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.

3,6-Bis-β-Dicarbonylsubstituted Carbazoles Bearing N-Spacers and Their Eu(III) Complexes as Immunofluorescent Labelling Agents

New reagents for immunofluorescence analysis of carbazole series containing fluorinated β-dicarbonyl fragments and carboxylic substituent groups separated by spacers of different lengths from the light-gathering carbazole scaffold have been developed. The markers in complex with Eu3+ ions possess stability in the aqueous phase, intense and prolonged luminescence (τ 550 - 570 μs) with characteristic emission maxima in the region of 615 nm and excitation wavelengths in the region of 380 - 390 nm, which distinguishes them from most of the analogs used. In the study of marker conjugation with streptavidin, a reagent containing 4 - 5 europium labeling complexes based on spacer-containing carbazole tetraketone was obtained. The marker-doped silicate nanoparticles exhibit intense and long-lived luminescence in the characteristic region.

Fluorescent Double Network Hydrogels with Ionic Responsiveness and High Mechanical Properties for Visual Detection

We developed a fluorescent double network hydrogel with ionic responsiveness and high mechanical properties for visual detection.The nanocomposite hydrogel of laponite and polyacrylamide serves as the first network,while the ionic cross-linked hydrogel of terbium ions and sodium alginate serves as the second network.The double-network structure,the introduction of nanoparticles and the reversible ionic crosslinked interactions confer high mechanical properties to the hydrogel.Terbium ions are not only used as the ionic cross-linked points,but also used as green emitters to endow hydrogels with fluorescent properties.On the basis of the “antenna effect” of terbium ions and the ion exchange interaction,the fluorescence of the hydrogels can make selective responses to various ions(such as organic acid radical ions,transition metal ions) in aqueous solutions,which enables a convenient strategy for visual detection toward ions.Consequently,the fluorescent double network hydrogel fabricated in this study is promising for use in the field of visual sensor detection.

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.

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.

L-shell x-ray fluorescence relative intensities for elements with 62≤Z≤83 at 18 keV and 23 keV by synchrotron radiation

The relative intensities of L-subshell x-ray fluorescence(XRF)for elements with atomic numbers 62≤Z≤83 were measured at two excitation energies,18 keV and 23 keV,using a synchrotron radiation source at a beamline of the Synchrotron Light Center for Experimental Science and Applications in the Middle East(SESAME),Jordan.The experimentally measured results of the relative intensities were compared with the calculated results using the subshell fluorescence yield and the Coster-Kronig transition probabilities recommended by Campbell and the values based on the Dirac-Hartree-Slater model by Puri.The experimental and theoretical results are in agreement.In this work,L XRF relative intensities for the elements Sm,Gd,Tb,Er,Ta,W,Re,Hg,Pb and Bi at energies of 18 keV and 23 keV were measured.

Glancing incidence x-ray fluorescence spectrometry based on a single-bounce parabolic capillary

Glancing incidence x-ray fluorescence spectrometry using a single-bounce parabolic capillary is proposed for the analysis of layered samples.The divergence of the x-ray beam was 0.33 mrad.In this paper,we used this instrumental setup to analyze a Si single crystal and a 50 nm HfO_(2) single-layer film deposited on a Si substrate.

Elemental composition x-ray fluorescence analysis with a TES-based high-resolution x-ray spectrometer

The accurate analysis of the elemental composition plays a crucial role in the research of functional materials.The emitting characteristic x-ray fluorescence(XRF)photons can be used for precisely discriminating the specified element.The detection accuracy of conventional XRF methodology using semiconductor detector is limited by the energy resolution,thus posing a challenge in accurately scaling the actual energy of each XRF photon.We adopt a novel high-resolution x-ray spectrometer based on the superconducting transition-edge sensor(TES)for the XRF spectroscopy measurement of different elements.Properties including high energy resolution,high detection efficiency and precise linearity of the new spectrometer will bring significant benefits in analyzing elemental composition via XRF.In this paper,we study the Ledge emission line profiles of three adjacent rare earth elements with the evenly mixed sample of their oxide components:terbium,dysprosium and holmium.Two orders of magnitude better energy resolution are obtained compared to a commercial silicon drift detector.With this TES-based spectrometer,the spectral lines overlapped or interfered by background can be clearly distinguished,thus making the chemical component analysis more accurate and quantitative.A database of coefficient values for the line strength of the spectrum can then be constructed thereafter.Equipped with the novel XRF spectrometer and an established coefficient database,a direct analysis of the composition proportion of a certain element in an unknown sample can be achieved with high accuracy.

Carbon Nitride Quantum Dots:A Novel Fluorescent Probe for Non-Enzymatic Hydrogen Peroxide and Mercury Detection

The mercury species in the ocean(MeHg,Hg^(2+))will be enriched in marine organisms and threaten human health through the food chain.While the excessive H_(2)O_(2)in the metabolic process will produce hydroxyl radicals and accelerate the aging of human cells,causing a series of diseases.Hence,the cost-effective and rapid detection of mercury and H_(2)O_(2)is of urgent requirement and significance.Here,we synthesized emerging graphitic carbon nitride quantum dots(g-CNQDs)with high fluorescence quantum yield(FLQY)of 42.69%via a bottom-up strategy by a facile one-step hydrothermal method.The g-CNQDs can detect the H_(2)O_(2)and Hg^(2+)through the fluorescence quenching effect between g-CNQDs and detected substances.With the presence of KI,g-CNQDs show concentration-dependent fluorescence toward H_(2)O_(2),with a wide detection range of 1–1000μmolL^(-1)and a low detection limit of 0.23μmolL^(-1).The g-CNQDs also show sensitivity toward Hg^(2+)with a detection range of 0–0.1μmolL^(-1)and a detection limit of 0.038μmolL^(-1).This dual-function detection of g-CNQDs has better practical application capability compared to other quantum dot detection.This study may provide a new strategy for g-CNQDs preparation and construct a fluorescence probe that can be used in various systems involving H_(2)O_(2)and Hg^(2+),providing better support for future bifunctional or multifunction studies.

Accuracy analysis of iron content of galvanized coating using an X-ray fluorescence spectrometer with an L-spectrum

The accuracy(repeatability and reproducibility) of the iron content analysis of galvanized coating using an X-ray fluorescence spectrometer with an L-spectrum is not better than that of flame atomic absorption spectrometry, sometimes it exceeds the quality control limit.Influences, such as current, voltage, equipment(internal circulating water, 10%CH4+90%Ar, and vacuum) checking, instrument monitoring, sample cleaning, and oper-ators, were investigated by means of 6-sigma and lean operations to improve accuracy.

Comparison of the emission wavelengths by a single fluorescent dye on in vivo 3-photon imaging of mouse brains

Multiphoton microscopy(MPM)is a powerful imaging technology for brain research.The imaging depth in MPM is partly determined by emission wavelength of fluorescent labels.It has been demonstrated that a longer emission wavelength is favorable for signal detection as imaging depth increases.However,there has been no comparison with near-infrared(NIR)emission.In order to quantitatively analyze the effect of emission wavelength on 3-photon imaging of mouse brains in vivo,we utilize the same excitation wavelength to excite a single fluorescent dye and simultaneously collect NIR and orange-red emission fluorescence at 828 nm and 620 nm,respectively.Both experimental and simulation results show that as the imaging depth increases,NIR emission decays less than orange-red fluorescent emission.These results show that it is preferable to shift the emission wavelength to NIR to enable more e±cient signal collection deep in the brain.

Endoscopic fluorescent lymphography for gastric cancer

Lymphography by radioisotope or dye is a well-known technique for visualizing the lymphatic drainage pattern in a neoplastic lesion and it is in use in gastric cancer.Indocyanine green(ICG)more recently has been validated in fluorescent lymphography studies and is under evaluation as a novel tracer agent in gastric cancer.The amount and dilution of ICG injected as well as the site and the time of the injection are not standardized.In our unit,endoscopic submucosal injections of ICG are made as 0.5 mg in 0.5 mL at four peritumoral sites the day before surgery(for a total of 2.0 mg in 2.0 mL).Detection instruments for ICG fluorescence are evolving.Near-infrared systems integrated into laparoscopic or robotic instruments(near-infrared fluorescence imaging)have shown the most promising results.ICG fluorescence recognizes the node that receives lymphatic flow directly from a primary tumor.This is defined as the sentinel lymph node,and it has a high predictive negative value at the cT1 stage,able to reduce the extent of gastrectomy and lymph node dissection.ICG also enhances the number of lymph nodes detected during extended lymphadenectomy for advanced gastric cancer.Nevertheless,the practical effects of ICG use in a single patient are not yet clear.Standardization of the technique and further studies are needed before fluorescent lymphography can be used extensively worldwide.Until then,current guidelines recommend an extensive lymphadenectomy as the standard approach for gastric cancer with suspected metastasis.

X-ray在鱼体组织及微量元素检测中的应用

鱼类硬质组织物,特别是骨骼支持鱼体和保护其体内器官的组织,对其进行特征检测分析是研究鱼类游泳运动、鱼类解剖、鱼体建模等的数据基础。随着X-ray技术的发展和国产设备的广泛应用,其仪器设备成本明显降低,使得X-ray在渔业研究与自动化生产中的应用成为可能。首先介绍了X-ray技术的基本原理与其在鱼体组织检测中的应用,X-ray技术在鱼体组织及微量元素检测中的应用主要分为鱼类组织器官的无损检测和鱼体微量元素检测两部分,其中分别介绍了包括照相法、数字成像法、衍射技术和吸收光谱法等X-ray技术;然后综述其在鱼体组织器官建模、鱼骨检测、鱼类化石研究、鱼耳石分析和鱼体微量元素检测方面的应用,总结了Xray在渔业领域应用中存在的问题;最后对X-ray的渔业应用方向进行展望。

Preoperative 3D reconstruction and fluorescent indocyanine green for laparoscopic duodenum preserving pancreatic head resection:A case report

BACKGROUND Duodenum-preserving pancreatic head resection(DPPHR)is the choice of surgery for benign or low-grade malignant tumors of the pancreatic head.Laparoscopic DPPHR(LDPPHR)procedure can be improved by preoperative 3D model reconstruction and the use of intravenous indocyanine green fluorescent before surgery for real-time navigation with fluorescent display to guide the surgical dissection and prevention of from injury to vessels and biliary tract.CASE SUMMARY Here we report the successful short-and long-term outcomes after one year following LDPPHR for a 60-year lady who had an uneventful recovery and was discharged home one week after the surgery.CONCLUSION There was no bile leakage or pancreatic leakage or delayed gastric emptying.The histopathology report showed multiple cysts in the pancreatic head and localized pancreatic intraepithelial tumor lesions.The resected margin was free of tumor.

The Soft X-ray Imager(SXI)on the SMILE Mission

The Soft X-ray Imager(SXI)is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.SMILE is a joint science mission between the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)and is due for launch in 2025.SXI is a compact X-ray telescope with a wide field-of-view(FOV)capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit.SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange(SWCX)process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere.SWCX provides a mechanism for boundary detection within the magnetosphere,such as the position of Earth’s magnetopause,because the solar wind heavy ions have a very low density in regions of closed magnetic field lines.The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours.SXI is led by the University of Leicester in the United Kingdom(UK)with collaborating organisations on hardware,software and science support within the UK,Europe,China and the United States.

Global hybrid simulations of soft X-ray emissions in the Earth’s magnetosheath

Earth’s magnetopause is a thin boundary separating the shocked solar wind plasma from the magnetospheric plasmas,and it is also the boundary of the solar wind energy transport to the magnetosphere.Soft X-ray imaging allows investigation of the large-scale magnetopause by providing a two-dimensional(2-D)global view from a satellite.By performing 3-D global hybrid-particle-in-cell(hybrid-PIC)simulations,we obtain soft X-ray images of Earth’s magnetopause under different solar wind conditions,such as different plasma densities and directions of the southward interplanetary magnetic field.In all cases,magnetic reconnection occurs at low latitude magnetopause.The soft X-ray images observed by a hypothetical satellite are shown,with all of the following identified:the boundary of the magnetopause,the cusps,and the magnetosheath.Local X-ray emissivity in the magnetosheath is characterized by large amplitude fluctuations(up to 160%);however,the maximum line-of-sight-integrated X-ray intensity matches the tangent directions of the magnetopause well,indicating that these fluctuations have limited impact on identifying the magnetopause boundary in the X-ray images.Moreover,the magnetopause boundary can be identified using multiple viewing geometries.We also find that solar wind conditions have little effect on the magnetopause identification.The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will provide X-ray images of the magnetopause for the first time,and our global hybrid-PIC simulation results can help better understand the 2-D X-ray images of the magnetopause from a 3-D perspective,with particle kinetic effects considered.

Finding the magnetopause location using soft X-ray observations and a statistical inverse method

Variability in the location and shape of the dayside magnetopause is attributed to magnetic reconnection,a fundamental process that enables the transfer of mass,energy,and momentum from the solar wind into the magnetosphere.The spatial and temporal properties of the magnetopause,under varying solar and magnetospheric conditions,remain largely unknown because empirical studies using in-situ observations are challenging to interpret.Global wide field-of-view(FOV)imaging is the only means to simultaneously observe the spatial distribution of the plasma properties over the vast dayside magnetospheric region and,subsequently,quantify the energy transport from the interplanetary medium into the terrestrial magnetosphere.Two upcoming missions,ESA/CAS SMILE and NASA’s LEXI will provide wide-field imagery of the dayside magnetosheath in soft X-rays,an emission generated by charge exchange interactions between high charge-state heavy ions of solar wind origin and exospheric neutral atoms.High-cadence two-dimensional observations of the magnetosheath will allow the estimation of dynamic properties of its inner boundary,the magnetopause,and enable studies of its response to changes in the solar wind dynamic pressure and interplanetary magnetic field orientation.This work introduces a statistically-based estimation approach based on inverse theory to estimate the spatial distribution of magnetosheath soft X-ray emissivities and,with this,identify the location of the magnetopause over the Sun−Earth line.To do so,we simulate the magnetosheath structure using the MHD-based OpenGGCM model and generate synthetic soft X-ray images using LEXI’s orbit and attitude information.Our results show that 3-D estimations using the described statistically-based technique are robust against Poisson-distributed shot noise inherent to soft X-ray images.Also,our proposed methodology shows that the accuracy of both three-dimensional(3-D)estimation and the magnetopause standoff distance calculation highly depends on the observational point.

Two methods for separating the magnetospheric solar wind charge exchange soft X-ray emission from the diffuse X-ray background

Solar wind charge exchange(SWCX)is the process of solar wind high-valence ions exchanging charges with neutral components and generating soft X-rays.Recently,detecting the SWCX emission from the magnetosphere is proposed as a new technique to study the magnetosphere using panoramic soft X-ray imaging.To better prepare for the data analysis of upcoming magnetospheric soft X-ray imaging missions,this paper compares the magnetospheric SWCX emission obtained by two methods in an XMM-Newton observation,during which the solar wind changed dramatically.The two methods differ in the data used to fit the diffuse X-ray background(DXB)parameters in spectral analysis.The method adding data from the ROSAT All-Sky Survey(RASS)is called the RASS method.The method using the quiet observation data is called the Quiet method,where quiet observations usually refer to observations made by the same satellite with the same target but under weaker solar wind conditions.Results show that the spectral compositions of magnetospheric SWCX emission obtained by the two methods are very similar,and the changes in intensity over time are highly consistent,although the intensity obtained by the RASS method is about 2.68±0.56 keV cm^(-2)s^(-1)sr^(-1)higher than that obtained by the Quiet method.Since the DXB intensity obtained by the RASS method is about 2.84±0.74 keV cm^(-2)s^(-1)sr^(-1)lower than that obtained by the Quiet method,and the linear correlation coefficient between the difference of SWCX and DXB obtained by the two methods in diffe rent energy band is close to-1,the diffe rences in magnetospheric SWCX can be fully attributed to the diffe rences in the fitted DXB.The difference between the two methods is most significant when the energy is less than 0.7 keV,which is also the main energy band of SWCX emission.In addition,the difference between the two methods is not related to the SWCX intensity and,to some extent,to solar wind conditions,because SWCX intensity typically va ries with the solar wind.In summary,both methods are robust and reliable,and should be considered based on the best available options.

SMILE soft X-ray Imager flight model CCD370 pre-flight device characterisation

Throughout the SMILE mission the satellite will be bombarded by radiation which gradually damages the focal plane devices and degrades their performance.In order to understand the changes of the CCD370s within the soft X-ray Imager,an initial characterisation of the devices has been carried out to give a baseline performance level.Three CCDs have been characterised,the two flight devices and the flight spa re.This has been carried out at the Open University in a bespo ke cleanroom measure ment facility.The results show that there is a cluster of bright pixels in the flight spa re which increases in size with tempe rature.However at the nominal ope rating tempe rature(-120℃) it is within the procure ment specifications.Overall,the devices meet the specifications when ope rating at -120℃ in 6 × 6 binned frame transfer science mode.The se rial charge transfer inefficiency degrades with temperature in full frame mode.However any charge losses are recovered when binning/frame transfer is implemented.

Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.