Recent Progress in Endoplasmic Reticulum-Targetable Small-Molecule Probes for Fluorescence Sensing and Phototherapy

The endoplasmic reticulum(ER)is the most widespread organelle within eukaryotic cells,performing various essential functions such as protein synthesis,post-translational modifications,and lipid metabolism.Abnormal fluctuations of biologically active species and microenvironments in the ER can disrupt homeostasis and eventually lead to ER stress,which is closely linked to the occurrence and progression of many human diseases.Therefore,the ER has been regarded as an important analytical object as well as a promising therapeutic target in both bio sensing and biomedicine.Recently,there has been a growing interest in developing photon-excited molecular tools to uncover the physio pathological roles of ER and treat ERrelated disorders.This review presents a comprehensive summary of recent advances in ER-targeted small-molecule probes and their applications for fluorescent sensing and phototherapy,mainly focusing on targeting strategies and probe design principles.Last,we discuss the challenges involved with ER-targeted probes and highlight potential prospects in this field.

An exo Probe-based Reverse Transcription and Recombinase Polymerase Amplification for Rapid Detection of Feline Calicivirus in Cats

Feline calicivirus(FCV)was a highly prevalent RNA virus causing upper respiratory tract infections in cats through the mouth and nose around the world,result in the death of cats especially under 1 year old with upper respiratory tract disease(URTD)and virulent systemic disease(FCV-VSD)[1].Infected cats usually presented with mouth ulcers,salivation and gingivitis-stomatitis.Furthermore,both recovered cats and asymptomatic carriers can still carry and spread the FCV virus for extended periods of time,contributing to the potential for outbreak.This presented a significant threat to the health and lives of cats,and rare wildlife and took a heavy financial loss on the pet industry,making the prevention and control of the virus difficult.Hence,rapid identification of FCV in clinical samples was necessary to prevent the spread of FCV and avoid financial loss.

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.

Plasma potential measurements using an emissive probe made of oxide cathode

A novel emissive probe consisting of an oxide cathode coating is developed to achieve a low operating temperature and long service life.The properties of the novel emissive probe are investigated in detail,in comparison with a traditional tungsten emissive probe,including the operating temperature,the electron emission capability and the plasma potential measurement.Studies of the operating temperature and electron emission capability show that the tungsten emissive probe usually works at a temperature of 1800 K-2200 K while the oxide cathode emissive probe can function at about 1200 K-1400 K.In addition,plasma potential measurements using the oxide cathode emissive probe with different techniques have been accomplished in microwave electron cyclotron resonance plasmas with different discharge powers.It is found that a reliable plasma potential can be obtained using the improved inflection point method and the hot probe with zero emission limit method,while the floating point method is invalid for the oxide cathode emissive probe.

Design of compact integrated diamond nitrogen-vacancy center quantum probe

An integrated quantum probe for magnetic field imaging is proposed,where the nitrogen–vacancy(NV)center fixed at the fiber tip is located on the periphery of flexible ring resonator.Using flexible polyimide(PI)as the substrate medium,we design a circular microstrip antenna,which can achieve a bandwidth of 140 MHz at Zeeman splitting frequency of 2.87 GHz,specifically suitable for NV center experiments.Subsequently,this antenna is seamlessly fixed at a three-dimensional-printed cylindrical support,allowing the optical fiber tip to extend out of a dedicated aperture.To mitigate errors originating from processing,precise tuning within a narrow range can be achieved by adjusting the conformal amplitude.Finally,we image the microwave magnetic field around the integrated probe with high resolution,and determine the suitable area for placing the fiber tip(SAP).

Distal-scanning common path probe for optical coherence tomography

In this paper,we present a distal-scanning common path probe for optical coherence tomography(OCT)equipped with a hollow ultrasonic motor and a simple and specially designed beam-splitter.This novel probe proves to be able to effectively circumvent polarization and dispersion mismatch caused by fiber motion and is more robust to a variety of interfering factors during the imaging process,experimentally compared to a conventional noncommon path probe.Furthermore,our design counteracts the attenuation of backscattering with depth and the fall-off of the signal,resulting in a more balanced signal range and greater imaging depth.Spectral-domain OCT imaging of phantom and biological tissue is also demonstrated with a sensitivity of∼100dB and a lateral resolution of∼3μm.This low-cost probe offers simplified system configuration and excellent robustness,and is therefore particularly suitable for clinical diagnosis as one-off medical apparatus.

Temperature-controlled DCP Fluorescent Probe Based on Hydrogel-immobilized Quantum Dots Composite

A composite was created by incorporating the quantum dot-enhanced SiO_(2)nanoparticles within this hydrogel.Based on this composite,a temperature-controlled fluorescent probe for DCP was developed.A meticulous examination of this probe revealed its attributes and factors affecting its performance.By using temperature modulation,the probe was adept at detecting DCP concentrations ranging between 1.0×10^(-6)and 9.0×10^(-6)mol/L.Such a probe offers remarkable selectivity,repeatability,and robust stability,so that the detection of DCP can be carried out at different temperatures,and a fast,reliable,sensitive and low-cost intelligent detection method is realized.

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.

Tb^(3+)-nucleic acid probe-based label-free and rapid detection of mercury pollution in food

Mercury is a threatening pollutant in food,herein,we developed a Tb^(3+)-nucleic acid probe-based label-free assay for mix-and-read,rapid detection of mercury pollution.The assay utilized the feature of light-up fluorescence of terbium ions(Tb^(3+))via binding with single-strand DNA.Mercury ion,Hg^(2+)induced thymine(T)-rich DNA strand to form a double-strand structure(T-Hg^(2+)-T),thus leading to fluorescence reduction.Based on the principle,Hg^(2+)can be quantified based on the fluorescence of Tb^(3+),the limit of detection was 0.0689μmol/L and the linear range was 0.1-6.0μmol/L.Due to the specificity of T-Hg^(2+)-T artificial base pair,the assay could distinguish Hg^(2+)from other metal ions.The recovery rate was ranged in 98.71%-101.34%for detecting mercury pollution in three food samples.The assay is low-cost,separation-free and mix-to-read,thus was a competitive tool for detection of mercury pollution to ensure food safety.

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.

A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma

AIM:To directly quantify peroxynitrite(ONOO-)using a highly sensitive fluorescence resonance energy transfer probe RN-NA,investigate the association between ONOOand primary open angle glaucoma(POAG),and clarify whether RN-NA could be used as a potential tool for POAG diagnosis.METHODS:Plasma and aqueous humor(AH)samples were collected from POAG patients(n=100,age:59.70±6.87y)and age-related cataract(ARC)patients(n=100,age:61.15±4.60y)admitted to our hospital.Next,RN-NA was used to detect ONOO-in plasma and AH samples,and the relationship between ONOO-level and POAG was analyzed using binary logistic regression.Besides,Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO-with the patients’age,intraocular pressure(IOP),and mean deviation of visual field testing.The ONOO-scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine(SIN-1)-induced ocular hypertension in mice(n=7,6-8wk).Finally,the IOP and ONOO-in both eyes were measured 30min after the last drug treatment.RESULTS:ONOO-levels of AH and plasma were significantly higher in the POAG group than in the ARC group(P<0.01).Additionally,ONOO-levels were closely correlated with POAG in a binary logistic regression analysis[odds ratio(OR)=1.008,95%confidence interval(CI):1.002-1.013,P<0.01 for AH;OR=1.004,95%CI:1.002-1.006,P<0.001 for plasma].Pearson correlation analysis showed that ONOO-levels in AH or plasma were positively associated with visual field defects(R=0.51,P<0.01 for AH;R=0.45,P<0.001 for plasma),and ONOO-levels in plasma and AH were correlated in the POAG group(R=0.69,P<0.001).However,administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1(P<0.05).CONCLUSION:ONOO-levels in AH and plasma,detected by RN-NA,are significantly related to POAG and positively correlated with visual field defects in POAG patients.Hence,ONOO-is a potential biomarker of POAG,especially advanced POAG.Besides,anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

Study of plasma parameters of coaxial plasma source using triple Langmuir probe and Faraday cup diagnostics

Coaxial plasma guns are a type of plasma source that produces plasma which propagates radially and axially controlled by the shape of the ground electrode, which has attracted much interest in several applications. In this work, a 120° opening angle of CPG nozzle is used as a plasma gun configuration that operates at the energy of 150 J. The ionization of polyethylene insulator between the electrodes of the gun produces a cloud of hydrogen and carbon plasma.The triple Langmuir probe and Faraday cup are used to measure plasma density and plasma temperature. These methods are used to measure the on-axis and off-axis plasma divergence of the coaxial plasma gun. The peak values of ion densities measured at a distance of 25 mm on-axis from the plasma gun are(1.6±0.5)×10^(19)m^(-3)and(2.8±0.6)×10^(19)m^(-3)for hydrogen and carbon plasma respectively and the peak temperature is 3.02±0.5 eV. The mean propagation velocity of plasma is calculated using the transit times of plasma at different distances from the plasma gun and is found to be 4.54±0.25 cm/μs and 1.81±0.18 cm/μs for hydrogen and carbon plasma respectively. The Debye radius is obtained from the measured experimental data that satisfies the thin sheath approximation. The shot-to-shot stability of plasma parameters facilitates the use of plasma guns in laboratory experiments. These types of plasma sources can be used in many applications like plasma opening switches, plasma devices, and as plasma sources.

Scanning transmission electron microscopy and atom probe tomography analysis of non-stoichiometry long-period-stacking-ordered structures in Mg-Ni-Y/Sm alloys

The long-period-stacking-ordered(LPSO)structure affects the mechanical,corrosion and hydrolysis properties of Mg alloys.The current work employs high angle annular dark field-scanning transmission electron microscopy(HAADF-STEM)and atom probe tomography(APT)to investigate the structural and local chemical information of LPSO phases formed in Mg-Ni-Y/Sm ternary alloys after extended isothermal annealing.Depending on the alloying elements and their concentrations,Mg-Ni-Y/Sm develops a two-phase LPSO+α-Mg structure in which the LPSO phase contains defects,hybrid LPSO structure,and Mg insertions.HAADF-STEM and APT indicate non-stoichiometric LPSO with incomplete Ni_(6)(Y/Sm)_(8) clusters.In addition,the APT quantitatively determines the local composition of LPSO and confirms the presence of Ni within the Mg bonding layers.These results provide insight into a better understanding of the structure and hydrolysis properties of LPSO-Mg alloys.

Multinuclear MR and MRI study of lithium-ion cells using a variable field magnet and a fixed frequency RF probe

An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the study.The magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 MHz.Two cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were interrogated.One cell was pristine,and one was charged to a cell voltage of 4.2 V.The results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion batteries.These methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.

Functional lumen imaging probe use in a high-volume practice:Practical and technical implications

BACKGROUND The functional lumen imaging probe(FLIP)is a Food and Drug Administration approved tool to aid the diagnosis and management of esophageal disorders.However,widespread adoption of FLIP remains limited and its utility in highvolume practices remains unclear.AIM To analyze large sample data on clinical use of FLIP and provide insight on several technical aspects when performing FLIP.METHODS We conducted a retrospective comparative and descriptive analysis of FLIP procedures performed by a single provider at an academic medical center.There was a total of 398 FLIP procedures identified.Patient medical records were reviewed and data regarding demographics and procedural details were collected.Statistical tests,including chi-squared,t-test,and multivariable logistic and linear regression,were performed.RESULTS There was an increase in FLIP cases with each successive time period of 13 months(n=68,146,184,respectively)with notable rises specifically for indications of dysphagia and gastroesophageal reflux disease.There was a shift toward use of the longer FLIP balloon catheter for diagnostic purposes(overall 70.4%vs 29.6%,P<0.01).Many cases(42.8%)were performed in conjunction with other diagnostics/interventions,such as dilation and wireless pH probe placement.Procedures were nearly equally performed with anesthesia vs moderate sedation(51.4%anesthesia),with no major complications.Patients who had anesthesia were less likely to have recurrent antegrade contractions[odds ratio(OR)=0.4,95%CI:0.3-0.8]and were also more likely to have absent contractility(OR=2.4,95%CI:1.3-CONCLUSION FLIP cases have increased in our practice with expanding indications for its use.Given limited normative data,providers should be aware of several potential technical issues,including the possible impact of sedation choice when assessing esophageal motility patterns.

Controllable Synthesis of Au NRs and Its Flexible SERS Optical Fiber Probe with High Sensitivity

The surface-enhanced Raman scattering(SERS) optical fiber probes were successfully prepared by self-assembling on polyelectrolyte multilayers. Gold nanorods(Au NRs) were used as SERS enhancement material to give excellent biological affinity and stability to the SERS optical fiber probes. Au NRs were synthesized by seed growth method. The synergistic effect between AgNO_(3) and surfactant was investigated, and the highest yield was found when AgNO_(3) was 500 uL. Meanwhile, different SERS optical fiber probes were obtained by selecting silane coupling agent, polyelectrolyte multilayer and graphene oxide(GO) to treat quartz fiber. It was found that the SERS optical fiber probes obtained by the self-assembled on polyelectrolyte multilayers method performed better than those by other methods. In addition, Mapping was combined with finite element simulation to analyze the electromagnetic field distribution at the fiber end face.The electromagnetic field distribution of Au NRs was investigated, the difference of electromagnetic field intensity around the Au NRs with different arrangements was compared, the strongest signal was obtained when the Au NRs were head-to-head. Finally, sensitivity of the optimized SERS optical fiber probes could reach 10^(-9)mol/L, with excellent stability and repeatability.

A ratiometric fluorescent probe for hypoxanthine detection in aquatic products based on the enzyme mimics and fluorescence of cobalt-doped carbon nitride

A ratiometric fluorescent probe for hypoxanthine(Hx)detection was established based on the mimic enzyme and fluorescence characteristics of cobalt-doped graphite-phase carbon nitride(Co doped g-C_(3)N_(4)).In addition to emitting strong fluorescence,the peroxidase activity of Co doped g-C_(3)N_(4)can catalyze the reaction of O-phenylenediamine and H_(2)O_(2)to produce diallyl phthalate which can emit yellow fluorescence at 570 nm.Through the decomposition of Hx by xanthine oxidase,Hx can be indirectly detected by the generating hydrogen peroxide based on the measurement of fluorescent ratio I(F_(570)/F_(370)).The linear range was 1.7-272.2 mg/kg(R^(2)=0.997),and the detection limit was 1.52 mg/kg(3σ/K,n=9).The established method was applied to Hx detection in bass,grass carp,and shrimp,and the data were verified by HPLC.The result shows that the established probe is sensitive,accurate,and reliable,and can be used for Hx detection in aquatic products.

Correlation of work function and stacking fault energy through Kelvin probe force microscopy and nanohardness in diluteα-magnesium

Electronic interactions of the Group 2A elements with magnesium have been studied through the dilute solid solutions in binary Mg-Ca,Mg-Sr and Mg-Ba systems.This investigation incorporated the difference in the‘Work Function'(ΔWF)measured via Kelvin Probe Force Microscopy(KPFM),as a property directly affected by interatomic bond types,i.e.the electronic structure,nanoindentation measurements,and Stacking Fault Energy values reported in the literature.It was shown that the nano-hardness of the solid-solutionα-Mg phase changed in the order of Mg-Ca>Mg-Sr>Mg-Ba.Thus,it was shown,by also considering the nano-hardness levels,that SFE of a solid-solution is closely correlated with its‘Work Function'level.Nano-hardness measurements on the eutectics andΔWF difference between eutectic phases enabled an assessment of the relative bond strength and the pertinent electronic structures of the eutectics in the three alloys.Correlation withΔWF and at least qualitative verification of those computed SFE values with some experimental measurement techniques were considered important as those computational methods are based on zero Kelvin degree,relatively simple atomic models and a number of assumptions.As asserted by this investigation,if the results of measurement techniques can be qualitatively correlated with those of the computational methods,it can be possible to evaluate the electronic structures in alloys,starting from binary systems,going to ternary and then multi-elemental systems.Our investigation has shown that such a qualitative correlation is possible.After all,the SFE values are not treated as absolute values but rather become essential in comparative investigations when assessing the influences of alloying elements at a fundamental level,that is,free electron density distributions.Our study indicated that the principles of‘electronic metallurgy'in developing multi-elemental alloy systems can be followed via practical experimental methods,i.e.ΔWF measurements using KPFM and nanoindentation.

“Einstein Probe”Mission Holds New Promise in Time-domain Astronomy

Einstein Probe,an astronomical satellite designed for X-ray observation on astronomical events drastically evolving over time,was successfully sent into preset orbit by a Long March 2C rocket from China’s Xichang Satellite Launch Center located in Sichuan Province at 15:03 GMT+8 on January 9,2024.