Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks

Covalent organic frameworks(COFs),a rapidly developing category of crystalline conjugated organic polymers,possess highly ordered structures,large specific surface areas,stable chemical properties,and tunable pore microenvironments.Since the first report of boroxine/boronate ester-linked COFs in 2005,COFs have rapidly gained popularity,showing important application prospects in various fields,such as sensing,catalysis,separation,and energy storage.Among them,COFs-based electrochemical(EC)sensors with upgraded analytical performance are arousing extensive interest.In this review,therefore,we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry,with special emphasis on their usages in the fabrication of chemical sensors,ions sensors,immunosensors,and aptasensors.Notably,the emerged COFs in the electrochemiluminescence(ECL)realm are thoroughly covered along with their preliminary applications.Additionally,final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors,as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

A Generic Strategy to Create Mechanically Interlocked Nanocomposite/Hydrogel Hybrid Electrodes for Epidermal Electronics

Stretchable electronics are crucial enablers for next-generation wearables intimately integrated into the human body.As the primary compliant conductors used in these devices,metallic nanostructure/elastomer composites often struggle to form conformal contact with the textured skin.Hybrid electrodes have been consequently developed based on conductive nanocomposite and soft hydrogels to establish seamless skin-device interfaces.However,chemical modifications are typically needed for reliable bonding,which can alter their original properties.To overcome this limitation,this study presents a facile fabrication approach for mechanically interlocked nanocomposite/hydrogel hybrid electrodes.In this physical process,soft microfoams are thermally laminated on silver nanowire nanocomposites as a porous interface,which forms an interpenetrating network with the hydrogel.The microfoam-enabled bonding strategy is generally compatible with various polymers.The resulting interlocked hybrids have a 28-fold improved interfacial toughness compared to directly stacked hybrids.These electrodes achieve firm attachment to the skin and low contact impedance using tissue-adhesive hydrogels.They have been successfully integrated into an epidermal sleeve to distinguish hand gestures by sensing mus-cle contractions.Interlocked nanocomposite/hydrogel hybrids reported here offer a promising platform to combine the benefits of both materials for epidermal devices and systems.

Individual dynamics and local heterogeneity provide a microscopic view of the epidemic spreading

The COVID-19 pandemic has caused severe global disasters,highlighting the importance of understanding the details and trends of epidemic transmission in order to introduce efficient intervention measures.While the widely used deterministic compartmental models have qualitatively presented continuous “analytical” insight and captured some transmission features,their treatment usually lacks spatiotemporal variation.Here,we propose a stochastic individual dynamical(SID)model to mimic the random and heterogeneous nature of epidemic propagation.The SID model provides a unifying framework for representing the spatiotemporal variations of epidemic development by tracking the movements of each individual.Using this model,we reproduce the infection curves for COVID-19 cases in different areas globally and find the local dynamics and heterogeneity at the individual level that affect the disease outbreak.The macroscopic trend of virus spreading is clearly illustrated from the microscopic perspective,enabling a quantitative assessment of different interventions.Seemingly,this model is also applicable to studying stochastic processes at the “meter scale”,e.g.,human society’s collective dynamics.

Seminal Plasma Biochemical Components Mediate the Inverse Association of Microcystin Exposure with Sperm Motility:A Mediation Analysis in Chinese Men

Epidemiological studies suggest a global decline in male fertility, which accounts for approximately50% of infertility cases in couples. Male infertility is a multifactorial and complex issue that may arise due to congenital, acquired, idiopathic, or other unknown factors[1].

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

CoFe_(2)O_(4) decorated graphene/C_(18)-functionalized mesoporous silica nanocomposites prepared for magnetic enrichment and electrochemical detection of promethazine in beef

Promethazine(PHZ)is used as a sedative in veterinary medicine,and its residue can threaten the health of human.The electrochemical detection of PHZ is suitable method for application in the field.However,the traditional electroanalysis is difficult to perform directly in meat samples due to matrix interference.This work integrates magnetic solid-phase extraction and differential pulse voltammetry for highly sensitive and selective determination of PHZ in beef and beef liver for the first time.CoFe_(2)O_(4)/graphene coated with C_(18)-functionalized mesoporous silica(MG@mSiO_(2)-C_(18))is synthesized as dispersed magnetic adsorbent to extract PHZ.Magnetic glassy carbon electrode modified with nitrogen-doped hollow carbon microspheres(HCM)attracts the MG@mSiO_(2)-C_(18)with PHZ,and directly detects the PHZ without elution procedure.MG@mSiO_(2)-C_(18)can separate PHZ to avoid the interference of impurities on following detection,and also concentrate PHZ on magnetic electrode.Additionally,the electrode modification with HCM can amplify the electrochemical signal of PHZ.Finally,the integrated PHZ determination method exhibits a wide linear range from 0.08μmol/L to 300μmol/L with a low limit of detection of 9.8 nmol/L.The beef sample analysis presents excellent recovery,demonstrating that this protocol is promising for the rapid and onsite detection of PHZ in real meat samples。

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

Inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the intestine.Excessive pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in IBD.Here,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the lesion.DCMP can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting pyroptosis.It also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with colitis.This work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

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.

Recent advances in electrogenerated chemiluminescence biosensing methods for pharmaceuticals

Electrogenerated chemiluminescence(electrochemiluminescence, ECL) generates species at electrode surfaces, which undergoes electron-transfer reactions and forms excited states to emit light. It has become a very powerful analytical technique and has been widely used in such as clinical testing, biowarfare agent detection, and pharmaceutical analysis. This review focuses on the current trends of molecular recognition-based biosensing methods for pharmaceutical analysis since 2010. It introduces a background of ECL and presents the recent ECL developments in ECL immunoassay(ECLIA), immunosensors, enzyme-based biosensors, aptamer-based biosensors, and molecularly imprinted polymers(MIP)-based sensors. At last, the future perspective for these analytical methods is briefly discussed.

Visualization analysis of lecithin in drugs based on electrochemiluminescent single gold microbeads

Fast and high-throughput determination of drugs is a key trend in clinical medicine.Single particles have increasingly been adopted in a variety of photoanalytical and electroanalytical applications,and microscopic analysis has been a hot topic in recent years,especially for electrochemiluminescence(ECL).This paper describes a simple ECL method based on single gold microbeads to image lecithin.Lecithin reacts to produce hydrogen peroxide under the successive enzymatic reaction of phospholipase D and choline oxidase.ECL was generated by the electrochemical reaction between a luminol analog and hydrogen peroxide,and ECL signals were imaged by a camera.Despite the heterogeneity of single gold microbeads,their luminescence obeyed statistical regularity.The average luminescence of 30 gold microbeads is correlated with the lecithin concentration,and thus,a visualization method for analyzing lecithin was established.Calibration curves were constructed for ECL intensity and lecithin concentration,achieving detection limits of 0.05 m M lecithin.This ECL imaging platform based on single gold microbeads exhibits outstanding advantages,such as high throughput,versatility and low cost,and holds great potential in disease diagnostics,environmental monitoring and food safety.

Luminescence and ESR Studies of CaS：Dy Phosphor

CaS phosphor activated with Dy ions is prepared by the solid-state diffusion method. The phosphor is characterized by x-ray powder diffraction, thermogravimetric analysis and photoiuminescence. Defect centres formed in CaS：Dy are studied using the technique of electron spin resonance. The thermoluminescence glow curve shows peaks at around 117℃ and 345℃. Irradiated CaS：Dy exhibits ESR lines due to defect centres. The thermal annealing behaviour of one of the defect centres appears to correlate with the TL peaks at 117℃ and 345℃. This centre is characterized by an isotropic g-value of 2.0035 and is assigned to an F^＋ centre.

A DNA-based nanocarrier for efficient cancer therapy

The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread(CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT.Atomic force microscopy(AFM)characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm.The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis,as large the molecular-weight(polymeric)DNA-NT did not split into constituting strands under applied current and voltage.The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration(512 nM)with a viability of 92%as evidence of its biocompatibility for drug delivery.MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization.The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT(from DNA-NT),as illustrated in confocal images.Therefore,in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis(72.7%)with CPT-DNA-NT(compared to free CPT;64.4%).CPT-DNA-NT,being poly-anionic,showed enhanced endocytosis via scavenger receptors.

Microwave-assisted sol-gel synthesis of hydroxyapatite nanoparticles

A rapid sol-gel method for preparing hydroxyapatite nanoparticles(nHAP) has been developed. Three different sets of experimental conditions, in terms of solvents(water and ethanol), synthesis temperatures(25, 40 and 60℃), and microwave irradiation(on and off) were explored. Crystal phase composition, functional groups and morphology of the products were characterized by thermogravimetric analysis(TGA), X-ray diffraction(XRD), Fourier transform infrared spectroscopy(FT-IR), scanning electron microscopy(SEM) and transmission electron microscopy(TEM). The solvent and temperature were optimized based on product properties. Most importantly, the microwave-assisted method(with little to no ageing necessary) was much faster than the conventional methods(with slow ageing processes needing from hours to days), while affording pure nHAP with virtually identical morphological and structural properties. This study represents a practical application of the powerful microwave technique in synthesis of nHAP, offering guidance on the selection of optimum experiment conditions.

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical step followed by annealing with various staple strands to make stiff DNAtriangles. Atomic force microcopy(AFM), native polyacrylamide gel electrophoresis(PAGE), UVanalysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 mm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane(500 bp level) with the loss of electrophoretic mobility during the PAGE(native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNANWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%) compared to the apoptosis(7%)induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC_(50) of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC_(50) of 51.2 n M.Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2) compared with the control cell line.

Corrigendum to“The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors”[Journal of Pharmaceutical Analysis volume 11(2021)174e182]

The authors regret to inform that Figs.4,6,and 7 in the original article were wrongly selected.The corrected figures appear below:The authors would like to apologize for any inconvenience caused.

Spherical Nucleic Acid-Amplified Digital Flow Cytometric Bead Assay for the Ultrasensitive Detection of Protein and Exosome

Comprehensive Summary,Most conventional digital bioassays rely on the use of fully-sealed microchambers as independent units to compartmentalize the target molecules and the signal generation reaction,which require specialized equipment or proprietary reagents/consumables.Herein,we report a microchamber-free and spherical nucleic acid(SNA)-amplified digital flow cytometric bead assay(dFBA)for ultrasensitive protein and exosome analysis with simple workflows,easily accessible instruments/reagents,and high discriminating ability towards the fluorescence-positive and fluorescence-negative beads.In this dFBA,microbeads are employed as independent carriers to anchor the single target molecule-initiated signal amplification reaction,avoiding the use of sealed droplets or microwell microchambers.Meanwhile,antibody-functionalized SNAs(FSNAs)with a high density of DNA probes act as a bridge for efficiently amplified target-to-DNA signal conversion,which allows the use of DNA-based rolling circle amplification(RCA)as the fluorescence signal amplification technique to quantify non-nucleic acid targets.Even a single target-induced on-bead RCA and fluorescence enriching are sufficient to make the target-loaded bead bright enough to be clearly discriminated from the negative ones just by use of a most common flow cytometer(FCM).This dFBA has successfully realized the digital analysis of ultralow levels of protein and exosome biomarkers,enlarging the toolbox of digital bioassays for clinical applications.

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.

Novel computer-assisted approach to quick prediction and optimization of gradient separation for online enrichment-reversed phase liquid chromatography tandem system

An algorithm capable of predicting and optimizing the gradient separation of LC×LC system was developed in this paper.Two groups of structural analogues,five ginsenosides as well as eight bisphenols,which were difficult to discriminate in routine analysis,were used to verify the effectiveness of the proposed algorithm in fast separation optimization.Average errors of retention times below 1%were found in the retention prediction for all types of gradient programs,implying that the theory could lead to high quality in prediction of the retention times under gradients elution.Meanwhile,84%of relative average deviations(RADs)between the predicted peak width and the measured ones were less than 20%.The larger deviation occurred at the time when the peak appeared while the gradient of the mobile phase changed,which led the deviations increased to 20%–42%.In all,method development and optimization for LC×LC tandem system was realized by the homemade user-friendly software.The present protocol may turn on great opportunities for the convenient method development in analysis of trace structural analogues in environmental,food and biological samples.

Stretchable,breathable,and washable epidermal electrodes based on microfoam reinforced ultrathin conductive nanocomposites

Stretchable epidermal electronics allow conformal interactions with the human body for emerging applications in wearable health monitoring and therapy.Stretchable devices are commonly constructed on submillimeter-thick elastomer substrates with limited moisture permeability,thereby leading to unpleasant sensations during long-term attachment.Although the ultrathin elastomer membrane may address this problem,the mechanical robustness is essentially lost for direct manipulations and repetitive uses.Here,we report a stretchable,breathable,and washable epidermal electrode of microfoam reinforced ultrathin conductive nanocomposite(MRUCN).The new architecture involves ultrathin conductive silver nanowire nanocomposite features supported on a porous elastomeric microfoam substrate,which exhibits high moisture permeability for pleasant perceptions during epidermal applications.As-prepared epidermal electrodes show excellent electronic conductivity(8440 S·cm^(-1)),high feature resolution(~50μm),decent stretchability,and excellent durability.In addition,the MRUCN retains stable electrical properties during washing to meet the hygiene requirements for repetitive uses.The successful implementation in an integrated electronic patch demonstrates the practical suitability of MRUCN for a broad range of epidermal electronic devices and systems.

COVID-19 and liver dysfunction in children:Current views and new hypotheses

Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been demonstrated.However,there are few reports and studies on COVID-19 related liver injury in children,and the data are scattered.So that many contradictions have arose.This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient outcomes.Therefore,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak.The etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver injury.In summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.