Effects of sphincter of Oddi motility on the formation of cholesterol gallstones

AIM: To investigate the mechanisms and effects of sphincter of Oddi(SO) motility on cholesterol gallbladder stone formation in guinea pigs.METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group(n = 10) and the cholesterol gallstone group(n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor(CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR(q RT-PCR) and serum vasoactive intestinal peptide(VIP), gastrin, and cholecystokinin octapeptide(CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Nature-inspired design of droplet-synthesized polymeric nanoelectrode for photoelectrochemical microRNA sensing within single cells

Nanoelectrodes have been shown to be powerful tools for nanoscopic research on single entities,deepening the understanding of heterogeneity and stochastics for single molecules,nanoparticles and cells[1–3].However,despite their importance,current nanoelectrode preparations are highly restrained to flame/electrochemical etching,metal sputtering,electrochemical deposition,etc.[3],resulting in a limited range of materials(mainly gold,platinum and carbon)for potential-resolved detection of redox-active species(Table S1 online).The enrichment of preparation methods to introduce novel materials and mechanisms should prove significant for the development of nanoelectrodes.

Aggregation-induced delayed electrochemiluminescence of organic dots in aqueous media

Full utilization of the excited species at both singlet states(1R*)and triplet states(3R*)is crucial to improving electrochemiluminescence(ECL)efficiency but is challenging for organic luminescent materials.Here,an aggregation-induced delayed ECL(AIDECL)active organic dot(OD)containing a benzophenone acceptor and dimethylacridine donor is reported,which shows high ECL efficiency via reverse intersystem crossing(RISC)of non-emissive 3R*to emissive 1R*,overcoming the spin-forbidden radiative decay from 3R*.By introducing dual donor-acceptor pairs into luminophores,it is found that nonradiative pathway could be further suppressed via enhanced intermolecular weak interactions,and multiple spin-up conversion channels could be activated.As a consequence,the obtained OD enjoys a 6.8-fold higher ECL efficiency relative to the control AIDECL-active OD.Single-crystal studies and theoretical calculations reveal that the enhanced AIDECL behaviors come from the acceleration of both radiative transition and RISC.This work represents a major step towards purely organic,high-efficiency ECL dyes and a direction for the design of next-generation ECL dyes at the molecular level.

硅太阳能电池供能的有机电化学晶体管光电子器件

越来越多的研究将有机电化学晶体管(OECT)用于新颖的电学设备,然而这些设备天然需要两个仪器电源,不利于将其应用于对能源供应有严格要求的便携和可穿戴体系.本文通过将单晶硅太阳能电池组装到OECT的回路中并以光作为燃料,构建了自供能和光调控功能的有机光电化学晶体管(OPECT)光电子器件.以基于聚(3,4-乙烯二氧噻吩)-聚(苯乙烯磺酸酯)(PEDOT:PSS)的耗尽型和增强型OECT为例,我们设计了不同的光寻址结构并系统地研究和比较了相应的特性.通过合适的光调制,我们实现了不同的器件行为,且这些器件表现出优异的性能.在应用层面,我们设计了光逻辑电路,其不同的特性可以通过相应的辐照度来调控;此外,我们展示了光控的OECT单极逆变器,并根据系统的能源供应和阻抗进行了优化.本工作代表着新型的OPECT光电子器件,合理地将其与柔性基底和太阳能电池组装有望应用于便携和可穿戴器件领域.

High-gain signal-on PEDOT:PSS organic photoelectrochemical transistor biosensing modulated by a MXene/MOFs/NiO Schottky heterojunction

Herein we report a high-gain signal-on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(PEDOT:PSS)organic electrochemical transistor(OECT)biosensing using an accumulation-mode PEDOT:PSS OECT modulated by a light-fueled MXene/MOFs/Ni O Schottky heterojunction.In such a system,the MXene/MOFs/Ni O Schottky heterojunction exhibited superior gating effect,as it not only enabled the fast-directional charge transfer but also guaranteed the maximal accessibility of the electrolyte to topped 2D MXene with large surface area.In linkage with a bi-enzyme cascade system,the quinone derivatives produced by the cascade reaction of alkaline phosphatase(ALP)and tyrosinase(TYR)could serve as effective electron acceptors for the representative Ti_(3)C_(2)/PCN-224/Ni O heterojunction,underpinning an innovative method for sensitive detection of ALP activity with a low detection limit of 0.001 U L^(-1).Remarkably,the as-developed system demonstrated a remarkable current gain as high as near 10^(4),which to our knowledge is the highest one among existing OECT biosensory devices.This work represents a generic protocol to develop the novel signal-on PEDOT:PSS OECT platform towards biochemical detection and beyond.

Emerging advances in plasmonic nanoassemblies for biosensing and cell imaging

Integrating discrete plasmonic nanoparticles into assemblies can induce plasmonic coupling that produces collective plasmonic properties,which are not available for single nanoparticles.Theoretical analysis revealed that plasmonic coupling derived from assemblies could produce stronger electromagnetic field enhancement effects.Thus,plasmonic assemblies enable better performance in plasmon-based applications,such as enhanced fluorescence and Raman effects.This makes them hold great potential for trace analyte detection and nanomedicine.Herein,we focus on the recent advances in various plasmonic nanoassembles such as dimers,tetramers,and core-satellite structures,and discuss their applications in biosensing and cell imaging.The fabrication strategies for self-assembled plasmonic nanostructures are described,including top-down strategies,self-assembly methods linked by DNA,ligand,polymer,amino acid,or proteins,and chemical overgrowth methods.Thereafter,their applications in biosensor and cell imaging based on dark-field imaging,surface-enhanced Raman scattering,plasmonic circular dichroism,and fluorescence imaging are discussed.Finally,the remaining challenges and prospects are elucidated.

Single-particle detection of cholesterol based on the host-guest recognition induced plasmon resonance energy transfer

Plasmon resonance energy transfer(PRET) occurs between the plasmonic nanoparticles(NPs) and organic dyes forming donor-acceptor pairs, which has great potential in quantitative analytical chemistry because of its excellent sensitivity under dark-field microscopy(DFM). Herein, we introduce supramolecular β-cyclodextrin(β-CD) to design a host-guest recognition plasmonic nano-structure modified gold nanoparticles(GNPs), while GNPs and rhodamine molecule(RB) act as the donor and acceptor, respectively. In the presence of the target cholesterol, due to the stronger binding of cholesterol with β-CD, RB molecules are released, inducing the inhibition of PRET, as well as the increase of the scattering intensity of GNPs.The proposed strategy achieves a linear range from 0.02 μmol/L to 2.0 μmol/L for cholesterol detection,and reaches a limit of detection(LOD) of 6.7 nmol/L. This host-guest recognition strategy can easily integrate receptor-donor pair into one nanoparticle, which simplifies the construction of the PRET platform,and further provides an effective approach for PRET-based analytical applications. Afterwards, the proposed PRET strategy was successfully applied for the detection of cholesterol in serum samples with high sensitivity and specificity. The proposed method provides an effective clinically potential means for the detection of cholesterol and other disease-related biomarkers.

Nanokit coupled electrospray ionization mass spectrometry for analysis of angiotensin converting enzyme 2 activity in single living cell

Angiotensin-converting enzyme 2(ACE2) is not only an enzyme but also a functional receptor on cell membrane for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Here, the activity of ACE2 in single living cell is firstly determined using a nanokit coupled electrospray ionization mass spectrometry(nanokit-ESI-MS). Upon the insertion of a micro-capillary into the living h ACE2-CHO cell and the electrochemical sorting of the cytosol, the target ACE2 enzyme hydrolyses angiotensin II inside the capillary to generate angiotensin 1-7. After the electrospray of the mixture at the tip of the capillary, the product is differentiated from the substrate in molecular weight to achieve the detection of ACE2 activity in single cells. The further measurement illustrates that the inflammatory state of cells does not lead to the significant change of ACE2 catalytic activity, which elucidates the relationship between intracellular ACE2 activity and inflammation at single cell level. The established strategy will provide a specific analytical method for further studying the role of ACE2 in the process of virus infection, and extend the application of nanokit based single cell analysis.

Cell mechanics and energetic costs of collective cell migration under confined microchannels

Mechanical force between cells relates to many biological processes of cell development.The cellular collective migration comes from cell-cell cooperation,and studying the intercellular mechanical properties helps elucidate collective cell migration.Herein,we studied cell-cell junctions,intercellular tensile force and the related cellular energetic costs in confined microchannels.Using the intercellular force sensor,we found that cells adapt to different confinement environments by regulating intercellular force,and thereby the relationship between collective cell migration and cell-cell junction were verified.Through the observation of cell orientation,actomyosin contractility,energetic costs,and glucose uptake,we can make a reasonable explanation of cell-force driven migration in different confined environments.Under highly confined conditions,the intercellular force and energetic costs are greater,and the cell orientation is more orderly.The collective migration behavior in confined spaces is closely related to the intercellular force and energetic costs,which is helpful to understand the collective migration behaviors in various confined spaces.

Real-Time and Spatial Electroanalysis of Biomolecules in One Living Cell Using Liquid-Phase Modified Nanopipette

The well-developed solid-phase modified strategy at the electrode has enabled the preparation of biosensors for the detection of multiple analytes,even in single living cells.However,limited assay elements can be modified at the solid surface,restricting the types of molecules that can be analyzed and the sensitivity of detection.Here,a novel liquid-phase modified strategy at the tip of a nanopipette is designed to realize real-time and local analysis of biomolecules inside the cell that are barely detectable using solid-phase modified nanoelectrodes.This design utilizes the nanotip structure at a platinized carbon open nanopipette to stably retain a nanodroplet that contains the required reagents with high reactivity for the assay of the target analyte.The generated hydrogen peroxide is electrochemically quantified at the Pt layer to carry out the real-time measurement in a living cell with a spatial resolution of 70 nm.Taking advantage of highly spatial and real-time detection,uneven distribution of sphingomyelinase(SMase)in the living CT26 cell is unprecedentedly shown to exhibit the significance in the establishment of liquid-phase modified nanopipette.This new modification strategy opens up a new direction for sensor design and consequently advances the development of biosensors in the chemical and biological research.

Trace Ir(Ⅲ)complex enhanced electrochemiluminescence of AIE-active Pdots in aqueous media

Trace Ir(Ⅲ)complex enhanced aggregation-induced electrochemiluminescence(AIECL)of poly-tetraphenylethene(p TPE)in aqueous media was investigated for the first time.The poly-TPE end-capped by Ir(Ⅲ)complex(Ir@p TPE)and its corresponding model polymer poly-TPE(Ph@pTPE)could be synthesized by Suzuki coupling polymerization reaction of 1,2-bis(4-bromophenyl)-1,2-diphenylethene(M-1)with 1,2-diphenyl-1,2-bis(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethene(M-2)and the continuous Suzuki coupling end-capped reaction of poly-TPE-pinacol boronate with(pq)2 Ir(pico)Br and bromobenzene,respectively.Subsequently,the corresponding Ir@p TPE Pdots and Ph@p TPE Pdots encapsulated with poly(styrene-co-maleicanhydride)(PSMA)could be obtained by nanoprecipitation method.Compared with Ph@p TPE Pdots,the Ir@p TPE Pdots with a trace amount of Ir(Ⅲ)complex(1.34‰of Ir(Ⅲ)content,wt)could exhibit 9.9-fold enhancement of the electrochemiluminescence(ECL)signal for visual emission.This work provided a novel strategy on designing highly efficient ECL materials based on trace Ir(Ⅲ)-end capping AIE-active polymer dots.

Degradable Hybrid CuS Nanoparticles for Imaging-Guided Synergistic Cancer Therapy via Low-Power NIR-II Light Excitation

Near-infrared(NIR)-II light-excitable photonic agents capable of generating tumor hyperthermia and cytotoxic free radicals are promising for synergistic phototherapy of tumors.However,the lack of NIR-II excitable agents makes it challenging to achieve combinational tumor phototherapy.Here,the authors have reported on a tumor-targeting and degradable hybrid copper sulfide(CuS)nanoparticle(AIBA@CuS-FA)via loading a hydrophilic Azo initiator(AIBA)into an amphiphilic lipid-encapsulating CuS nanoparticle.AIBA@CuS-FA shows high photothermal conversion efficiency(PCE≈47.5%)at 1064 nm,enabling heat production to trigger tumor hyperthermia and thermal decomposition of AIBA into cytotoxic free alkyl radicals upon irradiation with a 1064-nm laser under low-power density(0.5 W/cm2).Moreover,alkyl radicals can drive degradation of AIBA@CuS-FA and embedded CuS nanodisks,releasing Cu^(2+)ions that can catalyze a Fenton-like reaction for hydroxyl radical(•OH)production to promote tumor therapy.Findings demonstrate promise for combinational photothermal therapy(PTT),oxygen-independent alkyl radical therapy,and chemodynamic therapy(CDT)of tumors.

A robust watermarking algorithm based on QR factorization and DCT using quantization index modulation technique

We propose a robust digital watermarking algorithm for copyright protection.A stable feature is obtained by utilizing QR factorization and discrete cosine transform(DCT) techniques,and a meaningful watermark image is embedded into an image by modifying the stable feature with a quantization index modulation(QIM) method.The combination of QR factorization,DCT,and QIM techniques guarantees the robustness of the algorithm.Furthermore,an embedding location selection method is exploited to select blocks with small modifications as the embedding locations.This can minimize the embedding distortion and greatly improve the imperceptibility of our scheme.Several standard images were tested and the experimental results were compared with those of other published schemes.The results demonstrate that our proposed scheme can achieve not only better imperceptibility,but also stronger robustness against common signal processing operations and lossy compressions,such as filtering,noise addition,scaling,sharpening,rotation,cropping,and JPEG/JPEG2000 compression.

Nanoelectrochemical architectures for high-spatial-resolution single cell analysis

The analysis of single cells instead of cell populations is important for characterizing cellular heterogeneity and elucidating the cellular signalling pathways. Nanoelectrodes have emerged as an increasingly important tool for biomolecule analyses at the single-cell level with high spatial or temporal resolution. Various electrochemical methods, such as amperometry and scanning electrochemical microscopy(SECM), have been applied. Research to date has focused on the development of new nanoelectrochemical architectures, such as arrays, to achieve higher spatial resolution and faster analysis rates for single-cell analysis. In this review, the fabrication of these new nanoelectrochemical architectures and their applications in high spatial resolution single-cell analyses are discussed. The recent progress of Chinese researchers is highlighted.

Wireless Electrochemical Visualization of Intracellular Antigens in Single Cells

Electrochemical microscopy has been developed in the past decades for imaging biomolecules in single cells;however,electrochemical visualization of an intracellular protein in one cell is difficult.Herein,for the first time,we have developed a model whereby the protein,KDM1/LSD1 antigen,in the nucleus of a single MCF 7 cell could be visualized using wireless bipolar electrochemiluminescence(BPEECL).Submicron-sized,single-walled carbon nanotubes were linked with anti-KDM1/LSD1 antibodies and loaded into the cells for the recognition of the corresponding KDM1/LSD1 antigen.With a low electric field of 1000 V/cm,L012,a luminol analog,was oxidized electrochemically at one end of the nanotube that emitted light for the wireless visualization of its location.The significant drop in the applied voltage permitted the observation of apparent ECL emission inside the nucleus of a single cell,supporting the electrochemical imaging of intracellular KDM1/LSD1 antigen at a single-cell level.This work solves a long-standing task in the field of electroanalysis for intracellular wireless visualization,which should advance the development of electrochemistry in single-cell analysis.

A Supersmall Single-Cell Nanosensor for Intracellular K^(+) Detection

Intracellular potassium ions(K^(+))play pivotal roles in many physiological processes.Several K^(+)sensors have been developed for probing cellular K^(+)fluctuations.Nevertheless,the existing solutions are incompatible and impractical for intracellular K^(+)probing.Herein,we report a supersmall biomimetic K^(+)nanosensor to serve as a transmembrane vector capable of electrochemically detecting intracellular K^(+)in a minimally invasive manner.

Photo-stability and Photo-damage of SPASER Nanoparticles under Nanosecond Pulsed-laser

Comprehensive Summary SPASER nanoparticle(NP),with small size,ultranarrow spectral-line and good biocompatibility,is a potential biomedical nanoprobe.However,owning to the striking light absorption capacity of Au-resonator,huge energy could accumulate under strong pumping-laser,which would lead to poor photo-stability and unexpected photo-damage to SPASER NP,and is harmful to its future practical application but hasn't been systematically studied in experiment.

An activatable ratiometric near-infrared fluorescent probe for hydrogen sulfide imaging in vivo

Ratiometric fluorescent probes hold great promise for in vivo imaging;however,stimuli-activatable ratiometric probes with fluorescence emissions in near-infrared(NIR)region are still very few.Herein,we report a hydrogen sulfide(H_2S)-activatable ratiometric NIR fluorescent probe(1-SPN)by integrating a H_2S-responsive NIR fluorescent probe 1 into a H_2S-inert poly[2,6-(4,4-bis-(2-ethylhexyl)-4 H-cyclopenta[2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)](PCPDTBT)-based NIR semiconducting polymer nanoparticle(SPN).1-SPN shows"always on"PCPDTBT fluorescence at 830 nm and weak probe 1 fluorescence at 725 nm under excitation at 680 nm.The ratio of NIR fluorescence intensities between 725 and 830 nm(I_(725)/I_(830))is small.Upon interaction with H_2S,the fluorescence at 725 nm is rapidly switched on,resulting in a large enhancement of I_(725)/I_(830),which is allowed for sensitive visualization and quantification of H_2S concentrations in living cells.Taking advantage of enhanced tissue penetration depth of NIR fluorescence,1-SPN is also applied for real-time ratiometric fluorescence imaging of hepatic and tumor H_2S in living mice.This study demonstrates that activatable ratiometric NIR fluorescent probes hold great potential for in vivo imaging.

Bioanalysis in single cells: current advances and challenges

Cells, basic units of living structures and functions, build up a complicated small world, and their order and complexity resemble a small universe. The detailed understanding and elucidation of the matter transport and energy conversion mechanisms within a single cell will expand our knowledge about the origin and evolution of life, the disease mechanisms and much more. In past decades, single-cell analysis has been rapidly and significantly improved and various methodologies have been developed to reveal the complexity of mass, energy, and information within single cells. In this review, we focused on the methods developed in recent years for single-cell analysis, including electrochemical method, optical method, and mass spectrometry method. We reviewed the recent advances and representative studies in this research field, and also discussed the strengths and limitations of each method. Finally, we presented the existing technical challenges and further directions for single-cell analysis.

Measuring the number concentration of arbitrarily-shaped gold nanoparticles with surface plasmon resonance microscopy

Molar concentration of gold nanoparticles is one of the most critical parameters of gold colloids in order to develop their applications in sensing, diagnostics and nanomedicine. Previous methods often stand just for gold nanoparticles with regular shape and narrow size distribution. In the present work, we proposed an absolute quantification method that determined the molar concentration of gold nanoparticles with arbitrary shapes and polydisperse sizes. This approach involved the real time monitoring and counting of individual nanoparticles collision events, from which the quantification of molar concentration was achieved using a theoretical model consisting of Fiek＇s laws of diffusion and Stokes-Einstein equation. The determination of spherical gold nanoparticles concentration resulted in excellent agreement with traditional spectrometry method. It was further demonstrated that the present approach can be expanded to determine the molar concentration of gold nanoparticles with arbitrary shapes and poly-diversed distributions.