),homocysteine(Hcy),and glutathione(GSH)are critical for understanding their roles in biology and their involvement in various physiological and pathological processes.Recently,significant progress has been made in constructing fluorescent probes capable of detecting and visualizing biothiols.This review provides an in-depth look at the latest advancements in simultaneous and selective molecular probes,focusing on developments over the last 5 years.We examine design techniques,sensing mechanisms,and imaging methods to assess their effectiveness and responsiveness to thiols.Additionally,we discuss the prevailing challenges and offer recommendations to address them.

Application of restriction display PCR technique in the preparation of cDNA microarray probes

AIM: To develop a simplified and efficient method for the preparation of hepatitis C virus (HCV) cDNA microarray probes.METHODS: With the technique of restriction display PCR (RD-PCR), restriction enzyme Sau3A I was chosen to digest the full-length HCV cDNAs. The products were classified and re-amplified by RD-PCR. We separated the differential genes by polyacrylamide gel electrophoresis and silver staining. Single bands cut out from the polyacrylamide gel were isolated. The third-round PCR was performed using the single bands as PCR template.The RD-PCR fragments were purified and cloned into the pMD18-T vector. The recombinant plasmids were extracted from positive clones, and the target gene fragments were sequenced. The cDNA microarray was prepared by spotting RD-PCR products to the surface of amino-modified glass slides using a robot. We validated the detection of microarray by hybridization and sequence analysis.RESULTS: A total of 24 different cDNA fragments ranging from 200 to 800 bp were isolated and sequenced,which were the specific gene fragments of HCV. These fragments could be further used as probes in microarray preparation. The diagnostic capability of the microarray was evaluated after the washing and scanning steps. The results of hybridization and sequence analysis showed that the specificity, sensitivity, accuracy, reproducibility,and linearity in detecting HCV RNA were satisfactory.CONCLUSION: The RD-PCR technique is of great value in obtaining a large number of size-comparable gene probes, which provides a speedy protocol in generating probes for the preparation of microarrays. Microarray prepared as such could be further optimized and applied in the clinical diagnosis of HCV.

Development of oligonucleotide probes for FISH karyotyping in Haynaldia villosa,a wild relative of common wheat

Haynaldia villosa is a wild relative of wheat and a valuable gene resource for wheat improvement.Owing to the limited number of probes available for fluorescence in situ hybridization(FISH),the resolution at which the karyotype of H.villosa can be characterized is poor,hampering accurate characterization of small segmental alien introgressions.We designed ten oligonucleotide probes using tandem repeats in DNA sequences derived from the short arm of H.villosa chromosome 6 V(6 VS).FISH with seven of them resulted in clear signals on H.villosa chromosomes.Using these,we constructed FISH karyotypes for H.villosa using oligo-6 VS-1 and oligo-6 VS-35 oligonucleotides and characterized the distribution of the two probes in five different H.villosa accessions.The new FISH probes can efficiently characterize H.villosa introgressions into wheat.

Hydroxylated graphene quantum dots as fluorescent probes for sensitive detection of metal ions

Highly sensitive methods are important for monitoring the concentration of metal ions in industrial wastewater.Here,we developed a new probe for the determination of metal ions by fluorescence quenching.The probe consists of hydroxylated graphene quantum dots(H-GQDs),prepared from GQDs by electrochemical method followed by surface hydroxylation.It is a non-reactive indicator with high sensitivity and detection limits of 0.01μM for Cu2+,0.005μM for Al3+,0.04μM for Fe3+,and 0.02μM for Cr3+.In addition,the low biotoxicity and excellent solubility of H-GQDs make them promising for application in wastewater metal ion detection.

An empirical model of the global distribution of plasmaspheric hiss based on Van Allen Probes EMFISIS measurements

Using wave measurements from the EMFISIS instrument onboard Van Allen Probes,we investigate statistically the spatial distributions of the intensity of plasmaspheric hiss waves.To reproduce these empirical results,we establish a fitting model that is a thirdorder polynomial function of L-shell,magnetic local time(MLT),magnetic latitude(MLAT),and AE*.Quantitative comparisons indicate that the model’s fitting functions can reflect favorably the major empirical features of the global distribution of hiss wave intensity,including substorm dependence and the MLT asymmetry.Our results therefore provide a useful analytic model that can be readily employed in future simulations of global radiation belt electron dynamics under the impact of plasmaspheric hiss waves in geospace.

Diagnosis of Hydrogen Plasma in a Miniature Penning Ion Source by Double Probes

Parameters of hydrogen plasma in a miniature Penning discharge ion source, including the electron temperature and the electron density, were measured by using double probes. The results indicate that the electron density increases and the electron temperature decreases with the increase in gas pressure and the discharge current. The electron temperature is about 5 - 9 eV and the electron density is 6.0× 10^13 ～ 1.2 × 10^14 m^-3 while the discharge current is in a range of 50 - 120 μA.

Ultrasensitive Detection of Glyphosate Using CdTe Quantum Dots in Sol-Gel-Derived Silica Spheres Coated with Calix[6]arene as Fluorescent Probes

We have developed a simple method for the preparation of highly fluorescent and stable, water-soluble CdTe quantum dots in sol-gel-derived composite silica spheres which were coated with calix[6]arene. The resulting nanoparticles (NPs) were characterized in terms of UV, fluorescence and FT-IR spectroscopy and TEM. The results show that the new NPs display more intense fluorescence intensity and are more stable than its precursors of the type SiO2/CdTe. Under the optimum, the novel NPs exhibit a higher selectivity and ultrasensitive fluorescence probes for the determination of gly-phosate over other pesticides, the fluorescence intensity increase with the concentration of glyphosate in the range from 1.0 to 25.0 nmol/L and the detection limit is low to 0.0725 nmol/L. A mechanism is suggested to explain the inclusion process by a Langmuir binding isotherm.

Application and development of fluorescence probes in MINFLUX nanoscopy(invited paper)

The MINimal emission FLUXes(MINFLUX)technique in optical microscopy,widely recognized as the next innovative fluorescence microscopy method,claims a spatial resolution of 1-3 nm in both dead and living cells.To make use of the full resolution of the MINFLUX microscope,it is important to select appropriate fluorescence probes and labeling strategies,especially in living-cell imaging.This paper mainly focuses on recent applications and developments of fluorescence probes and the relevant labeling strategy for MINFLUX microscopy.Moreover,we discuss the deficiencies that need to be addressed in the future and a plan for the possible progression of MINFLUX to help investigators who have been involved in or are just starting in the field of super-resolution imaging microscopy with theoretical support.

ACTIVATABLE SMART PROBES FOR MOLECULAR OPTICAL IMAGING AND THERAPY

Recent years have seen the design and implementation of many optical activatable smart probes.These probes are activatable because they change their optical properties and are smart because they can identify specific targets.This broad class of detection agents has allowed previously unperformed visualizations,facilitating the study of diverse biomolecules including enzymes,nucleic acids,ions and reactive oxygen species.Designed to be robust in an in vivo environment,these probes have been used in tissue culture cells and in live small animals.An emerging class of smart probes has been designed to harness the potency of singlet oxygen generating photosensitizers.Combining the discrimination of activatable agents with the toxicity of photosensitizers represents a new and powerful approach to disease treatment.This review highlights some applications of activatable smart probes with a focus on developments of the past decade.

Study on mutual impedance characteristics between probes in a circular waveguide

The expression of mutual impedance between two probes in a circular waveguide is derived by means of a vector potential function, reaction concept and reciprocity theorem. The waveguide is semi-infinite, and one end of the waveguide is terminated to a load with a reflection coefficient. The contribution to the mutual resistance is found to come from the dominant mode, while the contribution to the mutual reactance comes from the dominant mode and the higher order modes. The major contribution to the mutual reactance is from the dominant mode, since the higher modes decay rapidly with the increasing the probes’ of separation distance. However, as the separation distance approaches zero, the higher modes become dominant, which results in a large value of the mutual reactance. The mutual impedance is dependent on the location and height of the probes, their separation distance and the location of the terminal plane.

Recent development of organic small-molecule and nanomaterial fluorescent probes for hydrazine

Hydrazine,an essential chemical,has been used within a wide spectrum of industries,including pesticides,pharmaceuticals and even satellite-launching systems.However,the excessive consumption of hydrazine raised the risk of environmental pollution accidents and occurrence of diseases because of its high toxicity and volatility.This led to the discovery of diverse fluorescent probes for the monitoring of the dangerous substance,including those based on organic small molecules and emerging nanomaterials.Herein,we are going to present a comprehensive review of recently reported hydrazine fluorescent probes,and discuss their structure design strategies and detection mechanisms.In particular,both organic small-molecule and nanomaterial fluorescent probes for hydrazine will be discussed together for the first time.

Synthesis of Photoactivatable Phospholipidic Probes

We synthesized and characterized photoactivatable phospholipidic probes 1-3. These probes have the perfluorinated aryl azide function at the polar head of phospholipid. They are stable in dark and become highly reactive upon photoirradiation. The preliminary results suggest that they are promising tools to study the topology of membrane proteins and protein-lipid interactions using photolabeling approach.

Detection of HBV and HCV Coinfection by TEM with Au Nanoparticle Gene Probes

Gold（Au） nanoparticle HBV DNA or HCV cDNA gene probes were prepared and were used to detect HBV DNA and HCV RNA extracted from positive serum of patients with HBV and HCV coinfection directly by transmission electron microscopy （TEM）. PCR identifying HBV and HCV in serum of patients with HBV and HCV coinfection was established. Alkanethiol-modified oligonucleotide was bound with self-made Au nanoparticles to form nanoparticle HBV DNA or HCV cDNA gene probes through covalent binding of Au-S. HBV DNA and HCV RNA extracted from positive serum of patients with HBV and HCV coinfection was added to the detection system composed of nanoparticle HBV DNA and（or） HCV cDNA gene probes, The results showed that HBV DNA and HCV RNA could be specifically amplified by PCR. The zones of DNA amplification appeared in 431 bp and 323 bp respectively. When HBV DNA and HCV RNA extracted from positive serum of patients with HBV and HCV coinfection were added to the detection system, TEM displayed the nanoparticles self-assembled into large network aggregates. It was concluded that the detection of HBV and HCV coinfection by TEM was convenient and efficient with high specificity and sensitivity.