Ion Transport in Multi-Nanochannels Regulated by pH and Ion Concentration.

Nanochannels are a powerful technique for detecting a wide range of biomolecules without labeling. The ion transport phenomena in nanochannel arrays differ from those in single nanochannels and are caused by interchannel communication. This study uses a fully coupled Poisson-Nernst-Planck (PNP) and Navier-Stokes model to investigate ion transport in nanochannel arrays. Instead of being set at a constant value, the surface charge density used in this study is established by the protonation and deprotonation of the silanol groups that are present on the walls of the silicon-based nanochannels. The surface charge density of the nanochannel walls varies with the number of nanochannels, the channel lateral distance, and the background solution properties, which consequently influence the ionic concentration distribution, flow velocity, and electric field strength. For example, in different numbers of nanochannel systems, the ion concentration in nanochannels is not much different, but it is different in reservoirs, especially near the openings of nanochannels. The number of nanochannels and the distance between nanochannels can also affect the formation of electro-convective vortex zones under certain conditions. These findings can aid in optimizing the nanochannel array design by regulating the number and distance of nanochannels and facilitating the construction of solid-state nanochannel arrays with any desired nanochannel dimensions.

Controllable and Stable Fusion Strategy on Microfluidics.

This paper presents a microfluidic device with 200 cell "cage" structures. Based on this microfluidics device, a new simple and stable electrofusion method was developed. Under hydrodynamic force, the cells moved to the desired "cage" cell capture structure and efficiently formed cell pairs (∼80.0 ± 4.6%). Intimate intercellular connectivity was induced by the precise modulation of hypotonic solution substitution and the microstructure, which ensured no cell movement or displacement during the cell electroporation/electrofusion process. It also guaranteed repeated electroporation occurring in the same contact region and provided a stable cell membrane recombination and a cell fusion microenvironment. When the pulse signal was applied, a high fusion efficiency of ∼88.3 ± 0.6% was demonstrated on the microfluidic device.

Effect of Membrane Thickness on Ion Transport in pH-Regulated Zero-Depth Interfacial Nanopores.

Zero-depth interfacial nanopores, which are formed by two crossed nanoscale channels at their intersection interface, have been proposed to increase the spatial resolution of solid-state nanopores. However, research on zero-depth interfacial nanopores is still in its early stages. Although it has been shown that the current passing through an interfacial nanopore is largely independent of the membrane thickness, existing studies have not fully considered the impact of membrane thickness on other ion transport characteristics within these nanopores. In this paper, we investigate the electrokinetic ion transport phenomenon in the zero-depth interfacial nanopores, especially focusing on the influence of membrane thickness on the ion transport phenomenon. Our model incorporates the Poisson-Nernst-Planck equations and the Navier-Stokes equations, featuring a pH-regulated surface charge density. We find that when the thickness of the nanochannels is close to the interface size of the formed interfacial nanopore, the phenomenon of ion transport in the interfacial nanopore is similar to that in a conventional cylindrical nanopore. However, when the thickness of the nanochannels is much greater than the interface size of the formed interfacial nanopore, several distinct phenomena occur. The surface charge density on the inner walls of the interfacial nanopores has a small peak at the interface of the two crossing nanochannels, and the anion concentration changes greatly between the two nanochannels; that is, a much greater anion concentration forms in the nanochannel near the anode side than in the nanochannel near the cathode side. When the surface charge is nonzero, the electric field within the interfacial nanopore creates three extreme points, and the directions of the local electric fields are opposite at the ends of the membrane.

Advances of Strategies to Increase the Surface Charge Density of Triboelectric Nanogenerators: A Review.

Triboelectric nanogenerators (TENGs) have manifested a remarkable potential for harvesting environmental energy and have the prospects to be utilized for various uses, for instance, self-powered sensing devices, flexible wearables, and marine corrosion protection. However, the potential for further development of TENGs is restricted on account of their low output power that in turn is determined by their surface charge density. The current review majorly focuses on the selection and optimization of triboelectric materials. Subsequently, various methods capable of enhancing the surface charge density of TENGs, including environmental regulation, charge excitation, charge pumping, electrostatic breakdown, charge trapping, and liquid-solid structure are comprehensively reviewed. Lastly, the review is concluded by highlighting the existing challenges in enhancing the surface charge density of TENGs and exploring potential opportunities for future research endeavors in this area.

Laser patterned graphene pressure sensor with adjustable sensitivity in an ultrawide response range.

Flexible pressure sensors have attracted wide attention because of their applications in wearable electronic, human-computer interface, and healthcare. However, it is still a challenge to design a pressure sensor with adjustable sensitivity in an ultrawide response range to satisfy the requirements of different application scenarios. Here, a laser patterned graphene pressure sensor (LPGPS) is proposed with adjustable sensitivity in an ultrawide response range based on the pre-stretched kirigami structure. Due to the out-of-plane deformation of the pre-stretched kirigami structure, the sensitivity can be easily tuned by simply modifying the pre-stretched level. As a result, it exhibits a maximum sensitivity of 0.243 kPa-1, an ultrawide range up to 1600 kPa, a low detection limit (6 Pa), a short response time (42 ms), and excellent stability with high pressure of 1200 kPa over 500 cycles. Benefiting from its high sensitivity and ultrawide response range, the proposed sensor can be applied to detect physiological and kinematic signals under different pressure intensities. Additionally, taking advantage of laser programmable patterning, it can be easily configured into an array to determine the pressure distribution. Therefore, LPGPS with adjustable sensitivity in an ultrawide response range has potential application in wearable electronic devices.

A thematic content analysis of the structure and effects of good doctor abilities in China.

BACKGROUND: The efforts to explore and build the structure of good doctor abilities are important because they help improve the quality of education for medical students and better standardize the working performance of doctors. However, at present, no worldwide standards for such a structure have been established. In this study, we endeavoured to map the structure of good doctor abilities and identify their effects. METHODS: With a focus on China, a thematic content analysis was adopted in this study to analyse the personal profiles of 50 widely recognized good doctors. NVivo11 software was used. RESULTS: The Structure and Effects of Good Doctor Abilities in China model was proposed, and interpretations were made based on AMO theory. Good doctor abilities fall within six categories: rigorous clinical thinking, skilled in diagnosis and therapy, clinical empathy, continuous learning and innovation, enhancing and sharing experiences, and communication and coordination. These abilities have positive impacts on doctors' work performances and social benefits by encouraging good behaviours, ultimately promoting the sustainable development of the hospitals where they serve. CONCLUSIONS: In this study, we established a model of the structure and effects of good-doctor abilities in China and interpreted its mechanism, innovation and theory diversification in "good-doctor" research. Moreover, this study has practical significance because it provides systematic and well-targeted criteria for improving the professionalism of doctors, promoting more good doctor behaviours, providing guidance for regulating doctors' conduct and providing a reference for medical education and working performance reviews worldwide.

Diagnostic and Predictive Efficacy of Synovial Fluid Versus Serum C-Reactive Protein Levels for Periprosthetic Joint Infection and Reimplantation Success.

BACKGROUND: A 2-stage exchange revision for periprosthetic joint infection (PJI) is associated with major risks for reinfection. Although serum markers are frequently used for diagnosis, their effectiveness remains debatable. Synovial fluid markers may offer a more accurate diagnosis of PJI; however, the importance of these biomarkers, notably synovial fluid C-reactive protein (syCRP), remains controversial, particularly in the context of reimplantation. The present study aimed to clarify these diagnostic uncertainties by evaluating the diagnostic efficacy of syCRP versus serum CRP (seCRP) levels in the context of PJI and recurring or persisting infections before reimplantation. METHODS: A total of 186 patients were enrolled and divided into 2 groups: aseptic revision (n = 112) and PJI revision (n = 74). Of the PJI group, 65 were categorized as success and 9 as failure, based on the presence of recurrent or persistent infection before reimplantation. The syCRP and seCRP levels and their changes were assessed preoperatively and in the first-stage and second-stage revisions. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) were analyzed. RESULTS: Both seCRP and syCRP levels were significantly elevated in the PJI group compared with the aseptic group (P < .001). The ROC curve analysis highlighted the enhanced diagnostic accuracy of syCRP for PJI, with an AUC of 0.93 versus 0.80 for seCRP. Furthermore, syCRP proved to be more reliable in predicting reimplantation success, exhibiting an AUC of 0.86 versus 0.63 for seCRP. In evaluating trends in CRP levels to determine reimplantation timing, changes in syCRP levels demonstrated superior diagnostic utility, exhibiting an AUC of 0.79 versus 0.63 for changes in seCRP levels. CONCLUSIONS: In assessing PJI and infections before reimplantation, syCRP may offer enhanced accuracy compared with seCRP. Nevertheless, variations in both syCRP and seCRP levels did not consistently predict the outcome of reimplantation.

Integrated Cardiomyocyte-Based Biosensing Platform for Electroporation-Triggered Intracellular Recording in Parallel with Delivery Efficiency Evaluation.

Electroporation is a proven technique that can record action potential of cardiomyocytes and serve for biomolecular delivery. To ensure high cell viability, micro-nanodevices cooperating with low-voltage electroporation are frequently utilized in research, and the effectiveness of delivery for intracellular access is typically assessed using an optical imaging approach like flow cytometry. However, the efficiency of in situ biomedical studies is hampered by the intricacy of these analytical approaches. Here, we develop an integrated cardiomyocyte-based biosensing platform to effectively record action potential and evaluate the electroporation quality in terms of viability, delivery efficiency, and mortality. The ITO-MEA device of the platform possesses sensing/stimulating electrodes which combines with the self-developed system to achieve intracellular action potential recording and delivery by electroporation trigger. Moreover, the image acquisition processing system analyzes various parameters effectively to assess delivery performance. Therefore, this platform has the potential for drug delivery therapy and pathology research for cardiology.

Scalable and Robust Hollow Nanopillar Electrode for Enhanced Intracellular Action Potential Recording.

Electrophysiology is a unique biomarker of the electrogenic cells that can perform a disease investigation or drug assessment. In the recent decade, vertical nanoelectrode arrays can successfully achieve a high-quality intracellular electrophysiological study in electrogenic cells and their networks. However, a high success rate and high-quality and long-term intracellular recording using low-cost nanostructures is still a considerable challenge. Herein, we develop a scalable and robust hollow nanopillar electrode to achieve enhanced intracellular recording of cardiomyocytes. The template-based synthesis of vertical hollow nanopillars is compatible with large-scale and efficient microfabrication processes and is convenient to regulate the geometry of hollow nanopillars. Compared with the conventional same-size planar electrode, the regulating height of a hollow nanopillar can achieve high-quality and prolonged intracellular recordings, which can improve the cell-electrode interface for tight coupling and effective electroporation. It is demonstrated that the geometry regulation of a nanostructure is a powerful strategy to enhance intracellular recording.

Dynamic and Label-Free Sensing of Cardiomyocyte Responses to Nanosized Vesicles for Cardiac Oxidative Stress Injury Therapy.

Cardiac oxidative stress is a significant phenotype of myocardial infarction disease, a leading cause of global health threat. There is an urgent need to develop innovative therapies. Nanosized extracellular vesicle (nEV)-based therapy shows promise, yet real-time monitoring of cardiomyocyte responses to nEVs remains a challenge. In this study, a dynamic and label-free cardiomyocyte biosensing system using microelectrode arrays (MEAs) was constructed. Cardiomyocytes were cultured on MEA devices for electrophysiological signal detection and treated with nEVs from E. coli, gardenia, HEK293 cells, and mesenchymal stem cells (MSC), respectively. E. coli-nEVs and gardenia-nEVs induced severe paroxysmal fibrillation, revealing distinct biochemical communication compared to MSC-nEVs. Principal component analysis identified variations and correlations between nEV types. MSC-nEVs enhanced recovery without inducing arrhythmias in a H2O2-induced oxidative stress injury model. This study establishes a fundamental platform for assessing biochemical communication between nEVs and cardiomyocytes, offering new avenues for understanding nEVs' functions in the cardiovascular system.

Optimizing the Cell-Nanostructure Interface: Nanoconcave/Nanoconvex Device for Intracellular Recording of Cardiomyocytes.

Nanostructures are powerful components for the development of high-performance nanodevices. Revealing and understanding the cell-nanostructure interface are essential for improving and guiding nanodevice design for investigations of cell physiology. For intracellular electrophysiological detection, the cell-nanostructure interface significantly affects the quality of recorded intracellular action potentials and the application of nanodevices in cardiology research and pharmacological screening. Most of the current investigations of biointerfaces focus on nanovertical structures, and few involve nanoconcave structures. Here, we design both nanoconvex and nanoconcave devices to perform intracellular electrophysiological recordings. The amplitude, signal-to-noise ratio, duration, and repeatability of the recorded intracellular electrophysiological signals provide a multifaceted characterization of the cell-nanostructure interface. We demonstrate that devices based on both convex and concave nanostructures can create tight coupling, which facilitates high-quality and stable intracellular recordings and paves the way for precise electrophysiological study.

The inhibition of Beclin1-dependent autophagy sensitizes PTC cells to ABT737-induced death.

ABT737 is used as a specific BCL2 inhibitor, which can treat papillary thyroid carcinoma (PTC). However, the effect of ABT737 on PTC cell apoptosis is limited. Moreover, BCL2 inhibition causes the activation of Beclin1-dependent autophagy. Our study aimed to explore the effects of autophagy and Beclin1 on ABT737 efficacy in PTC. The experimental data showed that ABT737 synchronously enhanced autophagic activity and apoptosis level in PTC cells. ABT737 also promoted the dissociation of BCL2-Beclin1 and BCL2-Bax complexes. Autophagy inhibitors, Bafilomycin A1 and 3-MA, enhanced the inhibitory effect of ABT737 on the survival and function in PTC cells. Consistently, autophagy inhibition with Beclin1 pharmacological inhibitor (spautin-1) also enhanced the efficacy of ABT737. Additionally, ABT737 at low-dose promoted LC3 conversion in PTC cells, and did not affect PTC cell apoptosis and survival. However, The efficacy of low-dose of ABT737 in PTC cell apoptosis and survival was displayed with the addition of Bafilomycin A1, 3-MA or spautin-1. In conclusion, the limited role of ABT737 in PTC cell apoptosis is attributed to its promoting effect on Beclin1-dependent autophagy. Therefore, autophagy inhibition based on Beclin1 downregulation can enhance the sensitivity of PTC cells to ABT737-induced death.

Microarray Chip and Method for Simultaneous and Highly Consistent Electroporation of Multiple Cells of Different Sizes.

Cell electroporation is an important cell manipulation technology to artificially transfer specific extracellular components into cells. However, the consistency of substance transport during the electroporation process is still an issue due to the wide size distribution of the natural cells. In this study, a cell electroporation microfluidic chip based on a microtrap array is proposed. The microtrap structure was optimized for single-cell capture and electric field focusing. The effects of the cell size on the cell electroporation in the microchip were investigated through simulation and experiment methods using the giant unilamellar vesicle as the simplified cell model, and a numerical model of a uniform electric field was used as a comparison. Compared with the uniform electric field, a lower threshold electric field is required to induce electroporation and produces a higher transmembrane voltage on the cell under a specific electric field in the microchip, showing an improvement in cell viability and electroporation efficiency. The larger perforated area produced on the cells in the microchip under a specific electric field allows a higher substance transfer efficiency, and the electroporation results are less affected by the cell size, which is beneficial for improving substance transfer consistency. Furthermore, the relative perforation area increases with the decrease of the cell diameter in the microchip, which is exactly opposite to that in a uniform electric field. By manipulating the electric field applied to the microtrap individually, a consistent proportion of substance transfer during electroporation of cells with different sizes can be achieved.

OsFAR1 is involved in primary fatty alcohol biosynthesis and promotes drought tolerance in rice.

MAIN CONCLUSION: OsFAR1 encodes a fatty acyl-CoA reductase involved in biosynthesis of primary alcohols and plays an important role in drought stress response in rice. Cuticular waxes cover the outermost surface of terrestrial plants and contribute to inhibiting nonstomatal water loss and improving plant drought resistance. Primary alcohols are the most abundant components in the leaf cuticular waxes of rice (Oryza sativa), but the biosynthesis and regulation of primary alcohol remain largely unknown in rice. Here, we identified and characterized an OsFAR1 gene belonging to the fatty acyl-CoA reductases (FARs) via a homology-based approach in rice. OsFAR1 was activated by abiotic stresses and abscisic acid, resulting in increased production of primary alcohol in rice. Heterologous expression of OsFAR1 enhanced the amounts of C22:0 and C24:0 primary alcohols in yeast (Saccharomyces cerevisiae) and C24:0 to C32:0 primary alcohols in Arabidopsis. Similarly, OsFAR1 overexpression significantly increased the content of C24:0 to C30:0 primary alcohols on rice leaves. Finally, OsFAR1 overexpression lines exhibited reduced cuticle permeability and enhanced drought tolerance in rice and Arabidopsis. Taken together, our results demonstrate that OsFAR1 is involved in rice primary alcohol biosynthesis and plays an important role in responding to drought and other environmental stresses.

ECERIFERUM1-6A is required for the synthesis of cuticular wax alkanes and promotes drought tolerance in wheat.

Cuticular waxes cover the aerial surfaces of land plants and protect them from various environmental stresses. Alkanes are major wax components and contribute to plant drought tolerance, but the biosynthesis and regulation of alkanes remain largely unknown in wheat (Triticum aestivum L.). Here, we identified and functionally characterized a key alkane biosynthesis gene ECERIFERUM1-6A (TaCER1-6A) from wheat. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated knockout mutation in TaCER1-6A greatly reduced the contents of C27, C29, C31, and C33 alkanes in wheat leaves, while TaCER1-6A overexpression significantly increased the contents of these alkanes in wheat leaves, suggesting that TaCER1-6A is specifically involved in the biosynthesis of C27, C29, C31, and C33 alkanes on wheat leaf surfaces. TaCER1-6A knockout lines exhibited increased cuticle permeability and reduced drought tolerance, whereas TaCER1-6A overexpression lines displayed reduced cuticle permeability and enhanced drought tolerance. TaCER1-6A was highly expressed in flag leaf blades and seedling leaf blades and could respond to abiotic stresses and abscisic acid. TaCER1-6A was located in the endoplasmic reticulum, which is the subcellular compartment responsible for wax biosynthesis. A total of three haplotypes (HapI/II/III) of TaCER1-6A were identified in 43 wheat accessions, and HapI was the dominant haplotype (95%) in these wheat varieties. Additionally, we identified two R2R3-MYB transcription factors TaMYB96-2D and TaMYB96-5D that bound directly to the conserved motif CAACCA in promoters of the cuticular wax biosynthesis genes TaCER1-6A, TaCER1-1A, and fatty acyl-CoA reductase4. Collectively, these results suggest that TaCER1-6A is required for C27, C29, C31, and C33 alkanes biosynthesis and improves drought tolerance in wheat.

Synchronously Producing H2 and Purifying Methyl Orange-Polluted Water through the Reaction of an Al-GaInSn Alloy Plate and H2O.

Hydrogen gas (H2) as a fuel has the advantages of high energy density (122 kJ g-1) and zero carbon emissions. To meet the growing demand for H2 in the future, green, efficient, and convenient production technologies must be developed. The Al-H2O reaction, which produces H2 by reacting aluminum (Al) with water (H2O), is considered a rapid method for producing H2. However, Al-H2O creates a protective oxide layer on the surface of Al, preventing the production of H2. In this study, we developed a simple method for forming Al-GaInSn alloy by brushing GaInSn-Al2O3 grease onto an Al plate to form an Al/GaInSn-Al2O3/Al sandwich structure. Al2O3 in the sample supports GaInSn, prevents the leakage of GaInSn, and promotes its penetration into the Al lattice to form Al-GaInSn alloy. By forming a liquid phase within the alloy, GaInSn increases the accessibility of Al to the reaction. As a result, the Al-GaInSn alloy can rapidly react with pure H2O to produce H2 at room temperature conditions, with yields as high as ∼93.2%. It was interesting to find that dye-polluted water (methyl orange) could be synchronically purified by the Al-H2O reaction at the same time.

Boosting the performance of an iontophoretic biosensing system with a graphene aerogel and Prussian blue for highly sensitive and noninvasive glucose monitoring.

Diabetes and impaired glucose regulation (IGR) threaten the lives and health of numerous patients. Interstitial fluid (ISF) glucose, displaying an excellent correlation with blood glucose, is highly desired to address the limitations of invasive and minimally invasive glucose detection. Herein, we present a screen-printed iontophoretic biosensing system to extract ISF noninvasively and perform in situ instant glucose detection. A three-dimensional graphene aerogel combined with Prussian blue (GA@PB) was introduced as an electron mediator, providing suitable support for glucose oxidase (GOx) immobilization, highly boosting the detection sensitivity. Additionally, a self-made diffuse cell and an ex vivo model were developed to demonstrate the efficacy of ISF extraction based on reverse iontophoresis technology. Highly sensitive and accurate detection of ISF glucose could be achieved with an LOD of 0.26 mM over a 0-15 mM range. Finally, tests on healthy volunteers were conducted to further validate the feasibility of this as-proposed system. Combined with its well flexible and biocompatible features, it holds considerable prospects in the development of wireless wearable biosensors for continuous blood glucose monitoring.

TAT-Beclin 1 represses the carcinogenesis of DUSP4-positive PTC by enhancing autophagy.

BACKGROUND: DUSP4 is a pro-tumorigenic molecule of papillary thyroid carcinoma (PTC). DUSP4 also exists as an autophagic regulator. Moreover, DUSP4, as a negative regulator of MAPK, can prevent Beclin 1 from participating in autophagic response. This study aimed to explore whether TAT-Beclin 1, a recombinant protein of Beclin 1, could inhibit the tumorigenesis of DUSP4-positive PTC by regulating autophagy. METHODS: First, we divided PTC tissues into three groups according to DUSP4 expression levels by immunohistochemical analyses, and evaluated the relationship between autophagic molecules (Beclin 1 and LC3II) and DUSP4 using Western blotting assays. After overexpression of DUSP4 by lentiviral transduction, the in vitro and in vivo roles of TAT-Beclin 1 on DUSP4-overexpressed PTC cells were assessed (including autophagic activity, cell survival and function, and tumor growth). The roles of TAT-Beclin 1 in the survival of DUSP4-silenced PTC cells were also evaluated. RESULTS: Our results showed that the expression levels of autophagic proteins decreased with the increase of DUSP4 expression in PTC tissues. In PTC cells, DUSP4 overexpression-inhibited autophagic activity (including Beclin 1 expression, LC3 conversion rate and LC3-puncta formation) and -promoted cell proliferation and migration were reversed by TAT-Beclin 1 administration. In vivo assays also showed that DUSP4-overexpressed PTC cells had stronger tumorigenic ability and weaker autophagic activity, which was blocked by TAT-Beclin 1 administration. CONCLUSION: TAT-Beclin 1, as an autophagic promoter, could repress the carcinogenesis of DUSP4-positive PTC, which implies that the use of TAT-Beclin 1 for the PTC patients' treatment might be determined according to the DUSP4 level in their tumors.

Atomic understanding of the strain-induced electrocatalysis from DFT calculation: progress and perspective.

Catalyst activity affects the reaction rate, and an increasing number of studies have shown that strain can significantly increase the electrocatalytic activity. Catalysts such as alloys and core-shell structures can modulate their properties through strain effects. Reasonable simulation techniques can be used to predict and design the catalytic performance based on understanding the strain action mechanism. Therefore, the methodological flow of theoretical simulations is summarised in this review. The mechanism underlying the strain-adsorption-reaction relationship is discussed using density functional theory (DFT) calculations. An introduction to DFT is given first, followed by a quick rundown of the strain classification and application. Typical electrocatalytic reactions, namely, the hydrogen and oxygen evolution reactions and oxygen reduction reaction, are taken as examples. After briefly explaining these reactions, the relevant studies on simulating the strain to tune the catalyst performance are covered. The simulation methods are summarised and analysed to observe the effects of strain on electrocatalytic properties. Finally, a summary of the issues with simulated strain-assisted design and a discussion on the perspectives and forecasts for the future design of effective catalysts are provided.

Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca2+-permeable AMPA receptors.

Exposure to loud sound damages the postsynaptic terminals of spiral ganglion neurons (SGNs) on cochlear inner hair cells (IHCs), resulting in loss of synapses, a process termed synaptopathy. Glutamatergic neurotransmission via α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type receptors is required for synaptopathy, and here we identify a possible involvement of GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) using IEM-1460, which has been shown to block GluA2-lacking AMPARs. In CBA/CaJ mice, a 2-h exposure to 100-dB sound pressure level octave band (8 to 16 kHz) noise results in no permanent threshold shift but does cause significant synaptopathy and a reduction in auditory brainstem response (ABR) wave-I amplitude. Chronic intracochlear perfusion of IEM-1460 in artificial perilymph (AP) into adult CBA/CaJ mice prevented the decrease in ABR wave-I amplitude and the synaptopathy relative to intracochlear perfusion of AP alone. Interestingly, IEM-1460 itself did not affect the ABR threshold, presumably because GluA2-containing AMPARs can sustain sufficient synaptic transmission to evoke low-threshold responses during blockade of GluA2-lacking AMPARs. On individual postsynaptic densities, we observed GluA2-lacking nanodomains alongside regions with robust GluA2 expression, consistent with the idea that individual synapses have both CP-AMPARs and Ca2+-impermeable AMPARs. SGNs innervating the same IHC differ in their relative vulnerability to noise. We found local heterogeneity among synapses in the relative abundance of GluA2 subunits that may underlie such differences in vulnerability. We propose a role for GluA2-lacking CP-AMPARs in noise-induced cochlear synaptopathy whereby differences among synapses account for differences in excitotoxic susceptibility. These data suggest a means of maintaining normal hearing thresholds while protecting against noise-induced synaptopathy, via selective blockade of CP-AMPARs.