Retinylidene chromophore hydrolysis from mammalian visual and non-visual opsins.

Rhodopsin (Rho) and cone opsins are essential for detection of light. They respond via photoisomerization, converting their Schiff-base-adducted 11-cis-retinylidene chromophores to the all-trans configuration, eliciting conformational changes to activate opsin signaling. Subsequent Schiff-base hydrolysis releases all-trans-retinal, initiating two important cycles that maintain continuous vision-the Rho photocycle and visual cycle pathway. Schiff-base hydrolysis has been thoroughly studied with photoactivated Rho but not with cone opsins. Using established methodology, we directly measured the formation of Schiff-base between retinal chromophores with mammalian visual and nonvisual opsins of the eye. Next, we determined the rate of light-induced chromophore hydrolysis. We found that retinal hydrolysis from photoactivated cone opsins was markedly faster than from photoactivated Rho. Bovine retinal G protein-coupled receptor (bRGR) displayed rapid hydrolysis of its 11-cis-retinylidene photoproduct to quickly supply 11-cis-retinal and re-bind all-trans-retinal. Hydrolysis within bRGR in native retinal pigment epithelium microsomal membranes was >6-times faster than that of bRGR purified in detergent micelles. N-terminal-targeted antibodies significantly slowed bRGR hydrolysis, while C-terminal antibodies had no effect. Our study highlights the much faster photocycle of cone opsins relative to Rho and the crucial role of RGR in chromophore recycling in daylight. By contrast, in our experimental conditions, bovine peropsin did not form pigment in the presence of all-trans-retinal nor with any mono-cis retinal isomers, leaving uncertain the role of this opsin as a light sensor.

A short story on how chromophore is hydrolyzed from rhodopsin for recycling.

The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century's worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff-base linked 11-cis-retinylidene chromophore of rhodopsin, converting it to the all-trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11-cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all-trans-retinylidene agonist.

Chromophore hydrolysis and release from photoactivated rhodopsin in native membranes.

For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all-trans-retinal, producing substrate for the visual cycle and apo-opsin available for regeneration with 11-cis-retinal. The kinetics of this hydrolysis has yet to be described for rhodopsin in its native membrane environment. We developed a method consisting of simultaneous denaturation and chromophore trapping by isopropanol/borohydride, followed by exhaustive protein digestion, complete extraction, and liquid chromatography-mass spectrometry. Using our method, we tracked Rho* hydrolysis, the subsequent formation of N-retinylidene-phosphatidylethanolamine (N-ret-PE) adducts with the released all-trans-retinal, and the reduction of all-trans-retinal to all-trans-retinol. We found that hydrolysis occurred faster in native membranes than in detergent micelles typically used to study membrane proteins. The activation energy of the hydrolysis in native membranes was determined to be 17.7 ± 2.4 kcal/mol. Our data support the interpretation that metarhodopsin II, the signaling state of rhodopsin, is the primary species undergoing hydrolysis and release of its all-trans-retinal. In the absence of NADPH, free all-trans-retinal reacts with phosphatidylethanolamine (PE), forming a substantial amount of N-ret-PE (∼40% of total all-trans-retinal at physiological pH), at a rate that is an order of magnitude faster than Rho* hydrolysis. However, N-ret-PE formation was highly attenuated by NADPH-dependent reduction of all-trans-retinal to all-trans-retinol. Neither N-ret-PE formation nor all-trans-retinal reduction affected the rate of hydrolysis of Rho*. Our study provides a comprehensive picture of the hydrolysis of Rho* and the release of all-trans-retinal and its reentry into the visual cycle, a process in which alteration can lead to severe retinopathies.

Unusual Raman Enhancement Effect of Ultrathin Copper Sulfide.

In surface-enhanced Raman spectroscopy (SERS), 2D materials are explored as substrates owing to their chemical stability and reproducibility. However, they exhibit lower enhancement factors (EFs) compared to noble metal-based SERS substrates. This study demonstrates the application of ultrathin covellite copper sulfide (CuS) as a cost-effective SERS substrate with a high EF value of 7.2 × 104 . The CuS substrate is readily synthesized by sulfurizing a Cu thin film at room temperature, exhibiting a Raman signal enhancement comparable to that of an Au noble metal substrate of similar thickness. Furthermore, computational simulations using the density functional theory are employed and time-resolved photoluminescence measurements are performed to investigate the enhancement mechanisms. The results indicate that polar covalent bonds (Cu─S) and strong interlayer interactions in the ultrathin CuS substrate increase the probability of charge transfer between the analyte molecules and the CuS surface, thereby producing enhanced SERS signals. The CuS SERS substrate demonstrates the selective detection of various dye molecules, including rhodamine 6G, methylene blue, and safranine O. Furthermore, the simplicity of CuS synthesis facilitates large-scale production of SERS substrates with high spatial uniformity, exhibiting a signal variation of less than 5% on a 4-inch wafer.

Evolution of Local Structural Motifs in Colloidal Quantum Dot Semiconductor Nanocrystals Leading to Nanofaceting.

Colloidal nanocrystals (NCs) have shown remarkable promise for optoelectronics, energy harvesting, photonics, and biomedical imaging. In addition to optimizing quantum confinement, the current challenge is to obtain a better understanding of the critical processing steps and their influence on the evolution of structural motifs. Computational simulations and electron microscopy presented in this work show that nanofaceting can occur during nanocrystal synthesis from a Pb-poor environment in a polar solvent. This could explain the curved interfaces and the olivelike-shaped NCs observed experimentally when these conditions are employed. Furthermore, the wettability of the PbS NCs solid film can be further modified via stoichiometry control, which impacts the interface band bending and, therefore, processes such as multiple junction deposition and interparticle epitaxial growth. Our results suggest that nanofaceting in NCs can become an inherent advantage when used to modulate band structures beyond what is traditionally possible in bulk crystals.

Facile one-pot iodine gas phase doping on 2D MoS2/CuS FET at room temperature.

Electronic devices composed of semiconducting two-dimensional (2D) materials and ultrathin 2D metallic electrode materials, accompanying synergistic interactions and extraordinary properties, are becoming highly promising for future flexible and transparent electronic and optoelectronic device applications. Unlike devices with bulk metal electrode and 2D channel materials, devices with ultrathin 2D electrode and 2D channel are susceptible to chemical reactions in both channel and electrode surface due to the high surface to volume ratio of the 2D structures. However, so far, the effect of doping was primary concerned on the channel component, and there is lack of understanding in terms of how to modulate electrical properties of devices by engineering electrical properties of both the metallic electrode and the semiconducting channel. Here, we propose the novel, one-pot doping of the field-effect transistor (FET) based on 2D molybdenum disulfide (MoS2) channel and ultrathin copper sulfide (CuS) electrodes under mild iodine gas environment at room temperature, which simultaneously modulates electrical properties of the 2D MoS2channel and 2D CuS electrode in a facile and cost-effective way. After one-pot iodine doping, effective p-type doping of the channel and electrode was observed, which was shown through decreased off current level, improvedIon/Ioffratio and subthreshold swing value. Our results open up possibility for effectively and conveniently modulating electrical properties of FETs made of various 2D semiconductors and ultrathin contact materials without causing any detrimental damage.

Pyrocinchonimides Conjugate to Amine Groups on Proteins via Imide Transfer.

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes. Despite their similarity to maleimides, pyrocinchonimides do not react with free thiols. Though both lysine residues and the N-termini of proteins can receive the transferred imide, the reaction also exhibits a marked preference for certain amines that cannot solely be ascribed to solvent accessibility. This property is peculiar among amine-targeting reactions and can reduce combinatorial diversity when many available reactive amines are available, such as in the formation of antibody-drug conjugates. Unlike amides, the modification undergoes very slow reversion under high pH conditions. The reaction offers a thermodynamically controlled route to single or multiple modifications of proteins for a wide range of applications.

Strain-Mediated Interlayer Coupling Effects on the Excitonic Behaviors in an Epitaxially Grown MoS2/WS2 van der Waals Heterobilayer.

van der Waals heterostructures composed of two different monolayer crystals have recently attracted attention as a powerful and versatile platform for studying fundamental physics, as well as having great potential in future functional devices because of the diversity in the band alignments and the unique interlayer coupling that occurs at the heterojunction interface. However, despite these attractive features, a fundamental understanding of the underlying physics accounting for the effect of interlayer coupling on the interactions between electrons, photons, and phonons in the stacked heterobilayer is still lacking. Here, we demonstrate a detailed analysis of the strain-dependent excitonic behavior of an epitaxially grown MoS2/WS2 vertical heterostructure under uniaxial tensile and compressive strain that enables the interlayer interactions to be modulated along with the electronic band structure. We find that the strain-modulated interlayer coupling directly affects the characteristic combined vibrational and excitonic properties of each monolayer in the heterobilayer. It is further revealed that the relative photoluminescence intensity ratio of WS2 to MoS2 in our heterobilayer increases monotonically with tensile strain and decreases with compressive strain. We attribute the strain-dependent emission behavior of the heterobilayer to the modulation of the band structure for each monolayer, which is dictated by the alterations in the band gap transitions. These findings present an important pathway toward designing heterostructures and flexible devices.

Stabilization of Lattice Oxygen Evolution Reactions in Oxophilic Ce-Mediated Bi/BiCeO1.8H Electrocatalysts for Efficient Anion Exchange Membrane Water Electrolyzers.

The lattice oxygen mechanism (LOM) offers an efficient reaction pathway for oxygen evolution reactions (OERs) in energy storage and conversion systems. Owing to the involvement of active lattice oxygen enhancing electrochemical activity, addressing the structural and electrochemical stabilities of LOM materials is crucial. Herein, a heterostructure (Bi/BiCeO1.8H) containing abundant under-coordinated oxygen atoms having oxygen nonbonding states is synthesized by a simple electrochemical deposition method. Given the difference in reduction potentials between Bi and Ce, partially reduced Bi nanoparticles and surrounding under-coordinated oxygen atoms are generated in BiCeO1.8H. It is found that the lattice oxygen can be activated as a reactant of the OER when the valence state of Bi increases to Bi5+, leading to increased metal-oxygen covalency and that the oxophilic Ce3+/4+ redox couple can maintain the Bi nanoparticles and surrounding under-coordinated oxygen atoms by preventing over-oxidation of Bi. The anion exchange membrane water electrolyzer with Bi/BiCeO1.8H exhibits a low cell voltage of 1.79 V even at a high practical current density of 1.0 A cm-2. Furthermore, the cell performance remains significantly stable over 100 h with only a 2.2% increase in the initial cell voltage, demonstrating sustainable lattice oxygen redox.

Mannose Supplementation Curbs Liver Steatosis and Fibrosis in Murine MASH by Inhibiting Fructose Metabolism.

Metabolic dysfunction-associated steatohepatitis (MASH) can progress to cirrhosis and liver cancer. There are no approved medical therapies to prevent or reverse disease progression. Fructose and its metabolism in the liver play integral roles in MASH pathogenesis and progression. Here we focus on mannose, a simple sugar, which dampens hepatic stellate cell activation and mitigates alcoholic liver disease in vitro and in vivo . In the well-validated FAT-MASH murine model, oral mannose supplementation improved both liver steatosis and fibrosis at low and high doses, whether administered either at the onset of the model ("Prevention") or at week 6 of the 12-week MASH regimen ("Reversal"). The in vivo anti-fibrotic effects of mannose supplementation were validated in a second model of carbon tetrachloride-induced liver fibrosis. In vitro human and mouse primary hepatocytes revealed that the anti-steatotic effects of mannose are dependent on the presence of fructose, which attenuates expression of ketohexokinase (KHK), the main enzyme in fructolysis. KHK is decreased with mannose supplementation in vivo and in vitro, and overexpression of KHK abrogated the anti-steatotic effects of mannose. Our study identifies mannose as a simple, novel therapeutic candidate for MASH that mitigates metabolic dysregulation and exerts anti-fibrotic effects.

UCI EyeMobile Exam Findings from School Children Following on-Site Screening.

Purpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss. Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency. Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), and amblyopia risk (14.4%). A majority (65.0%) of those examined received prescription spectacles from UCI EyeMobile, with around a third requiring a new or updated prescription. The frequency of REs and amblyopia and the spectacle prescription rate were uniform across OC congressional districts. Myopia and amblyopia risk was positively and negatively associated with household income, respectively. Conclusion: The UCI EyeMobile for Children serves as a vital vision care program, providing free vision screening, comprehensive eye examinations, and spectacles. A significant number of children required examination, and a high frequency of REs and amblyopia were detected in examined children, with subsequent provision of prescription spectacles to most children.

Exploring Pediatric Vision Care: Insights from Five Years of Referral Cases in the UCI Eye Mobile and Implications of COVID-19.

PURPOSE: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses. RESULTS: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age (P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender (P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years (P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76). CONCLUSIONS: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XXX-XXX.].

Analysis of inflammation-related nigral degeneration and locomotor function in DJ-1(-/-) mice.

BACKGROUND: Complex interactions involving genetic susceptibility and environmental factors are thought to underlie the pathogenesis of Parkinson's disease (PD). Although the role of inflammatory processes in modulating risk for development of PD has yet to be fully understood, prospective studies suggest that chronic use of NSAIDs reduce the incidence of PD. Loss-of-function mutations in the DJ-1 gene cause a rare form of familial PD with an autosomal recessive pattern of inheritance; however, DJ-1-/- mice do not display nigrostriatal pathway degeneration, suggesting that additional factors such as inflammation may be needed to induce neurodegeneration on the background of DJ-1 gene mutations. Neuroinflammation causes oxidative stress and, based on evidence that DJ-1 plays a protective role against oxidative stress, we investigated whether DJ-1-/- mice display increased vulnerability to inflammation-induced nigral degeneration. METHODS: We exposed adult wild-type and DJ-1-/- mice to repeated intranasal administration of soluble TNF (inTNF) or repeated intraperitoneal injections of low-dose lipopolysaccharide (LPS) or saline vehicle. We measured locomotor performance using a variety of behavior tasks, striatal dopamine (DA) content by HPLC, DA neuron (TH+ cells) and total neuron (NeuN+ cells) number in the substantia nigra pars compacta and ventral tegmental area by unbiased stereology, number of Iba1-positive microglia, and mRNA levels of inflammatory and oxidative stress genes by quantitative PCR in the midbrain, cortex and isolated peritoneal macrophages of DJ-1-/- and wild-type mice. RESULTS: We found that chronic LPS injections induced similar neuroinflammatory responses in the midbrains of DJ-1-/- mice and wild-type mice and neither group developed locomotor deficits or nigral degeneration. inTNF administration did not appear to induce neuroinflammatory responses in LPS-treated wild-type or DJ-1-/- mice. The lack of vulnerability to inflammation-induced nigral degeneration was not due to enhanced anti-oxidant gene responses in the midbrains of DJ-1-/- mice which, in fact, displayed a blunted response relative to that of wild-type mice. Peripheral macrophages from wild-type and DJ-1-/- mice displayed similar basal and LPS-induced inflammatory and oxidative stress markers in vitro. CONCLUSIONS: Our studies indicate that DJ-1-/- mice do not display increased vulnerability to inflammation-related nigral degeneration in contrast to what has been reported for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. We conclude that either DJ-1 does not have a critical role in protecting DA neurons against inflammation-induced oxidative stress and/or there is compensatory gene expression in the midbrain of DJ-1-/- mice that renders them resistant to the cytotoxic effects triggered by chronic peripheral inflammation.

Engineered molecular stacking crystallinity of bar-coated TIPS-pentacene/polystyrene films for organic thin-film transistors.

Solution-based blended polymer materials are promising for electronic applications in many fields. However, determining a controllable method to achieve electronically active organic films through the practical liquid deposition process is very challenging. In this study, we suggest employing hybrid binary organic mixture inks (an insulating polymer polystyrene (PS)) and an organic semiconductor (6,13-bis(triisopropylsilylethnyl)pentacene (TIPS-pentacene)) to manage and enhance the characteristics of TIPS-pentacene organic layers using a bar-coating method. Binary mixtures with PS molecules can provide various microstructures, crystal orientations, and molecular stacking of the active TIPS-pentacene organic layers under the proper fabrication parameters during bar-coating. Varying the molecular weight of the PS mixture, weight percentage of the TIPS-pentacene, and deposition parameters, such as the bar-coating speed, direction, and contact angles between the crystal orientation of TIPS-pentacene and Au electrodes, is crucial to guarantee high-electronic properties. The electrodes with TIPS-pentacene/PS (MW = 4000) binary films at a 40 wt% TIPS-pentacene ratio demonstrate the outstanding room-temperature field-effect mobility of 1.215 cm2 V-1 s-1, four times higher than that of pure TIPS-pentacene transistors (100 wt%). The performance improvement of the TIPS-pentacene layers is highly attributed to the ideal spherulite structure and thick molecular stacking properties, which can guarantee favorable charge transport paths through organic films. These findings demonstrate a promising strategy for blending organic applications to improve the performance of organic electronic devices using practical fabrication processes.

Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.

Rhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six - a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding.

Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia.

In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.

Henoch-Schönlein purpura and crohn's disease: Expanding the range of association in pediatric patients.

The association of new onset Henoch-Schönlein purpura (HSP) and inflammatory bowel disease (IBD) has been reported in the setting of concomitant anti-TNF-ɑ treatment. We present two pediatric IBD cases who developed new onset HSP without such association. These cases add to the literature by suggesting an association between HSP and IBD in pediatric population. We discuss possible underlying pathophysiological mechanisms, suggesting some commonality with IgA nephropathy. Increased awareness for HSP in pediatric IBD patients regardless of anti-TNF- ɑ therapy involvement is important for timely recognition and appropriate multi-disciplinary management.

Electrochemically active hydroquinone-based redox mediator for flexible energy storage system with improved charge storing ability.

Electrochemically active redox mediators have been widely investigated in energy conversion/storage system to improve overall catalytic activities and energy storing ability by inducing favorable surface redox reactions. However, the enhancement of electrochemical activity from the utilization of redox mediators (RMs) is only confirmed through theoretical computation and laboratory-scale experiment. The use of RMs for practical, wearable, and flexible applications has been scarcely researched. Herein, for the first time, a wearable fiber-based flexible energy storage system (f-FESS) with hydroquinone (HQ) composites as a catalytically active RM is introduced to demonstrate its energy-storing roles. The as-prepared f-FESS-HQ shows the superior electrochemical performance, such as the improved energy storage ability (211.16 F L-1 and 29.3 mWh L-1) and long-term cyclability with a capacitance retention of 95.1% over 5000 cycles. Furthermore, the f-FESS-HQ can well maintain its original electrochemical properties under harsh mechanical stress (bending, knotting, and weaving conditions) as well as humid conditions in water and detergent solutions. Thus, the strategical use of electrochemically active RMs can provide the advanced solution for future wearable energy storage system.

Epidural electrical stimulation for spinal cord injury.

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

Room Temperature Wafer-Scale Synthesis of Highly Transparent, Conductive CuS Nanosheet Films via a Simple Sulfur Adsorption-Corrosion Method.

The development of highly conductive electrodes with robust mechanical durability and clear transmittance in the visible to IR spectral range is of great importance for future wearable/flexible electronic applications. In particular, low resistivity, robust flexibility, and wide spectral transparency have a significant impact on optoelectronic performance. Herein, we introduce a new class of covellite copper monosulfide (CuS) nanosheet films as a promising candidate for soft transparent conductive electrodes (TCEs). An atmospheric sulfur adsorption-corrosion phenomenon represents a key approach in our work for the achievement of wafer-scale CuS nanosheet films through systematic control of the neat Cu layer thickness ranging from 2 to 10 nm multilayers at room temperature. These nanosheet films provide outstanding conductivity (∼25 Ω sq-1) and high transparency (> 80%) in the visible to infrared region as well as distinct flexibility and long stability under air exposure, yielding a high figure-of-merit (∼60) that is comparable to that of conventional rigid metal oxide material-based TCEs. Our unique room temperature synthesis process delivers high quality CuS nanosheets on any arbitrary substrates in a short time (< 1 min) scale, thus guaranteeing the widespread use of highly producible and scalable device fabrication.