A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Aggregation-Enabled Electrochemistry in Confined Nanopore Capable of Complementary Faradaic and Non-Faradaic Detection.

Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.

Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection.

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

Single-Cell Caspase-3 Measurement Using a Biomimetic Nanochannel.

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.

Highly Light-Harvesting MOF-on-MOF Heterostructure: Cascading Functionality to Flexible Photogating of Organic Photoelectrochemical Transistor and Bienzyme Cascade Detection.

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.

Photoresponsive Hydrogen-Bonded Organic Frameworks-Enabled Organic Photoelectrochemical Transistors for Sensitive Bioanalysis.

A facile route for exponential magnification of transconductance (gm) in an organic photoelectrochemical transistor (OPECT) is still lacking. Herein, photoresponsive hydrogen-bonded organic frameworks (PR-HOFs) have been shown to be efficient for gm magnification in a typical poly(ethylene dioxythiophene):poly(styrenesulfonate) OPECT. Specifically, 450 nm light stimulation of 1,3,6,8-tetrakis (p-benzoic acid) pyrene (H4TBAPy)-based HOF could efficiently modulate the device characteristics, leading to the considerable gm magnification over 78 times from 0.114 to 8.96 mS at zero Vg. In linkage with a DNA nanomachine-assisted steric hindrance amplification strategy, the system was then interfaced with the microRNA-triggered structural DNA evolution toward the sensitive detection of a model target microRNA down to 0.1 fM. This study first reveals HOFs-enabled efficient gm magnification in organic electronics and its application for sensitive biomolecular detection.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

High-Precision Single-Cell microRNA Therapy by a Functional Nanopipette with Sensitive Photoelectrochemical Feedback.

This work proposes the concept of single-cell microRNA (miR) therapy and proof-of-concept by engineering a nanopipette for high-precision miR-21-targeted therapy in a single HeLa cell with sensitive photoelectrochemical (PEC) feedback. Targeting the representative oncogenic miR-21, the as-functionalized nanopipette permits direct intracellular drug administration with precisely controllable dosages, and the corresponding therapeutic effects can be sensitively transduced by a PEC sensing interface that selectively responds to the indicator level of cytosolic caspase-3. The experimental results reveal that injection of ca. 4.4 × 10-20 mol miR-21 inhibitor, i.e., 26488 copies, can cause the obvious therapeutic action in the targeted cell. This work features a solution to obtain the accurate knowledge of how a certain miR-drug with specific dosages treats the cells and thus provides an insight into futuristic high-precision clinical miR therapy using personalized medicine, provided that the prerequisite single-cell experiments are courses of personalized customization.

θ-Nanopipette for Single-Cell Resistive-Pulse Profiling of DNA Repair Proteins Accompanied by Drug Evaluation.

Single-cell analysis of the DNA repair protein is important but remains unachieved. Exploration of nanopipettte technologies in single-cell electroanalysis has recently seen rapid growth, while the θ-nanopipette represents an emerging technological frontier with its potential largely veiled. Here a θ-nanopipette is first applied for single-cell resistive-pulse sensing (RPS) of the important DNA repair protein O6-alkylguanine DNA alkyltransferase (hAGT). The removal of alkyl mutations by hAGT could restore the damaged aptamer linking with a structural DNA carrier, allowing the selective binding of the aptamer to thrombin with precisely matched size to produce distinct RPS signals when passing through the orifice. Kinetic analysis of hAGT repair was studied. Meanwhile, the device shows the simultaneous on-demand infusion of inhibitors to inactivate the hAGT activity, indicative of its potential in drug screening for enhanced chemotherapy. This work provides a new paradigm for θ-nanopipette-based single-cell RPS of a DNA repair protein accompanied by drug evaluation.

Effects of positive psychological interventions on positive and negative emotions in depressed individuals: a systematic review and meta-analysis.

BACKGROUND: Positive psychological interventions (PPIs) are known to be effective in alleviating depression. However, the effect of PPIs on positive and negative emotions in depressed participants is not unclear. AIMS: To systematically investigate the effects of PPIs on positive and negative emotions in depressed individuals. METHODS: 6 databases were searched for randomized controlled trials of PPIs in individuals with depressive disorders or depressive symptoms. Hedges' g value was computed using a random-effects model to determine effect sizes. RESULTS: 14 trials from 13 studies were included. Our meta-analysis showed that PPIs had significant but small effects on improving positive affect (g = 0.33, p = .02), life satisfaction (g = 0.26, p = .03), happiness (g = 0.62, p = .03) and depression (g = -0.32, p = .001), and negligible effects on improving well-being (g = 0.13, p = .24) and negative affect (g = -0.15, p = .31). Subgroup analyses of depression showed that PPIs have experienced benefits in improving depression in most subgroups. In addition, none of the subgroup analyses performed for outcomes other than depression found PPIs to be more effective than controls. CONCLUSION: PPIs can improve positive affect, life satisfaction, happiness and depression in depressed individuals, but further studies are needed to validate their effects on well-being, and negative affect.

Metallointercalated-DNA Nanotubes as Functional Light Antenna for Organic Photoelectrochemical Transistor Biosensor with Minimum Background.

Organic photoelectrochemical transistor (OPECT) biosensor with a removed background is desired but remains challenging. So far, scientists still lack a solution to this issue. The light-matter interplay is expected to achieve an advanced OPECT with unknown possibilities. Here, we address this challenge by tailoring a unique heterogeneous light antenna as the functional gating module and its cascade interaction with a proper channel, which is exemplified by bioinduced [Ru(bpy)2dppz]2+-intercalated DNA nanotubes (NTs)/NiO heterojunction and its modulation against a diethylenetriamine-treated poly(ethylene dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel. Light stimulation of the antenna can generate the obvious cathodic photocurrent and, hence, modulate the channel, accomplishing OPECT with a minimal background and the hitherto highest current gain of 19 000. Linking with nucleic acid hybridization using microRNA-155 as the representative target, the device achieves sensitive biosensing down to 5.0 fM.

Hybridization Chain Reaction-Enhanced Biocatalytic Precipitation on Flower-like Bi2S3: Toward Organic Photoelectrochemical Transistor Aptasensing with High Transconductance.

Organic photoelectrochemical transistor (OPECT) bioanalysis has recently emerged as a promising avenue for biomolecular sensing, providing insight into the next-generation of photoelectrochemical biosensing and organic bioelectronics. Herein, this work validates the direct enzymatic biocatalytic precipitation (BCP) modulation on a flower-like Bi2S3 photosensitive gate for high-efficacy OPECT operation with high transconductance (gm), which is exemplified by a prostate-specific antigen (PSA)-dependent hybridization chain reaction (HCR) and subsequent alkaline phosphatase (ALP)-enabled BCP reaction toward PSA aptasensing. It has been shown that light illumination could ideally achieve the maximized gm at zero gate bias, and BCP could efficiently modulate the device's interfacial capacitance and charge-transfer resistance, resulting in a significantly changed channel current (IDS). The as-developed OPECT aptasensor realizes good analysis performance for PSA with a detection limit of 10 fg mL-1. This work features direct BCP modulation of organic transistors and is expected to stimulate further interest in exploring advanced BCP-interfaced bioelectronics with unknown possibilities.

Dual Functional Conjugated Acetylenic Polymers: High-Efficacy Modulation for Organic Photoelectrochemical Transistors and Structural Evolution for Bioelectronic Detection.

Conjugated acetylenic polymers (CAPs) have emerged as a unique class of metal-free semiconductors with tunable electrical and optical properties yet their full potential remains largely unexplored. Organic bioelectronics is envisioned to create more opportunities for innovative biomedical applications. Herein, we report a poly(1,4-diethynylbenzene) (pDEB)/NiO gated enhancement-mode poly(ethylene dioxythiophene)-poly(styrene sulfonate) organic photoelectrochemical transistor (OPECT) and its structural evolution toward bioelectronic detection. pDEB was synthesized via copper-mediated Glaser polycondensation of DEB monomers on the NiO/FTO substrate, and the as-synthesized pDEB/NiO/FTO can efficiently modulate the enhancement-mode device with a high current gain. Linking with a sandwich immunoassay, the labeled alkaline phosphatase can catalyze sodium thiophosphate to generate H2S, which will react with the diacetylene group in pDEB through the Michael addition reaction, resulting in an altered molecular structure and thus the transistor response. Exemplified by HIgG as the model target, the developed biosensor achieves highly sensitive detection with a linear range of 70 fg mL-1-10 ng mL-1 and a low detection limit of 28.5 fg mL-1. This work features the dual functional CAP-gated OPECT, providing not only a novel gating module but also a structurally new rationale for bioelectronic detection.

Biological Transformation of AgI on MOF-on-MOF-Derived Heterostructures: Toward Polarity-Switchable Photoelectrochemical Biosensors for Neuron-Specific Enolase.

The sensitive detection of neuron-specific enolase (NSE) as a biomarker for lung cancer at an early stage is critical but has long been a challenge. The emergence of polarity-switchable photoelectrochemical (PEC) bioanalysis has opened up new avenues for developing highly sensitive NSE sensors. In this study, we present such a biosensor depending on the bioinduced AgI transition on MOF-on-MOF-derived semiconductor heterojunctions. Specifically, treatment of ZnO@In2O3@AgI by bioproduced H2S can in situ generate the ZnO@In2O3@In2S3@Ag2S heterojunction, with the photocurrent switching from the cathodic to anodic one due to the changes in the carrier transfer pathway. Linking an NSE-targeted sandwich immunorecognition with labeled alkaline phosphatase (ALP) catalyzed generation of H2S, such a phenomenon was correlated to NSE concentration with good performance in terms of selectivity and sensitivity and a low detection limit of 0.58 pg/mL. This study offered a new perspective on the use of MOF-on-MOF-derived heterostructures for advanced polarity-switchable PEC bioanalysis.

Alkaline Phosphatase-Mediated Bioetching of CoOOH/BiVO4 for Signal-On Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) bioanalytics has recently appeared as a promising route for biological measurements, which has major implications in both next-generation photoelectrochemical (PEC) bioanalysis and futuristic biorelated implementations. Via biological dissociation of materials, bioetching is a useful technique for bio-manufacturing and bioanalysis. The intersection of these two domains is expected to be a possible way to achieve innovative OPECT bioanalytics. Herein, we validate such a possibility, which is exemplified by alkaline phosphatase (ALP)-mediated bioetching of a CoOOH/BiVO4 gate for a signal-on OPECT immunoassay of human immunoglobulin G (HIgG) as the model target. Specifically, target-dependent bioetching of the upper CoOOH layer could result into an enhanced electrolyte contact and light accessibility to BiVO4, leading to the modulated response of the polymeric poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel that could be monitored by the channel current. The introduced biosensor achieves sensitive detection of HIgG with high selectivity and sensitivity. This work features bioetching-enabled high-efficacy OPECT bioanalysis and is anticipated to serve as a generic protocol, considering the diverse bioetching routes.

Chemical Redox Cycling in an Organic Photoelectrochemical Transistor: Toward Dual Chemical and Electronic Amplification for Bioanalysis.

The organic photoelectrochemical transistor (OPECT) has been proven to be a promising platform to study the rich light-matter-bio interplay toward advanced biomolecular detection, yet current OPECT is highly restrained to its intrinsic electronic amplification. Herein, this work first combines chemical amplification with electronic amplification in OPECT for dual-amplified bioanalytics with high current gain, which is exemplified by human immunoglobulin G (HIgG)-dependent sandwich immunorecognition and subsequent alkaline phosphatase (ALP)-mediated chemical redox cycling (CRC) on a metal-organic framework (MOF)-derived BiVO4/WO3 gate. The target-dependent redox cycling of ascorbic acid (AA) acting as an effective electron donor could lead to an amplified modulation against the polymer channel, as indicated by the channel current. The as-developed bioanalysis could achieve sensitive HIgG detection with a good analytical performance. This work features the dual chemical and electronic amplification for OPECT bioanalysis and is expected to stimulate further interest in the design of CRC-assisted OPECT bioassays.

CuC(O) Interfaces Deliver Remarkable Selectivity and Stability for CO2 Reduction to C2+ Products at Industrial Current Density of 500 mA cm-2.

The electrocatalytic CO2 reduction reaction (CO2 RR) is an attractive technology for CO2 valorization and high-density electrical energy storage. Achieving a high selectivity to C2+ products, especially ethylene, during CO2 RR at high current densities (>500 mA cm-2 ) is a prized goal of current research, though remains technically very challenging. Herein, it is demonstrated that the surface and interfacial structures of Cu catalysts, and the solid-gas-liquid interfaces on gas-diffusion electrode (GDE) in CO2 reduction flow cells can be modulated to allow efficient CO2 RR to C2+ products. This approach uses the in situ electrochemical reduction of a CuO nanosheet/graphene oxide dots (CuOC(O)) hybrid. Owing to abundant CuOC interfaces in the CuOC(O) hybrid, the CuO nanosheets are topologically and selectively transformed into metallic Cu nanosheets exposing Cu(100) facets, Cu(110) facets, Cu[n(100) × (110)] step sites, and Cu+ /Cu0 interfaces during the electroreduction step, the faradaic efficiencie (FE) to C2+ hydrocarbons was reached as high as 77.4% (FEethylene  ≈ 60%) at 500 mA cm-2 . In situ infrared spectroscopy and DFT simulations demonstrate that abundant Cu+ species and Cu0 /Cu+ interfaces in the reduced CuOC(O) catalyst improve the adsorption and surface coverage of *CO on the Cu catalyst, thus facilitating CC coupling reactions.

Translation, cross-cultural adaptation, and psychometric investigation of Chinese version of the Orbach & Mikulincer Mental Pain Scale in patients with depressive disorder.

PURPOSE: This study aimed to translate, cross-culturally adapt, and preliminarily test the psychometric properties of the Chinese version of the Orbach & Mikulincer Mental Pain Scale (OMMP). METHODS: Psychometric investigation was performed on 240 depressed patients. The reliability of the Chinese version of the OMMP scale was expressed by internal consistency reliability and test-retest reliability (2-week interval), and confirmatory factor analysis (CFA) on the 8-factor, 31-item OMMP was conducted to examine the construct validity. RESULTS: The CFA showed that the modified model with 31 items had good reliability (Cronbach's α range = 0.691-0.871; ICC = 0.818). Criterion-related validity was also supported by significant and positive correlations between the eight factors and worst-ever suicidal ideation as well as depressive symptoms. CONCLUSION: The results indicated the usefulness of the OMMP-31 for Chinese depressed patients. It is necessary to estimate psychological pain to improve suicide management in the clinical setting.

A randomized controlled trial of a nurse-led psychological pain solution-focused intervention for depressed inpatients: study protocol.

BACKGROUND: Depressed patients commonly experience psychological pain. Research pointed to positive psychological interventions as an effective means of ameliorating psychological pain, although the exact effect is unclear. Based on the hope theory and solution-focused brief therapy (SFBT), this study combines hope theory with solution-focused brief therapy to develop a nurse-led psychological pain solution-focused (PPSF) intervention in depressed patients. METHODS: This is an assessor-blinded randomized controlled trial following the SPIRIT guidance. A total of 84 depressed patients will be recruited from the inpatient wards of a psychiatric hospital and randomly assigned to the control and experimental groups. Patients in the control group will be treated as usual. In contrast, patients in the experimental group will receive 6 sessions of the PPSF intervention for two weeks on top of the routine care. Primary outcomes are psychological pain, hope, cognitive distortions. Secondary outcomes are depression and suicidal ideation. Data will be collected at 5-time points: baseline, 1 and 2 weeks (post-intervention), 1 month (follow up), and 6 months after baseline. Generalized equation evaluation will be used to assess the effectiveness of the PPSF intervention. DISCUSSION: From a positive psychology perspective, there remains much room for developing psychological pain interventions in depressed patients. SFBT and hope theory are both based on positive psychology. With hope theory as the general framework and SFBT questions as the practical guide, the PPSF intervention program is designed that nursing staff can implement. If the intervention is effective, it will advance the development of psychological pain interventions for patients with depression. TRIAL REGISTRATION: ChiCTR2100048223.