Nanoribbon Yarn with Versatile Inorganic Materials.

Nanomaterial-based yarns have been actively developed owing to their advantageous features, namely, high surface-area-to-volume ratios, flexibility, and unusual material characteristics such as anisotropy in electrical/thermal conductivity. The superior properties of the nanomaterials can be directly imparted and scaled-up to macro-sized structures. However, most nanomaterial-based yarns have thus far, been fabricated with only organic materials such as polymers, graphene, and carbon nanotubes. This paper presents a novel fabrication method for fully inorganic nanoribbon yarn, expanding its applicability by bundling highly aligned and suspended nanoribbons made from various inorganic materials (e.g., Au, Pd, Ni, Al, Pt, WO3, SnO2, NiO, In2O3, and CuO). The process involves depositing the target inorganic material on a nanoline mold, followed by suspension through plasma etching of the nanoline mold, and twisting using a custom-built yarning machine. Nanoribbon yarn structures of various functional inorganic materials are utilized for chemical sensors (Pd-based H2 and metal oxides (MOx)-based green gas sensors) and green energy transducers (water splitting electrodes/triboelectric nanogenerators). This method is expected to provide a comprehensive fabrication strategy for versatile inorganic nanomaterials-based yarns.

Ultra-Widefield-Guided Swept-Source OCT Findings of Peripheral Vitreoretinal Abnormality in Young Myopes.

PURPOSE: To evaluate the ultra-widefield fundus photography (UWF-FP)-guided swept-source OCT (SS-OCT) images of peripheral vitreoretinal abnormality (PVRA) in young asymptomatic myopes. DESIGN: Cross-sectional, single-center study. PARTICIPANTS: A total of 1966 eyes of 983 consecutive patients aged 18 to 42 years with refractive error in the spherical equivalent of < 0 diopters (D) who visited KEYE Eye Center, Seoul, Republic of Korea, for refractive surgery. METHODS: The prevalence of PVRA and their characteristics, including shape, location, presence of pigmentation, membrane, retinal breaks, and detachment, were evaluated. A logistic regression analysis was done to evaluate the risk factors of PVRA and the risk of retinal breaks or detachment among eyes with PVRA. RESULTS: Among 1966 eyes, 317 (16.1%) had PVRA, and 182 (57.4%) and 135 (42.6%) had focal and linear lesions, respectively. The risk of PVRA was increased with axial length of the eyes (odds ratio [OR], 1.238, 95% confidence interval [CI], 1.112-1.379, P < 0.001), corneal astigmatism (OR, 1.320, 95% CI, 1.148-1.519, P < 0.001), presence of discrete margins of different retinal reflectivity (DMDRR; indicating outer retinal disruption from abnormal vitreoretinal traction) (OR, 1.751, 95% CI, 1.334-2.300, P < 0.001), and posterior vitreous detachment (PVD) at the posterior pole of the retina (OR, 1.833, 95% CI, 1.352-2.485, P < 0.001). Among eyes with PVRA, patient age (OR, 1.063, 95% CI, 1.008-1.121, P = 0.025), linear lesions (OR, 15.234, 95% CI, 7.891-29.407, P < 0.001), and multiple lesions (OR, 3.432, 95% CI, 1.780-6.620, P < 0.001) were independently associated with the presence of retinal breaks or detachment. CONCLUSIONS: The follow-up for PVRA among young myopes should be personalized on the basis of their ocular characteristics, including asymmetric ocular expansion (axial length and astigmatism) and vitreoretinal interface status. The treatment plan for PVRA eyes should emphasize the greater risk of retinal breaks and detachment with increasing age and the presence of linear and multiple lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Choroidal arterial abnormality in central serous chorioretinopathy.

PURPOSE: To evaluate the choroidal arterial abnormality in central serous chorioretinopathy (CSC). METHODS: Fifty-two eyes from 52 patients with CSC were retrospectively evaluated. Arterial and venous ultrawide-field indocyanine green angiography were merged after color and transparency adjustments to compare the choroidal arterial and venous vasculature. Specifically, we evaluated whether the choroidal arteries directly fill the pachyvessel without interconnection of choriocapillaris (arterial pachyvessel; aPV). Then, the clinical characteristics of patients with and without arterial pachyvessel were compared. RESULTS: Pachyvessel under subretinal fluid was detected in 47 of 52 eyes (90.4%). An arterial pachyvessel was detected in eight of 52 eyes (15.4%). Of those eight eyes with arterial pachyvessel, seven (87.5%) showed sustained staining through the venous phase, suggesting they are arteriovenous shunt, while one eye (12.5%) showed diminished fluorescence in the venous phase, suggesting this pachyvessel was purely an artery. Patients with arterial pachyvessel experienced more CSC recurrences (non-aPV group: 2.09 ± 1.44 times vs. aPV group: 3.25 ± 1.28 times; p = 0.039) and pachychoroid neovasculopathy (PNV) development (non-aPV group: 2.3% vs. aPV group: 37.5%, p = 0.009). CONCLUSION: The presence of arterial pachyvessel in eyes with CSC may represent choroidal circulatory imbalance and focal shear stress to Bruch's membrane, leading to a chronic nature and PNV development.

Water-resistant free-standing DNA-complexed films with antioxidant and H2O2-responsive activity.

Water-insoluble DNA complexes are suitable for producing free-standing DNA films due to their low water sensitivity, which prevents their rapid degradation in aqueous environments. Here, we proposed two types of free-standing films that exhibit low dissolution rates in water: low molecular weight chitosan (LCS)-DNA films and phosphatidylcholine (PC)-cetyltrimethylammonium (CTMA)-DNA films. The structure and binding characteristics of the LCS-DNA and PC-CTMA-DNA complexes were investigated with UV-Vis spectroscopy and via the fluorescent characteristics of daunorubicin bound to them. A simple drop-casting method was then adopted for both complexes to fabricate free-standing films. An increase in antioxidant activity and water-resistance of the LCS-DNA DNA film was observed when the molar ratio of LCS to DNA was increased, but the dissolution rate of the LCS-DNA film was also dependent on the ionic strength of the dissolving solution. Fourteen days were required to dissolve the LCS-DNA film in deionized water, whereas immediate dissolution was observed in 1× phosphate-buffered saline (PBS). Deformation of the PC-CTMA-DNA film was accelerated by H2O2, such that the PC-CTMA-DNA film was degraded after 21 days of immersion in 1× PBS with H2O2. Due to the low dissolution rate in water and antioxidant activity, the free-standing LCS-DNA film should be able to store and protect embedded clinical materials, such as proteins and intercalating drugs, from moisture and enable localized delivery of treatments to designated sites. Also, the free-standing PC-CTMA-DNA film could be a biocompatible candidate for use as a membrane or sensor for detecting the levels of reactive oxygen species.

Clinical outcomes after implantation of extended depth-of-focus AcrySof® Vivity® intraocular lens in eyes with low-grade epiretinal membrane.

PURPOSE: To evaluate the clinical outcomes of extended depth-of-focus (EDoF) AcrySof® Vivity® intraocular lens in eyes with low-grade epiretinal membrane (ERM). METHODS: Forty-five eyes with low-grade ERM and history of Vivity implantation were compared with 50 age-matched controls with Vivity implantation and no ERM. Eyes with ERM showing widening of the outer nuclear layer and loss of the foveal depression, but no ectopic inner foveal layer or outer retinal defect were eligible. Corrected and uncorrected distant visual acuity (CDVA and UDVA), uncorrected intermediate and near visual acuity (UIVA and UNVA), contrast sensitivity detected by area under the log contrast sensitivity function (AULCSF), Strehl ratio, area ratio, and occurrence of dysphotopsia were compared between groups. RESULTS: UDVA and CDVA were similar between groups (UDVA: 0.01 ± 0.05 vs 0.03 ± 0.06, P = 0.154; CDVA: 0.00 ± 0.00 vs 0.00 ± 0.02, P = 0.125). UIVA and mesopic AULCSF were significantly worse in eyes with ERM compared to those with no ERM (UIVA: 0.09 ± 0.09 vs 0.14 ± 0.10, P = 0.028; mesopic AULCSF: 1.26 ± 0.15 vs 1.17 ± 0.10, P = 0.013). The occurrence of dysphotopsia was similar in both groups (glare: P = 0.465; halo: P = 0.218; starburst: P = 0.457). DISCUSSION: Eyes with low-grade ERM showed comparable outcomes to eyes without ERM after Vivity IOL implantation. Implantation of this newly developed EDoF IOL with low addition can be of benefit to eyes with low-grade, reversible ERM that is limited to the inner retina.

Visual outcomes of epiretinal membrane removal after diffractive-type multifocal intraocular lens implantation.

BACKGROUND: To assess visual outcomes of epiretinal membrane (ERM) removal in multifocal intraocular lens (MIOL)-implanted eyes, according to ERM stage. METHODS: Retrospective chart reviews were undertaken in patients with diffractive-type MIOL implants, each undergoing pars plana vitrectomy and ERM removal between February 2018 and November 2020 at Gyeongju St. Mary's Eye Clinic and KEYE Eye Center. Assessments focused on monocular uncorrected and corrected values of distant visual acuity (UDVA and CDVA) and uncorrected near visual acuity (UNVA) at postoperative 12 months according to the stage of ERM. RESULTS: The present study included a total of 49 MIOL-implanted eyes from 49 enrollees, 25 undergoing pars plana vitrectomy for ERM removal (11 eyes with Stage 2 and 14 eyes with Stage 3), and 24 acting as age-matched controls. There was a significant difference in UDVA and UNVA between control and Stage 3 ERM (UDVA; 0.01 ± 0.04 for control, and 0.07 ± 0.08 for stage 3 ERM, p = 0.035, UNVA; 0.03 ± 0.05 for control, and 0.13 ± 0.16 for Stage 3 ERM, p = 0.029). There were no significant differences in CDVA between groups (p = 0.121, ANOVA test). CONCLUSIONS: Eyes with Stage 3 ERM did not achieve visual acuity comparable to control eyes, suggesting the necessity of an early intervention for ERM in eyes with diffractive type MIOL. A meticulous preoperative retinal evaluation for ERM development is mandatory when planning diffractive-type MIOL implantation.

Wide-viewing full-color depthmap computer-generated holograms.

An efficient synthesis algorithm for wide-viewing full-color depthmap computer-generated holograms is proposed. We develop a precise computational algorithm integrating wave-optic geometry-mapping, color-matching, and noise-filtering to multiplex multiview elementary computer-generated holograms (CGHs) into a single high-definition CGH without three-dimensional perspective distortion or color dispersion. Computational parallelism is exploited to achieve significant computational efficiency improvement in the production throughput of full-color wide-viewing angle CGHs. The proposed algorithm is verified through the full-color binary hologram reconstruction experiments utilizing an off-axis R·G·B simultaneous illumination method, which suggests the feasibility of the full-color sub-wavelength binary spatial light modulator technology.

Influence of mild non-foveal involving epiretinal membrane on visual quality in eyes with multifocal intraocular lens implantation.

PURPOSE: To determine the influence of mild non-foveal involving epiretinal membrane (ERM) on visual outcome in eyes with multifocal intraocular lens (MIOL) implantation. METHODS: Patients with history of MIOL implantation were screened for the presence of ERM using spectral-domain optical coherence tomography (SD-OCT) at postoperative 6 months. Ninety-one eyes with mild non-foveal involving ERM and history of MIOL implantation were compared with 83 age-matched controls without ERM and history of MIOL implantation. The visual acuity (corrected and uncorrected) and visual quality (contrast sensitivity, Strehl ratio, area ratio, and higher-order aberrations; HOAs) of the eyes with mild non-foveal involving ERM were compared with the data of the age-matched control group. RESULTS: There was no difference in visual acuity between the groups at baseline and postoperative 6 months. The mild non-foveal involving ERM group showed significantly low contrast sensitivity at a visual angle of 4.0°, 2.5°, 1.0°, and 0.64° under scotopic conditions (P = .048, P = .025, P = .003, and P = .02, respectively) and 4.0°, 1.0°, and 0.64° under photopic conditions (P = .028, P = .002, and P = .001, respectively). The mean area ratio of the mild non-foveal involving ERM group was 45.13 ± 10.93, which was significantly lower than that of the control group, which measured 50.34 ± 12.66 (P = .044). CONCLUSION: A mild non-foveal involving ERM has no effect on visual acuity, but it reduces visual quality in eyes with MIOL implantation. A thorough screening using SD-OCT is warranted for this condition when considering MIOL implantation.

Increased Lysosomal Exocytosis Induced by Lysosomal Ca2+ Channel Agonists Protects Human Dopaminergic Neurons from α-Synuclein Toxicity.

The accumulation of misfolded proteins is a common pathological feature of many neurodegenerative disorders, including synucleinopathies such as Parkinson's disease (PD), which is characterized by the presence of α-synuclein (α-syn)-containing Lewy bodies. However, although recent studies have investigated α-syn accumulation and propagation in neurons, the molecular mechanisms underlying α-syn transmission have been largely unexplored. Here, we examined a monogenic form of synucleinopathy caused by loss-of-function mutations in lysosomal ATP13A2/PARK9. These studies revealed that lysosomal exocytosis regulates intracellular levels of α-syn in human neurons. Loss of PARK9 function in patient-derived dopaminergic neurons disrupted lysosomal Ca2+ homeostasis, reduced lysosomal Ca2+ storage, increased cytosolic Ca2+, and impaired lysosomal exocytosis. Importantly, this dysfunction in lysosomal exocytosis impaired α-syn secretion from both axons and soma, promoting α-syn accumulation. However, activation of the lysosomal Ca2+ channel transient receptor potential mucolipin 1 (TRPML1) was sufficient to upregulate lysosomal exocytosis, rescue defective α-syn secretion, and prevent α-syn accumulation. Together, these results suggest that intracellular α-syn levels are regulated by lysosomal exocytosis in human dopaminergic neurons and may represent a potential therapeutic target for PD and other synucleinopathies.SIGNIFICANCE STATEMENT Parkinson's disease (PD) is the second most common neurodegenerative disease linked to the accumulation of α-synuclein (α-syn) in patient neurons. However, it is unclear what the mechanism might be. Here, we demonstrate a novel role for lysosomal exocytosis in clearing intracellular α-syn and show that impairment of this pathway by mutations in the PD-linked gene ATP13A2/PARK9 contributes to α-syn accumulation in human dopaminergic neurons. Importantly, upregulating lysosomal exocytosis by increasing lysosomal Ca2+ levels was sufficient to rescue defective α-syn secretion and accumulation in patient neurons. These studies identify lysosomal exocytosis as a potential therapeutic target in diseases characterized by the accumulation of α-syn, including PD.

Acid ceramidase inhibition ameliorates α-synuclein accumulation upon loss of GBA1 function.

GBA1 encodes the lysosomal enzyme ß-glucocerebrosidase (GCase) which converts glucosylceramide into ceramide and glucose. Mutations in GBA1 lead to Gaucher's disease and are a major risk factor for Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), synucleinopathies characterized by accumulation of intracellular α-synuclein. In this study, we examined whether decreased ceramide that is observed in GCase-deficient cells contributes to α-synuclein accumulation. We demonstrated that deficiency of GCase leads to a reduction of C18-ceramide species and altered intracellular localization of Rab8a, a small GTPase implicated in secretory autophagy, that contributed to impaired secretion of α-synuclein and accumulation of intracellular α-synuclein. This secretory defect was rescued by exogenous C18-ceramide or chemical inhibition of lysosomal enzyme acid ceramidase that converts lysosomal ceramide into sphingosine. Inhibition of acid ceramidase by carmofur resulted in increased ceramide levels and decreased glucosylsphingosine levels in GCase-deficient cells, and also reduced oxidized α-synuclein and levels of ubiquitinated proteins in GBA1-PD patient-derived dopaminergic neurons. Together, these results suggest that decreased ceramide generation via the catabolic lysosomal salvage pathway in GCase mutant cells contributes to α-synuclein accumulation, potentially due to impaired secretory autophagy. We thus propose that acid ceramidase inhibition which restores ceramide levels may be a potential therapeutic strategy to target synucleinopathies linked to GBA1 mutations including PD and DLB.

Perovskite Light-Emitting Diodes with Improved Outcoupling Using a High-Index Contrast Nanoarray.

Organic-inorganic hybrid perovskite light-emitting diodes (PeLEDs) are promising for next-generation optoelectronic devices due to their potential to achieve high color purity, efficiency, and brightness. Although the external quantum efficiency (EQE) of PeLEDs has recently surpassed 20%, various strategies are being pursued to increase EQE further and reduce the EQE gap compared to other LED technologies. A key point to further boost EQE of PeLEDs is linked to the high refractive index of the perovskite emissive layer, leading to optical losses of more than 70% of emitted photons. Here, it is demonstrated that a randomly distributed nanohole array with high-index contrast can effectively enhance outcoupling efficiency in PeLEDs. Based on a comprehensive optical analysis on the perovskite thin film and outcoupling structure, it is confirmed that the nanohole array effectively distributes light into the substrate for improved outcoupling, allowing for 1.64 times higher light extraction. As a result, highly efficient red/near-infrared PeLEDs with a peak EQE of 14.6% are demonstrated.

Printed fabric heater based on Ag nanowire/carbon nanotube composites.

The increasing demand for smart fabrics has inspired extensive research in the field of nanomaterial-based wearable heaters. However, existing stretchable heaters employ polymer substrates, and hence require additional substrate-fabric bonding that can result in high thermal contact resistance. Moreover, currently used stretchable fabric heaters suffer from high sheet resistance and require complex fabrication processes. In addition, conventional fabrication methods do not allow for patternability, thus hindering the fabrication of wearable heaters with diverse designs. Herein, we propose an improved spray coating method well suited for the preparation of patternable heaters on commercial fabrics, combining the structural stability of carbon nanotubes with the high electrical conductivity of Ag nanowires to fabricate a stretchable fabric heater with excellent mechanical (stretchability ≈ 50%) and electrical (sheet resistance ≈ 22 Ω sq-1) properties. The fabricated wearable heater reaches typical operating temperatures of 35 °C-55 °C at a low driving voltage of 3-5 V with a proper surface power density of 26.6-72.2 [Formula: see text] (heater area: [Formula: see text]) and maintains a stable heating temperature for more than 30 h. This heater shows a stable performance even when folded or rolled, thus being well suited for the practical wearable applications.

LONG-TERM PROGNOSTIC FACTORS FOR VISUAL IMPROVEMENT AFTER EPIRETINAL MEMBRANE REMOVAL.

PURPOSE: To identify prognostic factors that may predict the amount of long-term visual improvement after idiopathic epiretinal membrane removal. METHODS: A retrospective study of 114 patients who underwent epiretinal membrane removal was performed. The central foveal thickness, inner retinal layer thickness, inner retinal irregularity index, length of the cone outer segment tip line defect, and length of the ellipsoid zone defect were measured. The optical coherence tomography parameters that were associated with the amount of visual improvement were determined at 24 months postoperatively. RESULTS: Central foveal thickness and inner retinal irregularity index were not associated with best-corrected visual acuity at 24 months (P = 0.227 and P = 0.544, respectively), whereas the lengths of cone outer segment tip line defect and ellipsoid zone defect were associated with worse best-corrected visual acuity at 24 months (P = 0.015 and P < 0.001, respectively). Univariate regression analysis indicated that central foveal thickness and inner retinal irregularity index were associated with visual improvement (P = 0.011 and P < 0.001, respectively). Multivariate regression analysis indicated that inner retinal irregularity index, a marker of the inner retinal deformation, was associated with visual improvement after adjusting for age, gender, and other optical coherence tomography findings (P < 0.001). CONCLUSION: Patients with preoperative inner retinal deformation were found to have significantly improved long-term visual outcomes after epiretinal membrane removal.

Adenosinergic signaling inhibits oxalate transport by human intestinal Caco2-BBE cells through the A2B adenosine receptor.

Most kidney stones (KS) are composed of calcium oxalate, and small increases in urine oxalate affect the stone risk. Intestinal oxalate secretion mediated by anion exchanger SLC26A6 (PAT1) plays a crucial role in limiting net absorption of ingested oxalate, thereby preventing hyperoxaluria and related KS, reflecting the importance of understanding regulation of intestinal oxalate transport. We previously showed that ATP and UTP inhibit oxalate transport by human intestinal Caco2-BBE cells (C2). Since ATP is rapidly degraded to adenosine (ADO), we examined whether intestinal oxalate transport is regulated by ADO. We measured [14C]oxalate uptake in the presence of an outward Cl gradient as an assay of Cl-oxalate exchange activity, ≥49% of which is PAT1-mediated in C2 cells. We found that ADO significantly inhibited oxalate transport by C2 cells, an effect completely blocked by the nonselective ADO receptor antagonist 8- p-sulfophenyltheophylline. ADO also significantly inhibited oxalate efflux by C2 cells, which is important since PAT1 mediates oxalate efflux in vivo. Using pharmacological antagonists and A2B adenosine receptor (A2B AR) siRNA knockdown studies, we observed that ADO inhibits oxalate transport through the A2B AR, phospholipase C, and PKC. ADO inhibits oxalate transport by reducing PAT1 surface expression as shown by biotinylation studies. We conclude that ADO inhibits oxalate transport by lowering PAT1 surface expression in C2 cells through signaling pathways including the A2B AR, PKC, and phospholipase C. Given higher ADO levels and overexpression of the A2B AR in inflammatory bowel disease (IBD), our findings have potential relevance to pathophysiology of IBD-associated hyperoxaluria and related KS.

Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets.

Plasmonic color filters fabricated via oxide-based nanotransfer printing.

Plasmonic filters have recently become a topic of significant interest because they are suitable for a wide range of applications. However, effective fabrication of plasmonic filters remains a challenge. In this paper, we demonstrate a simple method for fabricating plasmonic color filters based on nanotransfer printing (nTP) , using SiO2 as a hard mask for Al etching. nTP was performed on a 100 nm Al layer deposited on a glass wafer substrate with a 10 nm Al layer and a 20 nm SiO2 layer with a nanohole pattern. The 10 nm Al layer and 20 nm SiO2 layers were previously transferred from a polymer stamp prepared to create patterns of subwavelength-sized holes. The plasmonic filters were ultimately fabricated using the SiO2 layer as a hard mask to selectively etch the Al layer. The optical properties of the fabricated plasmonic filters were evaluated using experimental and simulation tools. In addition, we analyzed the results of nTP on the Al and SiO2 films by varying the temperature, pressure, and SiO2-film thickness. We believe that this technique is a promising method for fabricating nanostructures and for widening the scope of practical application of plasmonics because of its high efficiency and cost-effectiveness.

Activation of ß-Glucocerebrosidase Reduces Pathological α-Synuclein and Restores Lysosomal Function in Parkinson's Patient Midbrain Neurons.

UNLABELLED: Parkinson's disease (PD) is characterized by the accumulation of α-synuclein (α-syn) within Lewy body inclusions in the nervous system. There are currently no disease-modifying therapies capable of reducing α-syn inclusions in PD. Recent data has indicated that loss-of-function mutations in the GBA1 gene that encodes lysosomal ß-glucocerebrosidase (GCase) represent an important risk factor for PD, and can lead to α-syn accumulation. Here we use a small-molecule modulator of GCase to determine whether GCase activation within lysosomes can reduce α-syn levels and ameliorate downstream toxicity. Using induced pluripotent stem cell (iPSC)-derived human midbrain dopamine (DA) neurons from synucleinopathy patients with different PD-linked mutations, we find that a non-inhibitory small molecule modulator of GCase specifically enhanced activity within lysosomal compartments. This resulted in reduction of GCase substrates and clearance of pathological α-syn, regardless of the disease causing mutations. Importantly, the reduction of α-syn was sufficient to reverse downstream cellular pathologies induced by α-syn, including perturbations in hydrolase maturation and lysosomal dysfunction. These results indicate that enhancement of a single lysosomal hydrolase, GCase, can effectively reduce α-syn and provide therapeutic benefit in human midbrain neurons. This suggests that GCase activators may prove beneficial as treatments for PD and related synucleinopathies. SIGNIFICANCE STATEMENT: The presence of Lewy body inclusions comprised of fibrillar α-syn within affected regions of PD brain has been firmly documented, however no treatments exist that are capable of clearing Lewy bodies. Here, we used a mechanistic-based approach to examine the effect of GCase activation on α-syn clearance in human midbrain DA models that naturally accumulate α-syn through genetic mutations. Small molecule-mediated activation of GCase was effective at reducing α-syn inclusions in neurons, as well as associated downstream toxicity, demonstrating a therapeutic effect. Our work provides an example of how human iPSC-derived midbrain models could be used for testing potential treatments for neurodegenerative disorders, and identifies GCase as a critical therapeutic convergence point for a wide range of synucleinopathies.

Phase, current, absorbance, and photoluminescence of double and triple metal ion-doped synthetic and salmon DNA thin films.

We fabricated synthetic double-crossover (DX) DNA lattices and natural salmon DNA (SDNA) thin films, doped with 3 combinations of double divalent metal ions (M2+)-doped groups (Co2+-Ni2+, Cu2+-Co2+, and Cu2+-Ni2+) and single combination of a triple M2+-doped group (Cu2+-Ni2+-Co2+) at various concentrations of M2+ ([M2+]). We evaluated the optimum concentration of M2+ ([M2+]O) (the phase of M2+-doped DX DNA lattices changed from crystalline (up to ([M2+]O) to amorphous (above [M2+]O)) and measured the current, absorbance, and photoluminescent characteristics of multiple M2+-doped SDNA thin films. Phase transitions (visualized in phase diagrams theoretically as well as experimentally) from crystalline to amorphous for double (Co2+-Ni2+, Cu2+-Co2+, and Cu2+-Ni2+) and triple (Cu2+-Ni2+-Co2+) dopings occurred between 0.8 mM and 1.0 mM of Ni2+ at a fixed 0.5 mM of Co2+, between 0.6 mM and 0.8 mM of Co2+ at a fixed 3.0 mM of Cu2+, between 0.6 mM and 0.8 mM of Ni2+ at a fixed 3.0 mM of Cu2+, and between 0.6 mM and 0.8 mM of Co2+ at fixed 2.0 mM of Cu2+ and 0.8 mM of Ni2+, respectively. The overall behavior of the current and photoluminescence showed increments as increasing [M2+] up to [M2+]O, then decrements with further increasing [M2+]. On the other hand, absorbance at 260 nm showed the opposite behavior. Multiple M2+-doped DNA thin films can be used in specific devices and sensors with enhanced optoelectric characteristics and tunable multi-functionalities.

Rapid Low-Temperature 3D Integration of Silicon Nanowires on Flexible Substrates.

The vertical integration of 1D nanostructures onto the 2D substrates has the potential to offer significant performance gains to flexible electronic devices due to high integration density, large surface area, and improved light absorption and trapping. A simple, rapid, and low temperature transfer bonding method has been developed for this purpose. Ultrasonic vibration is used to achieve a low temperature bonding within a few seconds, resulting in a polymer-matrix-free, electrically conducting vertical assembly of silicon nanowires (SiNWs) with a graphene/PET substrate. The microscopic structure, and mechanical and electrical characteristics of the interface between the transferred SiNW array and graphene layer are subsequently investigated, revealing that this creates a mechanically robust and electrically Ohmic contact. This newly developed ultrasonic transfer bonding technique is also found to be readily adaptable for diverse substrates of both metal and polymer. It is therefore considered as a valuable technique for integrating 1D vertical nanostructures onto the 2D flexible substrates for flexible photovoltaics, energy storage, and water splitting systems.

A facile patterning of silver nanowires using a magnetic printing method.

Patterning of metal nanowires (NWs) is vital for the fabrication of NW-based, high-performance devices such as sensors, transparent conducting electrodes, and optoelectronics. However, the majority of existing patterning methods require complex and expensive technologies. For this reason, we report for the first time a facile and quick patterning method of silver (Ag) NWs using a magnetic printing method. We successfully demonstrated a patterned AgNW grid structure ona flexible substrate as transparent electrodes. The flexible AgNW grid electrode exhibited optical and electrical properties comparable to those of commercial transparent conducting electrodes.We believe our work will be broadly applicable to other NW-based devices such as sensors,energy storage devices, meta devices, nanoscale electronics, and optoelectronics.