A solution-processed n-type conducting polymer with ultrahigh conductivity.

Conducting polymers (CPs) with high conductivity and solution processability have made great advances since the pioneering work on doped polyacetylene1-3, thus creating the new field of 'organic synthetic metals,4. Various high-performance CPs have been realized, which enable the applications of several organic electronic devices5,6. Nevertheless, most CPs exhibit hole-dominant (p-type) transport behaviour7,8, whereas the development of n-type analogues lags far behind and only a few exhibit metallic state, typically limited by low doping efficiency and ambient instability. Here we present a facilely synthesized highly conductive n-type polymer poly(benzodifurandione) (PBFDO). The reaction combines oxidative polymerization and in situ reductive n-doping, greatly increasing the doping efficiency, and a doping level of almost 0.9 charges per repeating unit can be achieved. The resultant polymer exhibits a breakthrough conductivity of more than 2,000 S cm-1 with excellent stability and an unexpected solution processability without extra side chains or surfactants. Furthermore, detailed investigations on PBFDO show coherent charge-transport properties and existence of metallic state. The benchmark performances in electrochemical transistors and thermoelectric generators are further demonstrated, thus paving the way for application of the n-type CPs in organic electronics.

Solid-State Glass Nanopipettes: Functionalization and Applications.

Solid-state glass nanopipettes provide a promising confined space that offers several advantages such as controllable size, simple preparation, low cost, good mechanical stability, and good thermal stability. These advantages make them an ideal choice for various applications such as biosensors, DNA sequencing, and drug delivery. In this review, we first delve into the functionalized nanopipettes for sensing various analytes and the methods used to develop detection means with them. Next, we provide an in-depth overview of the advanced functionalization methodologies of nanopipettes based on diversified chemical kinetics. After that, we present the latest state-of-the-art achievements and potential applications in detecting a wide range of targets, including ions, molecules, biological macromolecules, and single cells. We examine the various challenges that arise when working with these targets, as well as the innovative solutions developed to overcome them. The final section offers an in-depth overview of the current development status, newest trends, and application prospects of sensors. Overall, this review provides a comprehensive and detailed analysis of the current state-of-the-art functionalized nanopipette perception sensing and development of detection means and offers valuable insights into the prospects for this exciting field.

Modification of Food Allergy on the Associations between Early Life Exposure to Size-Specific Particulate Matter and Childhood Allergic Rhinitis.

Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 µg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 µg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.

An n-Type Open-Shell Conjugated Polymer with High-Spin Ground-State and High Intrinsic Electrical Conductivity.

Open-shell conjugated polymers with a high intrinsic conductivity and high-spin ground state hold considerable promise for applications in organic electronics and spintronics. Herein, two novel acceptor-acceptor (A-A) conjugated polymers based on a highly electron-deficient quinoidal benzodifurandione unit have been developed, namely DPP-BFDO-Th and DPP-BFDO. The incorporation of the quinoidal moiety into the polymers backbones enables deeply aligned lower-lying lowest unoccupied molecular orbital (LUMO) levels of below -4.0 eV. Notably, DPP-BFDO exhibits an exceptionally low LUMO (-4.63 eV) and a high-spin ground state characterized by strong diradical characters. Moreover, a self-doping through intermolecular charge-transfer is observed for DPP-BFDO, as evidenced by X-ray photoelectron spectroscopy (XPS) studies. The high carrier concentration in combination with a planar and linear conjugated backbone yields a remarkable electrical conductivity (σ) of 1.04 S cm-1 in the "undoped" native form, ranking among the highest values reported for n-type radical-based conjugated polymers. When employed as an n-type thermoelectric material, DPP-BFDO achieves a power factor of 12.59 µW m-1 K-2. Furthermore, upon n-doping, the σ could be improved to 65.68 S cm-1. This study underscores the great potential of electron-deficient quinoidal units in constructing dopant-free n-type conductive polymers with a high-spin ground state and exceptional intrinsic conductivity.

Multiplex Assays of MicroRNAs by Using Single Particle Electrochemical Collision in a Single Run.

It is important to quantify multiple biomarkers in a single run due to the advantages of precious samples and diagnostic accuracy. Based on the distinguishability of two types of current signals from single particle electrochemical collision (SPEC), step-type current transients produced by Pt nanoparticles (PtNPs) catalyzed hydrazine oxidation and peak-type current transients produced by Ag nanoparticles (AgNPs) oxidation, a kind of multiplex immunoassay of target microRNAs (miRNA-21 and Let-7a) have been established during SPEC in a single run. When the single-stranded DNA (ssDNA1) that was perfectly complementary to miRNA-21 was coupled to the surface of PtNPs, the SPEC of PtNPs electrocatalysis was inhibited and the step-type current transients disappeared, while the single-stranded DNA (ssDNA2) that was perfectly complementary to Let-7a was coupled to the surface of AgNPs, the SPEC of AgNPs oxidation was inhibited, and the peak-type current transients disappeared, thus the signals were in the "off" state at this time. After that, miRNA-21 and Let-7a were added into solution, complementary base pairing disrupted the weak DNA-NP interaction and restored the electrocatalysis of PtNPs and the electrooxidation of AgNPs, and the step-type current signals and peak-type current signals were in the "on" state. Moreover, the frequencies from two different recovered signals (PtNPs catalysis and AgNPs oxidation) corresponded to the amount of added miRNA-21 and Let-7a, thus a multiplex immunoassay method for dual quantification of miRNA-21 and Let-7a in a single run was established.

Hairpin DNA-based electrochemical amplification strategy for miRNA sensing by using single gold nanoelectrodes.

A new sensor has been developed to detect miRNA-15 using nanoelectrodes and a hairpin DNA-based electrochemical amplification technique. By utilizing a complex DNA cylinder connected with hairpin DNA1, the sensor is able to absorb more methylene blue (MB) than simple double-stranded DNA. Another hairpin DNA2 is modified on an Au nanoelectrode surface and, when miRNA-15 is introduced, it triggers a chain reaction. This reaction unlocks two hairpins alternatively to polymerize into a complex structure that attaches more MB. The miRNA-15 is then replaced by DNA1 due to strand displacement reactions and continues to react with the next DNA2 to achieve circular amplification. The electrochemical signal from MB oxidation has a linear relationship with the miRNA-15 concentrations, making it possible to detect miRNA-15. Moreover, this method can be readily adapted for the detection of various other miRNA species. The newly devised nanosensor holds promising applications for the in vivo detection of miRNA-15 within biological systems, which is achieved by leveraging the advantageous characteristics of nanoelectrodes, including their low resistance-capacitance time constant, rapid mass transfer kinetics, and small diameter.

Discovery and characterisation of quinazolines and 8-Azaquinazolines as NLRP3 agonists with oral bioavailability in mice.

The NLRP3 inflammasome is a multiprotein complex that plays a critical role in activating the immune system in response to danger signals. Small molecule agonists of NLRP3 may offer clinical benefits in cancer immunology either as a monotherapy or in combination with checkpoint blockade, where it is hypothesised that their application can help to initiate an antitumor immune response. In this study, we report the discovery of quinazolines and 8-azaquinazolines as NLRP3 agonists and their chemical optimization to afford compounds with oral bioavailability in mice. We confirm that these compounds engage the NLRP3 inflammasome by verifying their dependence upon lipopolysaccharide (LPS) priming for cytokine release and the activation of Caspase-1. We further demonstrate pathway engagement through loss of activity in an NLRP3-knockout THP1 cell line. Based on their pharmacokinetic profile and biological activity, these compounds represent valuable tools to evaluate the therapeutic potential of NLRP3 activation in a pre-clinical setting.

Stochastic Collision Electrochemistry from Single Pt Nanoparticles: Electrocatalytic Amplification and MicroRNA Sensing.

Single-particle collisions have made many achievements in basic research, but challenges still exist due to their low collision frequency and selectivity in complex samples. In this work, we developed an "on-off-on" strategy based on Pt nanoparticles (PtNPs) that catalyze N2H4 collision signals on the surface of carbon ultramicroelectrodes and established a new method for the detection of miRNA21 with high selectivity and sensitivity. PtNPs catalyze the reduction of N2H4 on the surface of carbon ultramicroelectrodes to generate a stepped collision signal, which is in the "on" state. The single-stranded DNA paired with miRNA21 is coupled with PtNPs to form the complex DNA/PtNPs. Because PtNPs are covered by DNA, the electrocatalytic collision of N2H4 oxidation is inhibited. At this time, the signal is in the "off" state. When miRNA21 is added, the strong complementary pairing between miRNA21 and DNA destroys the electrostatic adsorption of DNA/PtNP conjugates and restores the electrocatalytic performance of PtNPs, and the signal is in the "on" state again. Based on this, a new method for detecting miRNA21 was established. It provides a new way for small-molecule sensing and has a wide range of applications in electroanalysis, electrocatalysis, and biosensing.

Nanopore-Based Single-Entity Electrochemistry for the Label-Free Monitoring of Single-Molecule Glycoprotein-Boronate Affinity Interaction and Its Sensing Application.

Nanopipettes provide a promising confined space that enables advances in single-molecule analysis, and their unique conical tubular structure is also suitable for single-cell analysis. In this work, functionalized-nanopore-based single-entity electrochemistry (SEE) analysis tools were developed for the label-free monitoring of single-molecule glycoprotein-boronate affinity interaction for the first time, and immunoglobulin G (IgG, one of the important biomarkers for many diseases such as COVID-19 and cancers) was employed as the model glycoprotein. The principle of this method is based on a single glycoprotein molecule passing through 4-mercaptophenylboronic acid (4-MPBA)-modified nanopipettes under a bias voltage and in the meantime interacting with the boronate group from modified 4-MPBA. This translocation and affinity interaction process can generate distinguishable current blockade signals. Based on the statistical analysis of these signals, the equilibrium association constant (κa) of single-molecule glycoprotein-boronate affinity interaction was obtained. The results show that the κa of IgG in the confined nanopore at the single-molecule level is much larger than that measured in the open system at the ensemble level, which is possibly due to the enhanced multivalent synergistic binding in the restricted space. Moreover, the functionalized-nanopore-based SEE analysis tools were further applied for the label-free detection of IgG, and the results indicate that our method has potential application value for the detection of glycoproteins in real samples, which also paves way for the single-cell analysis of glycoproteins.

Single-Molecule Investigation of the Protein-Aptamer Interactions and Sensing Application Inside the Single Glass Nanopore.

Solid-state nanopores offer a nanoconfined space for a single-molecule sensing strategy. Evaluating the behavior of proteins and protein-related interactions at the single-molecule level is becoming more and more important for a better understanding of biological processes and diseases. In this work, the aptamer-functionalized nanopore was prepared as the sensing platform for kinetic analysis of the carcinoembryonic antigen (CEA) with its aptamers, which is an important cancer biomarker. CEA molecules were captured by the aptamers immobilized on the inner surface of the nanopore, and there was a complicated interaction between the CEA molecules and the aptamer, which is the process of association and dissociation. This could be used to measure the dynamics of aptamer-protein interactions without labeling. The kinetic analysis could be evaluated at the single-molecule level to interpret the dissociation constants of the binding and dissociation processes. Results showed that the translocation of CEA molecules in a functionalized nanopore had a deep blockades degree and long duration compared with nanopore modified with bare gold, which could be used for CEA sensing. This protein and protein-related interaction we designed provides new insights for evaluating the binding affinity, which will be beneficial for protein sensing and immunoassays.

Anion-Doped Thickness-Insensitive Electron Transport Layer for Efficient Organic Solar Cells.

In organic solar cells, interfacial materials play essential roles in charge extraction, transportation, and collection. Currently, highly efficient and thickness-insensitive interfacial materials are urgently needed in printable large area module devices. Herein, water/alcohol-soluble conjugated polyelectrolyte PFNBT-Br, with medium bandgap based on benzothiadiazole, are doped by two alkali metal sodium salts, NaH2 PO2 , Na2 C2 O4 with different counter anions, to pursue high efficiency and thickness-insensitive electron-transport layers. Results show that the doping of electron-transport material can effectively promote the performance of the devices. Moreover, electron-transport layers doped by these salts with different counter anions show different behaviors in performances. Among which, the salt with oxalate anion C2 O4 2- (also named Ox2- ) shows much better device performance than the salt with hypophosphite anion (H2 PO2 - ), especially under the thick film condition (e.g., 50 nm). The greatly enhanced performances of interfacial material doped by Ox2- are due to reduced series resistance between the active layer material and the electrode, reduced dark-current, improved charge transport, and extraction efficiency, and decreased charge recombination for the devices at thick-film condition. These results demonstrated that n-doping could be a great potential strategy for making thickness-insensitive interfacial layers, besides, the performances can be further improved by carefully selecting salts.

In Situ SERS Monitoring of the Plasmon-Driven Catalytic Reaction by Using Single Ag@Au Nanowires as Substrates.

Single nanowires (NWs), as a kind of new surface-enhanced Raman scattering (SERS) substrates, have received extensive concern owing to their distinctive properties and distinct advantages. In this contribution, single Ag nanowires (AgNWs) and single Au-coated AgNWs (Ag@AuNWs) were fabricated by the laser-assisted pulling method and the galvanic replacement reaction, respectively. The prepared single Ag@AuNWs show both high SERS activity and catalytic activity through in situ monitoring and assessing the plasmon-driven surface-catalytic reaction of 4-nitrothiophenol (4-NTP) dimerizing to 4,4'-dimercaptoazobenzene and the reduction reaction of 4-NTP to para-aminothiophenol, respectively. It was found that the intensity of the Raman peak was affected greatly by the laser power, and the Raman peak could still be observed at 0.05% power under mild conditions (633 nm wavelength) in this single nanowire system. From the Raman spectrum, the SERS enhancement factor (EF) of 5.4 × 104 can be obtained, and the EF value of 1.3 × 109 can be reached at optimal conditions. Results have shown that single Ag@AuNWs can be utilized as a good platform for SERS applications with high sensitivity, stability, and reproducibility, which will benefit SERS-based research at the single entity level.

Stochastic Collision Electrochemistry from Single G-Quadruplex/Hemin: Electrochemical Amplification and MicroRNA Sensing.

Stochastic collision electrochemistry is a hot topic in single molecule/particle research, which provides an opportunity to investigate the details of the single molecule/particle reaction mechanism that is always masked in ensemble-averaged measurements. In this work, we develop an electrochemical amplification strategy to monitor the electrocatalytic behavior of single G-quadruplex/hemin (GQH) for the reaction between hydrogen peroxide and hydroquinone (HQ) through the collision upon a gold nanoelectrode. The intrinsic peroxidase activities of single GQH were investigated by stochastic collision electrochemical measurements, giving further insights into understanding biocatalytic processes. Based on the unique catalytic activity of GQH, we have also designed a hybridization chain reaction strategy to detect miRNA-15 with good selectivity and sensitivity. This work provided a meaningful strategy to investigate the electrochemical amplification and the broad application for nucleic acid sensing at the single molecule/particle level.

Enzyme-Encapsulated Zeolitic Imidazolate Frameworks Formed Inside the Single Glass Nanopore: Catalytic Performance and Sensing Application.

Metal-organic frameworks (MOFs) can improve the stability and activity of enzymes under the MOF encapsulation. However, it remains a challenge to explore the effects of the MOF environment on enzymatic activity in a confined space. In this work, we immobilized the enzyme inside a glass nanopore to study the catalytic activity and stability of the enzyme in the MOF environment. Horseradish peroxidase (HRP) is encapsulated in zeolitic imidazolate framework-90 (ZIF-90) and zeolitic imidazolate framework-8 (ZIF-8), which are used as the catalytic platforms. The HRP can catalyze 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS) molecules to generate ABTS+ ions, and the change of the transmembrane ion current will be monitored in real time. As the concentration of H2O2 increases, the amount of produced ABTS+ will increase; thus, the ionic current increases. The effects of the MOF structure on enzyme activity and stability are also investigated. The HRP encapsulated in the MOF and modified inside the nanopore provides a novel and unlabeled design for studying enzymatic catalysis in a confined environment, which should have extensive applications in chemical-/bio-sensing, electrocatalysis, and fundamental electrochemistry.

N-Type Quinoidal Polymers Based on Dipyrrolopyrazinedione for Application in All-Polymer Solar Cells.

Conjugated molecules and polymers with intrinsic quinoidal structure are promising n-type organic semiconductors, which have been reported for application in field-effect transistors and thermoelectric devices. In principle, the molecular and electronic characteristics of quinoidal polymers can also enable their application in organic solar cells. Herein, two quinoidal polymers, named PzDP-T and PzDP-ffT, based on dipyrrolopyrazinedione were synthesized and used as electron acceptors in all-polymer solar cells (all-PSCs). Both PzDP-T and PzDP-ffT showed suitable energy levels and wide light absorption range that extended to the near-infrared region. When combined with the polymer donor PBDB-T, the resulting all-PSCs based on PzDP-T and PzDP-ffT exhibited a power conversion efficiency (PCE) of 1.33 and 2.37 %, respectively. This is the first report on the application of intrinsic quinoidal conjugated polymers in all-PSCs. The photovoltaic performance of the all-PSCs was revealed to be mainly limited by the relatively poor and imbalanced charge transport, considerable charge recombination. Detailed investigations on the structure-performance relationship suggested that synergistic optimization of light absorption, energy levels, and charge transport properties is needed to achieve more successful application of intrinsic quinoidal conjugated polymers in all-PSCs.

A Facile Synthesized Polymer Featuring B-N Covalent Bond and Small Singlet-Triplet Gap for High-Performance Organic Solar Cells.

High-efficiency organic solar cells (OSCs) largely rely on polymer donors. Herein, we report a new building block BNT and a relevant polymer PBNT-BDD featuring B-N covalent bond for application in OSCs. The BNT unit is synthesized in only 3 steps, leading to the facile synthesis of PBNT-BDD. When blended with a nonfullerene acceptor Y6-BO, PBNT-BDD afforded a power conversion efficiency (PCE) of 16.1 % in an OSC, comparable to the benzo[1,2-b:4,5-b']dithiophene (BDT)-based counterpart. The nonradiative recombination energy loss of 0.19 eV was afforded by PBNT-BDD. PBNT-BDD also exhibited weak crystallinity and appropriate miscibility with Y6-BO, benefitting of morphological stability. The singlet-triplet gap (ΔEST ) of PBNT-BDD is as low as 0.15 eV, which is much lower than those of common organic semiconductors (≥0.6 eV). As a result, the triplet state of PBNT-BDD is higher than the charge transfer (CT) state, which would suppress the recombination via triplet state effectively.

Nanopore-based Strategy for Selective Detection of Single Carcinoembryonic Antigen (CEA) Molecules.

Nanopores have become one of the most important tools for single-molecule sensing, but the challenge for selective detection of specific biomolecules still exists. In this contribution, we develop a new technique for sensing carcinoembryonic antigen (CEA), one of the important cancer biomarkers, using solid-state nanopores as a tool. The method is based on the specific affinity between aptamer (Apt) modified magnetic Fe3O4-Au nanoparticles (MNPs) and CEA, and the formed CEA-Apt-MNPs and remaining Apt-MNPs can transport the nanopores by applying a positive potential after magnetic separation. Due to the obvious particle size difference between CEA-Apt-MNPs and Apt-MPs, their corresponding blockage signals could be distinguished completely by the degree of the current decline. Moreover, the frequency of the blockage signals for CEA-Apt-MNPs is proportional to the concentration of CEA within certain limits, indicating that our designed nanopore sensing strategy can quantitatively detect CEA in complex samples. This work demonstrates that our designed nanopore-based strategy can be used for CEA sensing with good selectivity and sensitivity and also can be used to analyze other protein biomarkers for early diagnosis and monitoring of cancer, though the detection limit (0.6 ng/mL) is not relatively low. In future works, we plan to improve our detection limit by the improvement of the nanopipette preparation technology and detection method.

Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes.

INTRODUCTION: This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). MATERIALS: A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1yr=2.62, 95%CI: 1.76-3.90; OR3yr=3.14, 95%CI: 2.33-4.24; OR5yr=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR1yr=2.52, 95%CI: 1.84-3.44; OR3yr=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR5yr=2.26, 95%CI: 0.94-5.45, P=0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2>50%). CONCLUSIONS: Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.

Unique Voltammetry of Silver Nanoparticles: From Single Particle to Aggregates.

Understanding the electrooxidation process of metal nanoparticles (NPs) is very important because they have showed wide applications in electrocatalysis, sensing, and nanoelectronics. In this letter, we designed a strategy to investigate the anodic stripping voltammetry (ASV) of silver oxidation at single NP level and aggregation state by using gold single nanoelectrodes (SNEs) and ultramicroelectrodes. Results showed that the ASV peak potential and shape were significantly affected by the diameter and aggregation degree of the Ag NPs: symmetrical-peak shape, two-peak shape, and asymmetrical-peak shape appeared when Ag NPs changed from the single particle state to the large-aggregation state, and size-dependent ASVs for Ag NPs oxidation were also observed. These findings can help us deeply understand the metal NPs oxidation process and will benefit the related applications.

Single Ag Nanowire Electrodes and Single Pt@Ag Nanowire Electrodes: Fabrication, Electrocatalysis, and Surface-Enhanced Raman Scattering Applications.

Silver nanowires (AgNWs) have received much attention due to their excellent optical, electrical, and conductive properties. In this work, we provided a new perspective for investigating the property of AgNWs from a single nanowire level. Single Ag nanowire electrodes and single Pt@Ag nanowire electrodes were fabricated by a laser-assisted pulling technique and galvanic replacement reaction (GRR). The radius, length, and metal ratio of the nanowires are tunable as needed. The prepared nanowire exhibited excellent electrocatalytic activity toward the methanol electro-oxidation and high sensitivity for monitoring the reduction of 4-nitrothiophenol by recording SERS spectra. This work will help us deeply understand the catalytic performance at the single nanowire level and open a new perspective for nanomaterials research.