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.

Metal-Organic Framework Nanofluidic Synapse.

Chemical synapse completes the signaling through neurotransmitter-mediated ion flux, the emulation of which has been a long-standing obstacle in neuromorphic exploration. Here, we report metal-organic framework (MOF) nanofluidic synapses in which conjugated MOFs with abundant ionic storage sites underlie the ionic hysteresis and simultaneously serve as catalase mimetics that sensitively respond to neurotransmitter glutamate (Glu). Various neurosynaptic patterns with adaptable weights are realized via Glu-mediated chemical/ionic coupling. In particular, nonlinear Hebbian and anti-Hebbian learning in millisecond time ranges are achieved, akin to those of chemical synapses. Reversible biochemical in-memory encoding via enzymatic Glu clearance is also accomplished. Such results are prerequisites for highly bionic electrolytic computers.

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.

Circadian Rhythm Disturbance in Acute Ischemic Stroke Patients and Its Effect on Prognosis.

INTRODUCTION: Poststroke sleep disturbances are common and can affect stroke outcomes, but the clinical studies mainly focus on breathing-related sleep disorders, while the bidirectional impact of circadian rhythm dysfunction in ischemic stroke remains unknown. This study observed the characteristics of melatonin secretion in acute ischemic stroke patients and evaluated whether melatonin rhythm impacts the prognosis after stroke by assessing the neurological function, cognition, emotion, and quality of life 3 months after stroke. METHODS: Acute ischemic stroke patients were selected from the Department of Neurology Inpatients of the Second Hospital affiliated with Soochow University from October 2019 to July 2021. Healthy control subjects were recruited at the same time. Demographic and clinical data were collected, and relevant scale scores (including neurological function, cognition, emotion, and sleep) were assessed within 2 weeks of onset and followed up 3 months later. All participants collected salivary melatonin samples on the 4th day of hospitalization and dim light melatonin onset (DLMO) was calculated according to melatonin concentration. Stroke patients were then divided into three groups based on their DLMO values. RESULTS: A total of 74 stroke patients and 33 control subjects were included in this analysis. Compared with healthy controls, stroke patients exhibited a delayed melatonin rhythm during the acute phase of stroke (21:36 vs. 20:38, p = 0.004). Stroke patients were then divided into three groups, namely normal (n = 36), delayed (n = 28), or advanced DLMO (n = 10), based on their DLMO values. A χ2 test showed that there were significant differences in the rate of poor prognosis (p = 0.011) and depression tendency (p = 0.028) among the three groups. A further pairwise comparison revealed that stroke patients with delayed DLMO were more likely to experience poor short-term outcomes than normal DLMO group (p = 0.003). The average melatonin concentration of stroke patients at 5 time points was significantly lower than that of the control group (3.145 vs. 7.065 pg/mL, p < 0.001). Accordingly, we split stroke patients into three groups, namely low melatonin level (n = 14), normal melatonin level (n = 54), or high melatonin level (n = 6). Unfortunately, there were no great differences in the clinical characteristics, cognition, emotion, sleep quality, and short-term outcome among groups. CONCLUSIONS: This is a preliminary study, and our results indicate that changes in melatonin secretion phase of stroke patients may have effect on their short-term prognosis.

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.

Electrochemical Single-Cell Protein Therapeutics Using a Double-Barrel Nanopipette.

Single-cell protein therapeutics is expected to promote our in-depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single-cell nanotools. We address this challenge by the use of a double-barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ-1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC-12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single-cell protein therapeutics provides a perspective for future single-cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids.

An Integrated Dual-Functional Nanotool Capable of Studying Single-Cell Epigenetics and Programmable Gene Regulation.

Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m6 A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6 A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6 A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation.

Importance of the ligand-to-metal charge transfer (LMCT) pathway in the photocatalytic oxidation of arsenite by TiO2.

Photooxidation of As(III) by TiO2 is a complicated process in which the oxidation mechanisms are always controversial. In this study, the enhanced photooxidation rates of As(III) with increasing pH values from 8.0 to 11.0 indicate the high photocatalytic reactivity of TiO2 under alkaline conditions. Moreover, As(III) improves the production of H2O2, indicating H-abstraction from As(III) (soluble or adsorbed) for H2O2 production. Although O2˙-, h+, ˙OH and -OOH are always regarded as the reactive oxygen species in the UV-TiO2 system, the superoxo and peroxo species formed on the surface of TiO2 also contribute to As(III) oxidation. The As(III)-O-Ti(IV) surface complexes formed on TiO2, as well as the decreased bandgaps of TiO2 with increasing concentrations of As(III) indicate that the ligand-to-metal charge transfer (LMCT) pathway also contributes to the oxidation of As(III) under alkaline conditions. Electrochemical analyses further reveal that As(III) enhances the electron density on the surface of TiO2, thereby improving the catalytic reactivity of TiO2. We therefore suggest that H-abstraction from As(III) or H2O to the formed superoxo and peroxo species results in the formation of H2O2, accompanied by the oxidation of As(III). This enriches our knowledge on the oxidation of As(III), as well as other contaminants rich in -OH groups during the photocatalytic oxidation processes.

Photocatalytic oxidation of Mn(II) on the surface of Bi2.15WO6via the ligand-to-metal charge transfer (LMCT) pathway.

Biotic and abiotic oxidation of Mn(II) in aqueous environments is an important process for the cycling of many elements. However, the mechanism involved in photocatalytic oxidation of Mn(II) has not been clearly elucidated yet. In this study, the photocatalytic oxidation of Mn(II) on the surface of self-doped Bi2+xWO6 (Bi2.15WO6) under visible light was conducted. Kinetics results show that visible light apparently accelerates the oxidation of Mn(II) to Mn(III, IV) oxides on Bi2.15WO6. The average oxidation states (AOS) of manganese reach 2.18 after 80 min of reaction under visible light at pH 8.50. Characterizations indicate the formation of Bi(III)-O-Mn(II) surface complexes between Mn(II) and surface Bi(III) on Bi2.15WO6, which then decreases the bandgap of [Bi2.15WO6 + Mn(II)]light (2.53 eV) compared with those of [Bi2.15WO6 + Mn(II)]dark (2.72 eV) and pure Bi2.15WO6 (2.86 eV), suggesting the contribution of the ligand-to-metal charge transfer (LMCT) pathway to the photocatalytic oxidation of Mn(II). Moreover, the addition of inorganic oxidants with strong oxidizing capacities (such as Cr2O72-, NO3- or NO2-) significantly increases the oxidation rate of Mn(II), further verifying the contribution of the LMCT pathway to Mn(II) oxidation. We therefore suggest that the LMCT pathway is one of the important oxidation routes for Mn(II) oxidation on Bi2.15WO6 under visible light.

A Photoelectrochemical Nanoreactor for Single-Cell Sampling and Near Zero-Background Faradaic Detection of Intracellular microRNA.

Rational utilization of the rich light-bio-matter interplay taking place in single-cell analysis represents a new technological direction in the field. The light-fueled operation is expected to achieve advanced photoelectrochemical (PEC) single-cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single-cell sampling and near zero-background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target-triggered hybridization chain reaction for binding the metallointercalator of [Ru(bpy)2 (dppz)]2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero-biased and near zero-background PEC method toward Faradaic detection of non-electrogenic miR at the single-cell level. Using this nanotool, lower miR concentration in the near-nucleus region than that in the main cytosol was revealed.

Twin Nanopipettes for Real-Time Electrochemical Monitoring of Cytoplasmic Microviscosity at a Single-Cell Level.

Cytoplasmic microviscosity (CPMV) plays essential roles in governing the diffusion-mediated cellular processes and has been recognized as a reliable indicator of the cellular response of many diseases and malfunctions. Current CPMV studies are exclusively established by probe-assisted optical methods, which nevertheless necessitate the complicated synthesis and delivery of optical probes into cells and thus the issues of biocompatibility and bio-orthogonality. Using twin nanopipettes integrated with a patch-clamp system, a practical electrochemical single-cell measurement is presented, which is capable of real-time and long-term CPMV detection without cell disruption. Specifically, upon the operation of the twin nanopipettes, the cellular CPMV status, which is correlated to cytoplasmic ionic mobility, could be sensibly transduced via the ionic current passing through the nanosystem. The average CPMV value of HeLa cells was detected as ca. 86 cP. Notably, the correlation between chemotherapy and CPMV alterations makes this approach possible for the real-time and long-term assessment of the evolution of external stimuli, as exemplified by the two natural products taxol and colchicine. Integrated with the patch-clamp setup, this study features the first use of twin nanopipettes for electrochemical CPMV monitoring of single living cells, and it is expected to inspire more interest in the exploitation of dual- and multiple nanopipettes for advanced single-cell analysis.

A Practical Electrochemical Nanotool for Facile Quantification of Amino Acids in Single Cell.

Though significant advances are made in the arena of single-cell electroanalysis, quantification of intracellular amino acids of human cells remains unsolved. Exemplified by l-histidine (l-His), this issue is addressed by a practical electrochemical nanotool synergizing the highly accessible nanopipette with commercially available synthetic DNAzyme. The fabricated nanotools are screened before operation of a single-use manner, and the l-His-provoked cleavage of the DNA molecules can be sensibly transduced by the ionic current rectification response, the intrinsic property of nanopipette governed by its interior surface charges. Regional distribution of cytosolic l-His level in human cells is electrochemically quantified for the first time, and time-dependent drug treatment effects are further revealed. This work unveils the possibility of electrochemistry for quantification of cytosolic amino acids of a spatial- and time-based manner and ultimately enables a better understanding of amino acid-involved events in living cells.

Observation of Acoustic Skyrmions.

Despite a long history of studies, acoustic waves are generally regarded as spinless scalar waves, until recent research revealed their rich structures. Here, we report the experimental observation of skyrmion configurations in acoustic waves. We find that surface acoustic waves trapped by a designed hexagonal acoustic metasurface give rise to skyrmion lattice patterns in the dynamic acoustic velocity fields (i.e., the oscillating acoustic air flows). Using an acoustic velocity sensing technique, we directly visualize a Néel-type skyrmion configuration of the acoustic velocity fields. We further demonstrate, respectively, the controllability and robustness of the acoustic skyrmion lattices by tuning the phase differences between the acoustic sources and by introducing local perturbations in our setup. Our study unveils a fundamental acoustic phenomenon that may enable unprecedented manipulation of acoustic waves and may inspire future technologies including advanced acoustic tweezers for the control of small particles.

An Integrated Photoelectrochemical Nanotool for Intracellular Drug Delivery and Evaluation of Treatment Effect.

With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single-cell study. Nevertheless, the present palette of single-cell tools lacks such a PEC-oriented solution. Here a dual-functional photocathodic single-cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target-specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p-type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single-cell nanotool and extended the boundary of current single-cell electroanalysis.

Liposome-Mediated in Situ Formation of AgI/Ag/BiOI Z-Scheme Heterojunction on Foamed Nickel Electrode: A Proof-of-Concept Study for Cathodic Liposomal Photoelectrochemical Bioanalysis.

This work reports the liposome-mediated in situ formation of the AgI/Ag/BiOI Z-scheme heterojunction on foamed nickel electrode for signal-on cathodic photoelectrochemical (PEC) bioanalysis. Specifically, in a proof-of-concept study, Ag nanoparticle-encapsulated liposomes were initially confined via the sandwich immunobinding and then processed to release numerous Ag+ ions, which were then directed to react with the BiOI/Ni electrode, resulting in the in situ generation of a AgI/Ag/BiOI Z-scheme heterojunction on the electrode. The enhanced cathodic signal could be correlated to the target concentration, which thus underlays a novel signal-on cathodic liposomal PEC bioanalysis strategy. Different from previous anodic liposomal PEC bioanalysis, this work features the first cathodic liposomal PEC bioanalysis on the basis of the in situ formation of a Z-scheme heterojunction. More generally, integrated with various biorecognition events, this protocol could serve as a common basis for addressing numerous targets of interest.

Hybrid Acoustic Topological Insulator in Three Dimensions.

Topological insulators (TIs), featured by a symmetry-protected gapless surface Dirac cone(s) in their complete energy band gaps, have been extended from condensed-matter physics to classical bosonic systems in the last decade. However, acoustic TIs in three dimensions remain elusive because of a lack of a spin or polarization degree of freedom for longitudinal airborne sound. Here, we experimentally demonstrate a feasible way to hybridize an acoustic TI in three dimensions based on band inversion through a three-dimensional (3D) hybrid Dirac point (HDP). Such a 3D HDP, with linear dispersion in the layer plane while quadratic out of the layer, is distinct from a general point with linear dispersion in all directions. Interestingly, a single nearly gapless conical-like dispersion for acoustic surface states can be achieved at both zigzag and armchair interfaces, supporting robust sound transport. Our findings can serve as a tabletop platform for exploring unique acoustic applications based on the two-dimensional topological interfaces.

Surface phononic graphene.

Strategic manipulation of wave and particle transport in various media is the key driving force for modern information processing and communication. In a strongly scattering medium, waves and particles exhibit versatile transport characteristics such as localization, tunnelling with exponential decay, ballistic, and diffusion behaviours due to dynamical multiple scattering from strong scatters or impurities. Recent investigations of graphene have offered a unique approach, from a quantum point of view, to design the dispersion of electrons on demand, enabling relativistic massless Dirac quasiparticles, and thus inducing low-loss transport either ballistically or diffusively. Here, we report an experimental demonstration of an artificial phononic graphene tailored for surface phonons on a LiNbO3 integrated platform. The system exhibits Dirac quasiparticle-like transport, that is, pseudo-diffusion at the Dirac point, which gives rise to a thickness-independent temporal beating for transmitted pulses, an analogue of Zitterbewegung effects. The demonstrated fully integrated artificial phononic graphene platform here constitutes a step towards on-chip quantum simulators of graphene and unique monolithic electro-acoustic integrated circuits.

Precise characterization of self-catalyzed III-V nanowire heterostructures via optical second harmonic generation.

We demonstrate the utility of optical second harmonic generation (SHG) polarimetry to perform structural characterization of self-assembled zinc-blende/wurtzite III-V nanowire heterostructures. By analyzing four anisotropic SHG polarimetric patterns, we distinguish between wurtzite (WZ), zinc-blende (ZB) and ZB/WZ mixing III-V semiconducting crystal structures in nanowire systems. By neglecting the surface contributions and treating the bulk crystal within the quasi-static approximation, we can well explain the optical SHG polarimetry from the NWs with diameter from 200-600 nm. We show that the optical in-coupling and out-coupling coefficients arising from depolarization field can determine the polarization of the SHG. We also demonstrate micro-photoluminescence of GaAs quantum dots in related ZB and ZB/WZ mixing sections of core-shell NW structure, in agreement with the SHG polarimetry results. The ability to perform in situ SHG-based crystallographic study of semiconducting single and multi-crystalline nanowire heterostructures will be useful in displaying structure-property relationships of nanodevices.

Lower Melatonin Indicates Poor Short-term Prognosis in Patients with Acute Ischemic Stroke.

AIMS: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored the impact of possible changes in melatonin levels on the prognosis of patients. METHODS: This study recruited acute ischemic stroke (AIS) patients from the Department of the Second Affiliated Hospital of Soochow University between December 2019 and June 2021, along with healthy control subjects. Salivary melatonin samples were collected from each participant between 7 pm and 10 pm, and fasting plasma was collected the following morning to measure the levels of inflammatory markers. The prognosis was assessed through follow-up three months after discharge. The relationship between melatonin levels and plasma inflammatory markers was assessed, followed by an analysis of the effect of melatonin levels on patient prognosis. RESULTS: The study enrolled a total of 160 participants, including 120 AIS patients aged 50 years or older (61.7% male) and 40 age-matched controls (55.0% male). The AIS group exhibited lower salivary melatonin levels at 19 (P = 0.002), 20 (P < 0.001), 21 (P < 0.001), and 22 (P < 0.001) o'clock, and the average melatonin level was also lower (P < 0.001). Logistic regression analysis models indicated an association between low melatonin levels and poor prognosis. Salivary melatonin levels demonstrated good predictive ability for the prognosis of AIS patients. CONCLUSION: Melatonin levels were lower in AIS patients compared to controls. In addition, lower melatonin levels were associated with a poorer prognosis among AIS patients.

Monolithic Strong Coupling of Topological Surface Acoustic Wave Resonators on Lithium Niobate.

Coherent phonon transfer via high-quality factor (Q) mechanical resonator strong coupling has garnered significant interest. Yet, the practical applications of these strongly coupled resonator devices are largely constrained by their vulnerability to fabrication defects. In this study, topological strong coupling of gigahertz frequency surface acoustic wave (SAW) resonators with lithium niobate is achieved. The nanoscale grooves are etched onto the lithium niobate surface to establish robust SAW topological interface states (TISs). By constructing phononic crystal (PnC) heterostructures, a strong coupling of two SAW TISs, achieving a maximum Rabi splitting of 22 MHz and frequency quality factor product fQm of ≈1.2 × 1013 Hz, is realized. This coupling can be tuned by adjusting geometric parameters and a distinct spectral anticrossing is experimentally observed. Furthermore, a dense wavelength division multiplexing device based on the coupling of multiple TISs is demonstrated. These findings open new avenues for the development of practical topological acoustic devices for on-chip sensing, filtering, phonon entanglement, and beyond.