An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning.

Octopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions, including olfactory associative learning. However, the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect it. To overcome these limitations, we developed a genetically encoded GPCR  activation-based (GRAB) OA sensor called GRABOA1.0. This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA. Using GRABOA1.0, we monitored OA release in the Drosophila mushroom body (MB), the fly's learning center, and found that OA is released in response to both odor and shock stimuli in an aversive learning model. This OA release requires acetylcholine (ACh) released from Kenyon cells, signaling via nicotinic ACh receptors. Finally, we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octß1R in dopaminergic neurons, leading to alterations in synaptic plasticity within the MB. Thus, our new GRABOA1.0 sensor can be used to monitor OA release in real time under physiological conditions, providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

Highly Sensitive Near-Field Electrochemical Sensor for In Vivo Monitoring of Respiratory Patterns.

Real-time tracking of respiratory patterns provides noninvasive and quick access for evaluating pathophysiological conditions yet remains challenging due to limited temporal resolution and poor sensitivity to dig out fingerprints of respiratory waveforms. Here, we report an electrochemical sensor for accurately tracing respiratory patterns of small animal models based on the electrochemical impedance mechanism for wireless coupling of a graphdiyne oxide (GYDO)-modified sensing coil chip and a reader coil chip via near-field magnetic induction. In the electrochemical impedance measurement mode, an alternating current is applied through the reader coil chip to perturb proton transport at the GYDO interface of the sensing coil chip. As demonstrated, a high-frequency perturbing condition significantly reduces the interfacial resistance for proton transport by 5 orders of magnitude under 95% relative humidity (RH) and improves the low-humidity responses with a limit of detection down to 0.2% RH, enabling in vivo accurate profiling of respiratory patterns on epileptic rats. The electrochemical impedance coupling system holds great potential for new wireless bioelectronics.

Aptamer-Based Potentiometric Sensor Enables Highly Selective and Neurocompatible Neurochemical Sensing in Rat Brain.

Selective and nondisruptive in vivo neurochemical monitoring within the central nervous system has long been a challenging endeavor. We introduce a new sensing approach that integrates neurocompatible galvanic redox potentiometry (GRP) with customizable phosphorothioate aptamers to specifically probe dopamine (DA) dynamics in live rat brains. The aptamer-functionalized GRP (aptGRP) sensor demonstrates nanomolar sensitivity and over a 10-fold selectivity for DA, even amidst physiological levels of major interfering species. Notably, conventional sensors without the aptamer modification exhibit negligible reactivity to DA concentrations exceeding 20 µM. Critically, the aptGRP sensor operates without altering neuronal activity, thereby permitting real-time, concurrent recordings of both DA flux and electrical signaling in vivo. This breakthrough establishes aptGRP as a viable and promising framework for the development of high-fidelity sensors, offering novel insights into neurotransmission dynamics in a live setting.

An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning.

Octopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions, including olfactory associative learning. However, the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect it. To overcome these limitations, we developed a genetically encoded GPCR activation-based (GRAB) OA sensor called GRABOA1.0. This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA. Using GRABOA1.0, we monitored OA release in the Drosophila mushroom body (MB), the fly's learning center, and found that OA is released in response to both odor and shock stimuli in an aversive learning model. This OA release requires acetylcholine (ACh) released from Kenyon cells, signaling via nicotinic ACh receptors. Finally, we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octß1R in dopaminergic neurons, leading to alterations in synaptic plasticity within the MB. Thus, our new GRABOA1.0 sensor can be used to monitor OA release in real-time under physiological conditions, providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

Stabilization of cadmium in a fluvo-aquic soil-Chinese chive system using loess and chicken manure compost.

The stabilization of heavy metals in soil has been increasingly applied in China in recent years due to its quick effect and low cost. In this study, loess and chicken manure compost (a commercial organic fertilizer) were used to stabilize Cd in slightly polluted fluvo-aquic soil from the North China Plain, and the driving factors for stabilization were investigated through ridge regression. The additives significantly reduced the total concentration of Cd in soil through dilution. The addition of loess and compost increased carbonates and organic matter in soil, respectively. This caused exchangeable Cd to be transformed to fractions bound to carbonates or organic matter, thereby decreasing the concentration of Cd in the roots and leaves of Chinese chive. The decreasing exchangeable Cd in soil was the direct cause of decreased uptake of Cd by plants, and the increasing fractions bound to carbonates or organic matter were indirect influencing factors. However, adding loess decreased soil fertility and retarded plant growth. The addition of compost compensated for these defects. This study suggests that the combined addition of loess and chicken manure compost was able to effectively reduce the total concentration and phytoavailability of Cd in soil and guarantee crop yield and quality.

Dopamine Release Impairments Accompany Movement Vigor Deficiency in an Exercise-Induced Fatigue Mouse Model.

Fatigue is a common symptom in neurological diseases with a complex cause, involving the influence of events occurring in both the central and peripheral nervous systems. When people suffer from fatigue, a general decline in their movement performance typically occurs. The neural representation of dopamine signaling in the striatum plays a crucial role in movement regulation. Movement vigor is regulated by dopamine-dependent neuron activity in the striatum. However, whether exercise-induced fatigue alters stimulated dopamine release and further affects movement vigor has not been described. Here, for the first time, we used fast-scan cyclic voltammetry to demonstrate the effect of exercise-induced fatigue on stimulated dopamine release in the striatum in combination with a fiber photometry system to observe the excitability of striatal neurons. The movement vigor of mice was reduced, and after fatigue, the balance of excitability of striatal neurons regulated by dopamine projections was disturbed, which was induced by a reduction in dopamine release. Additionally, D2DR regulation may serve as a targeted intervention to alleviate exercise-induced fatigue and promote fatigue recovery.

Molecular unravelling of the mechanism of overpotential change at the carbon nanotubes-modified gold electrode surface.

Using liquid secondary ion mass spectrometry, we in situ unraveled that the single walled carbon nanotubes-modified gold electrode surface is free of a dense adsorption phase and abundant in water molecules, which facilitated the electro-oxidation reaction of ascorbate. Such an understanding will expedite the knowledge-based development of electrochemical interfaces.

Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: a pharmacovigilance disproportionality analysis.

Introduction: existing research on children consists primarily of phase I/II clinical trials for VEGFR-TKI. System reports of safety on the use of VEGFR-TKI in pediatrics are lacking. Aim: to investigate the safety profiles of VEGFR-TKI in pediatrics via the FDA Adverse Event Reporting System (FAERS). Method: data regarding VEGFR-TKIs were extracted from the FAERS between 2004Q1 to 2022Q3 and categorized by the Medical Dictionary for Regulatory Activities (MedDRA). Population characteristics were analyzed, and reporting odds ratio (ROR) was performed to identify risk signals associated with VEGFR-TKI. Results: 53,921 cases containing 561 children were identified in the database from 18 May 2005, to 30 September 2022. Among those in the system organ class, skin, subcutaneous tissue disorders, and blood and lymphatic system disorders in pediatrics contributed to over 140 cases. Palmar-plantar eythrodysesthesia syndrome (PPES) in VEGFR-TKI presented the most significant 340.9 (95% 229.2-507.0). And pneumothorax also gave a high reporting odds ratio of 48.9 (95% 34.7-68.9). For a specific drug, musculoskeletal pain gave a ROR of 78.5 (95% 24.4-252.6) in cabozantinib and oesophagitis in lenvatinib with a ROR of 95.2 (95% 29.5-306.9). Additionally, hypothyroidism presented a high signal, especially sunitinib, with a ROR of 107.8 (95% 37.6-308.7). Conclusion: the present study explored the safety profile of VEGFR-TKI in pediatrics using the FAERS database. Multiple skin and subcutaneous tissue disorders, as well as blood and lymphatic system disorders, were common VEGFR-TKI-related AEs in system organ class. No serious hepatobiliary AEs were detected. For the specific AEs, PPES and pneumothorax were VEGFR-TKI-related AEs that presented significantly higher signals than those in the general population.

Stability Enhancement of Galvanic Redox Potentiometry by Optimizing the Redox Couple in Counterpart Poles.

Potentiometry based on the galvanic cell mechanism, i.e., galvanic redox potentiometry (GRP), has recently emerged as a new tool for in vivo neurochemical sensing with high neuronal compatibility and good sensing property. However, the stability of open circuit voltage (EOC) outputting remains to be further improved for in vivo sensing application. In this study, we find that the EOC stability could be enhanced by adjusting the sort and the concentration ratio of the redox couple in the counterpart pole (i.e., indicating electrode) of GRP. With dopamine (DA) as the sensing target, we construct a spontaneously powered single-electrode-based GRP sensor (GRP2.0) and investigate the correlation between the stability and the redox couple used in the counterpart pole. Theoretical consideration suggests that the EOC drift is minimum when the concentration ratio of the oxidized form (O1) to the reduced form (R1) of the redox species in the backfilled solution is 1:1. The experimental results demonstrate that, compared with other redox species (i.e., dissolved O2 at 3 M KCl, potassium ferricyanide (K3Fe(CN)6), and hexaammineruthenium(III) chloride (Ru(NH3)6Cl3)) used as the counterpart pole, potassium hexachloroiridate(IV) (K2IrCl6) exhibits better chemical stability and outputs more stable EOC. As a result, when IrCl62-/3- with the concentration ratio of 1:1 is used as the counterpart, GRP2.0 displays not only an excellent EOC stability (i.e., 3.8 mV drifting during 2200 s for in vivo recording) but also small electrode-to-electrode variation (i.e., the maximum EOC variation between four electrodes is 2.7 mV). Upon integration with the electrophysiology, GRP2.0 records a robust DA release, accompanied by a burst of neural firing, during the optical stimulation. This study paves a new avenue to stable neurochemical sensing in vivo.

Galvanic Redox Potentiometry for Fouling-Free and Stable Serotonin Sensing in a Living Animal Brain.

Serotonin (5-HT) is a major neurotransmitter broadly involved in many aspects of feeling and behavior. Although its electro-activity makes it a promising candidate for electrochemical sensing, the persistent generation of fouling layers on the electrode by its oxidation products presents a hurdle for reliable sensing. Here, we present a fouling-free 5-HT sensor based on galvanic redox potentiometry. The sensor efficiently minimizes electrode fouling as revealed by in situ Raman spectroscopy, ensuring a less than 3 % signal change in a 2 hour continuous experiment, whereas amperometric sensors losing 90 % within 30 min. Most importantly, the sensor is highly amenable for in vivo studies, permitting real-time 5-HT monitoring, and supporting the mechanism associated with serotonin release in brain. Our system offers an effective way for sensing different neurochemicals having significant fouling issues, thus facilitating the molecular-level understanding of brain function.

Deep Learning for Voltammetric Sensing in a Living Animal Brain.

Numerous neurochemicals have been implicated in the modulation of brain function, making them appealing analytes for sensors and diagnostics. However, it is a grand challenge to selectively measure multiple neurochemicals simultaneously in vivo because of their great variations in concentrations, dynamic nature, and composition. Herein, we present a deep learning-based voltammetric sensing platform for the highly selective and simultaneous analysis of three neurochemicals in a living animal brain. The system features a carbon fiber electrode capable of capturing the mixed dynamics of a neurotransmitter, neuromodulator, and ions. Then a powerful deep neural network is employed to resolve individual chemical and spatial-temporal information. With this, a single electrochemical measurement reveals an interplaying concentration changes of dopamine, ascorbate, and ions in living rat brain, which is unobtainable with existing analytical methodologies. Our strategy provides a powerful means to expedite research in neuroscience and empower sensing-aided diagnostic applications.

Hierarchical Self-assembly of Discrete Metal-Organic Cages into Supramolecular Nanoparticles for Intracellular Protein Delivery.

Hierarchical self-assembly (HAS) is a powerful approach to create supramolecular nanostructures for biomedical applications. This potency, however, is generally challenged by the difficulty of controlling the HAS of biomacromolecules and the functionality of resulted HAS nanostructures. Herein, we report a modular approach for controlling the HAS of discrete metal-organic cages (MOC) into supramolecular nanoparticles, and its potential for intracellular protein delivery and cell-fate specification. The hierarchical coordination-driven self-assembly of adamantane-functionalized M12 L24 MOC (Ada-MOC) and the host-guest interaction of Ada-MOC with ß-cyclodextrin-conjugated polyethylenimine (PEI-ßCD) afford supramolecular nanoparticles in a controllable manner. HAS maintains high efficiency and orthogonality in the presence of protein, enabling the encapsulation of protein into the nanoparticles for intracellular protein delivery for therapeutic application and CRISPR/Cas9 genome editing.

Single-Carbon-Fiber-Powered Microsensor for In Vivo Neurochemical Sensing with High Neuronal Compatibility.

The development of new principles and techniques with high neuronal compatibility for quantitatively monitoring the dynamics of neurochemicals is essential for deciphering brain chemistry and function but remains a great challenge. We herein report a neuron-compatible method for in vivo neurochemical sensing by powering a single carbon fiber through spontaneous bipolar electrochemistry as a new sensing platform. By using ascorbic acid as a model target to prove the concept, we found that the single-carbon-fiber-powered microsensor exhibited a good response, high stability and, more importantly, excellent neuronal compatibility. The microsensor was also highly compatible with electrophysiological recording, thus enabling the synchronous recording of both chemical and electrical signals. The sensing principle could be developed for in vivo monitoring of various neurochemicals in the future by rationally designing and tuning the electrochemical reactions at the two poles of the carbon fiber.

A Generalizable and Noncovalent Strategy for Interfacing Aptamers with a Microelectrode for the Selective Sensing of Neurotransmitters In†Vivo.

The selective sensing of neurochemicals is essential for understanding the chemical basis of brain function and pathology. Interfacing the excellent recognition features of aptamers with in vivo compatible carbon fiber microelectrode (CFE)-based electroanalytical systems offers a plausible means to achieve this end. However, this is challenging in terms of coupling chemistry, stability, and versatility. Here, we present a new interfacial functionalization strategy based on the assembly of aptamer cholesterol amphiphiles (aptCAs) on the alkyl chain-functionalized CFE. The noncovalent cholesterol-alkyl chain interactions effectively immobilize aptamers onto the CFE surface, allowing the generation of a highly selective system for probing neurochemical dynamics in living systems and opening up a vast array of new opportunities for designing in vivo sensors for exploring brain chemistry.

Graphdiyne oxide: a new carbon nanozyme.

Graphdiyne (GDY) is a new recently-synthesized carbon allotrope. We find here that graphdiyne oxide (GDYO), the oxidized form of GDY, can serve as a new kind of carbon nanozyme mimicking peroxidase. This finding essentially offers a new platform for fundamental understanding of carbon nanozymes and broadens the application of GDY.

Metal-Organic Framework Membrane Nanopores as Biomimetic Photoresponsive Ion Channels and Photodriven Ion Pumps.

Biological ion channels and ion pumps with sub-nanometer sizes modulate ion transport in response to external stimuli. Realizing such functions with sub-nanometer solid-state nanopores has been an important topic with wide practical applications. Herein, we demonstrate a biomimetic photoresponsive ion channel and photodriven ion pump using a porphyrin-based metal-organic framework membrane with pore sizes comparable to hydrated ions. We show that the molecular-size pores enable precise and robust optoelectronic ion transport modulation in a broad range of concentrations, unparalleled with conventional solid-state nanopores. Upon decoration with platinum nanoparticles to form a Schottky barrier photodiode, photovoltage across the membrane is generated with "uphill" ion transport from low concentration to high concentration. These results may spark applications in energy conversion, ion sieving, and artificial photosynthesis.

Optoelectronic modulation of ionic conductance and rectification through a heterogeneous 1D/2D nanofluidic membrane.

A smart mixed-dimensional heterogeneous membrane is fabricated, through which the ionic conductance and rectification can be precisely and robustly modulated by visible light of 420 nm wavelength with different power intensities simultaneously. The excellent performance makes it a promising alternative for further applications in nanoconfinement analysis.

Fluorine Doped Cagelike Carbon Electrocatalyst: An Insight into the Structure-Enhanced CO Selectivity for CO2 Reduction at High Overpotential.

The critical bottleneck of electrocatalytic CO2 reduction reaction (CO2RR) lies in its low efficiency at high overpotential caused by competitive hydrogen evolution. It is challenging to develop an efficient catalyst achieving both high current density and high Faradaic efficiency (FE) for CO2RR. Herein, we synthesized fluorine-doped cagelike porous carbon (F-CPC) by purposely tailoring its structural properties. The optimized F-CPC possesses large surface area with moderate mesopore and abundant micropores as well as high electrical conductivity. When used as catalyst for CO2RR, F-CPC exhibits FE of 88.3% for CO at -1.0 V vs RHE with a current density of 37.5 mA·cm -2. Experimental results and finite element simulations demonstrate that the excellent CO2RR performance of F-CPC at high overpotential should be attributed to its structure-enhanced electrocatalytic process stemming from its cagelike morphology.

Enhanced Electrosorption Ability of Carbon Nanocages as an Advanced Electrode Material for Capacitive Deionization.

The structure of an electrode material has an important impact on the performance of a capacitive deionization (CDI) device. However, it is still a challenge to design and synthesize electrode materials with a rational structure based on deep understanding of their structure-dependent CDI performance. Herein, we report the preparation of carbon nanocages (CNCs) with regulated shell thickness and a rich pore structure as an advanced material for high-performance CDI electrodes. The as-prepared CNC has a considerable specific capacitance of 149 F g-1 at a scan rate of 5 mV s-1. When used as CDI electrodes, the CNC shows an outstanding electrosorption ability of 17.5 mg g-1 at 1.4 V at an initial concentration of 250 mg L-1 NaCl solution. Furthermore, the CNC electrode displays high salt adsorption rate and good cyclic stability. Finite element simulations reveal that the superior structure of the CNC substantially promotes the ion transfer rate by shortening ion diffusion paths in the cavity of the electrode material. Also, both inner and outer walls of the CNC provide sufficient active sites for fast adsorption and desorption of salty ions. This work not only demonstrates that the CNC is a potential electrode material for CDI applications but also paves a way to design and prepare high-performance electrode materials based on a new perspective on their structure-performance relationship.

Water Adsorption and Transport on Oxidized Two-Dimensional Carbon Materials.

Studies on the adsorption and transport of water molecules with oxidized two-dimensional (2 D) carbon materials have attracted increasing interest owing to their wide range of applications, such as sensing, energy conversion, and membrane separation. In this contribution, the interaction between water molecules and oxidized 2 D carbon materials (i.e., graphene oxide and graphdiyne oxide) is discussed, the influence of water adsorption and transport on the physicochemical properties of 2 D carbon materials is presented, and the recent progress on oxidized 2 D carbon material-based proton conduction, electricity generation, water transport, and humidity sensing is highlighted. The opportunities and challenges in these research fields are discussed, especially the structural stability and chemical modification of 2 D carbon materials.