Electrochemically Stable Ligands of ZnO Electron-Transporting Layers for Quantum-Dot Light-Emitting Diodes.

Thin films of ZnO nanocrystals are actively pursued as electron-transporting layers (ETLs) in quantum-dot light-emitting diodes (QLEDs). However, the developments of ZnO-based ETLs are highly engineering oriented and the design of ZnO-based ETLs remains empirical. Here, we identified a previously overlooked efficiency-loss channel associated with the ZnO-based ETLs: i.e., interfacial exciton quenching induced by surface-bound ethanol. Accordingly, we developed a general surface-treatment procedure to replace the redox-active surface-bound ethanol with electrochemically inert alkali carboxylates. Characterization results show that the surface treatment procedure does not change other key properties of the ETLs, such as the conductance and work function. Our single-variable experimental design unambiguously demonstrates that improving the electrochemical stabilities of the ZnO ETLs leads to QLEDs with a higher efficiency and longer operational lifetime. Our work provides a crucial guideline to design ZnO-based ETLs for optoelectronic devices.

Long-Term Outcomes of High-Dose Conbercept Treatment for Myopic Choroidal Neovascularization and Idiopathic Choroidal Neovascularization.

INTRODUCTION: The aim of the study was to report 2-year outcomes of intravitreal injection of high-dose conbercept (1 mg 2 + PRN scheme) for subjects with myopic choroidal neovascularization (mCNV) and idiopathic choroidal neovascularization (iCNV) by optical coherence tomography angiography follow-up. METHODS: A total of 38 subjects (38 eyes) were enrolled in this retrospective study, which were divided into group A (mCNV, 20 subjects, 20 eyes) and group B (iCNV, 18 subjects, 18 eyes). All subjects received 1.0 mg of conbercept intravitreally at diagnosis and again 35 days later. Additional conbercept injection was administered upon findings of decreased best-corrected visual acuity (BCVA); metamorphosis aggravation, macular hemorrhage, or edema; increased central retinal thickness (CRT); or leakage observed by fluorescein angiography. The BCVA, CRT, and CNV areas of the two groups were evaluated at baseline and at 1, 2, 4, 6, 12, and 24 months after surgery. RESULTS: The BCVA of group A improved from 0.31 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001), while in group B the corresponding improvement was from 0.33 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001). Visual acuity improved in 17 subjects in group A and 15 in group B, while it remained stable in 3 subjects in each of groups A and B. CRT decreased from 311.83 ± 30.95 µm in group A and 351.17 ± 37.09 µm in group B preoperation to 229.56 ± 5.75 µm and 227.67 ± 4.98 µm at 24-month follow-up, respectively (p < 0.001 in groups A and B). Metamorphopsia was improved in subjects in groups A and B. CNV had disappeared in the two groups at the last postoperative visit. The BCVA, CRT, and CNV areas showed no statistical differences between the two groups at 6-, 12-, and 24-month follow-up (p > 0.05). CONCLUSION: Intravitreal injection of conbercept (1 mg 2 + PRN scheme) is effective for treating patients with mCNV or iCNV, which can improve and stabilize vision as well as dramatically alleviate metamorphopsia.

Effects of TYROBP Deficiency on Neuroinflammation of a Alzheimer's Disease Mouse Model Carrying a PSEN1 p.G378E Mutation.

Objective To study the effects of TYRO protein kinase-binding protein (TYROBP) deficiency on learning behavior, glia activation and pro-inflammatory cycokines, and Tau phosphorylation of a new Alzheimer's disease (AD) mouse model carrying a PSEN1 p.G378E mutation.Methods A new AD mouse model carrying PSEN1 p.G378E mutation was built based on our previously found AD family which might be ascribed to the PSEN1 mutation, and then crossed with TYROBP deficient mice to produce the heterozygous hybrid mice (PSEN1G378E/WT; Tyrobp+/-) and the homozygous hybrid mice (PSEN1G378E/G378E; Tyrobp-/-). Water maze test was used to detect spatial learning and memory ability of mice. After the mice were sacrificed, the hippocampus was excised for further analysis. Immunofluorescence was used to identify the cell that expresses TYROBP and the number of microglia and astrocyte. Western blot was used to detect the expression levels of Tau and phosphorylated Tau (p-Tau), and ELISA to measure the levels of pro-inflammatory cytokines. Results Our results showed that TYROBP specifically expressed in the microglia of mouse hippocampus. Absence of TYROBP in PSEN1G378E mutation mouse model prevented the deterioration of learning behavior, decreased the numbers of microglia and astrocytes, and the levels of interleukin-6, interleukin-1ß and tumor necrosis factor-α in the hippocampus (all P < 0.05). The ratios of AT8/Tau5, PHF1/Tau5, pT181/Tau5, pT231/Tau5 and p-ERK/ERK were all higher in homozygous hybrid mice (PSEN1G378E/G378E; Tyrobp-/- mice) compared with PSEN1G378E/G378E mice (all P < 0.05). Conclusions TYROBP deficiency might play a protective role in the modulation of neuroinflammation of AD. However, the relationship between neuroinflammation processes involving microglia and astrocyte activation, and release of pro-inflammatory cytokines, and p-Tau pathology needs further study.

Guillain-Barré syndrome in Eastern China: A study of 595 patients.

BACKGROUND AND PURPOSE: This study aimed to investigate geographical differences in the clinical features of Guillain-Barré syndrome (GBS) between patients from our region in Eastern China and patients from other areas. METHODS: A total of 595 patients fulfilling the diagnostic criteria ​for GBS or its variants were included from two large hospitals located in Eastern China. Data collection included demographics, antecedent events, clinical presentation and signs, electrophysiological subtypes, treatment, complications during hospitalization, clinical severity at nadir, and outcome at 12 months, and these data were compared to data from a study conducted in Southern China and the Europe/Americas section of the International GBS Outcome Study. RESULTS: The median (interquartile range) age of patients was 50 (36-61) years, the ratio of men to women was 1.2, and 49% of patients had antecedent events. Patients in our region of Eastern China had pure motor predominant GBS (158/340, 46%) and 30% (103/340) had complications during hospitalization. Patients aged over 60 years had a lower frequency of antecedent infections and single, axonal subtypes, but higher disability scores at entry, nadir, and 12 months. When compared with the Europe/Americas data, our patients had a lower frequency of antecedent infection (46% vs. 63%), cranial nerve involvement (43% vs. 49%), sensory deficits (45% vs. 69%), pain (19% vs. 57%) and mechanical ventilation (11% vs. 17%), but a higher frequency of axonal subtype (35% vs. 6%). There was a higher frequency of patients with antecedent gastroenteritis (16% vs. 8%), mechanical ventilation (11% vs. 8%) and axonal subtypes (35% vs. 19%) in our region in Eastern China than in Southern China. CONCLUSIONS: Patients with GBS in Eastern China showed significant clinical heterogeneity and differences when compared to other geographic areas.

Health-related quality of life after first-ever acute ischemic stroke: associations with cardiovascular health metrics.

PURPOSE: To investigate the associations between cardiovascular health (CVH) metrics and health-related quality of life (HRQL) among patients with ischemic stroke in China, and further explore the role of physical and cognitive function in their associations. METHODS: This hospital-based study included 1714 patients with first-ever acute ischemic stroke (age ≥ 40 years; 36.7% women) who were admitted to two university hospitals in Shandong, China. We collected information on seven CVH metrics (smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting blood glucose) through interviews, clinical examinations, and laboratory tests. EQ-5D-3L was used to assess HRQL. Cognitive and physical functioning was assessed by the Montreal Cognitive Assessment test and Barthel index, respectively. Data were analyzed using the general linear regression models. RESULTS: The average score (SD) was 0.746 (0.23) for HRQL index and 72.7 (15.8) for self-rated health. Optimal levels of four individual CVH metric components (diet, physical activity, blood pressure, and blood glucose) and a higher composite CVH score were significantly associated with a greater HRQL index and better self-rated health (p < 0.05 for all). Physical dependence and cognitive impairment were associated with a lower HRQL index and poorer self-rated health status (p < 0.001). Furthermore, the relationships between CVH metrics and HRQL index varied by functional status, such that their associations were statistically significant only among people who had physical dependence or cognitive impairment. CONCLUSION: Achieving a better cardiovascular health profile is associated with better quality of life among ischemic stroke survivors, primarily in those with physical or cognitive impairment.

Bruceine D elevates Nrf2 activation to restrain Parkinson's disease in mice through suppressing oxidative stress and inflammatory response.

Parkinson's disease (PD) is neurodegenerative disease, featured by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Development of effective therapeutic drugs for PD is necessary. In this study, we investigated the potential of Bruceine D (BD) during PD progression. After establishment of PD mouse models, we found that BD markedly improved the motor function of mice and alleviated chemically induced dopaminergic neuron loss of tyrosine hydroxylase (TH) in the SNpc area. BD treatments markedly repressed the neuroinflammation in SNpc by restricting nuclear factor κB (NF-κB) activation, accompanied with the reduced activity of astrocytes and microglial. BD also improved the antioxidant system in MPTP-challenged mice, as proved by the up-regulated superoxide dismutase (SOD) and glutathione (GSH), and down-regulated malondialdehyde (MDA) in SNpc and striatum (STR). The anti-oxidant effects of BD were regulated by the activation of nuclear factor E2-related factor 2 (Nrf2) signaling, contributing to the expression of Nrf2 down-streaming signals such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione cysteine ligase modulatory subunit (GCLM). In MPP+-challenged mouse neurons, BD exhibited cytoprotective effects by improving the Nrf2-meditated antioxidant system and abolished the MPP+-triggered inflammatory response through hindering the activation of the NF-κB signal. The pharmacokinetic parameters and organ distribution findings demonstrated that BD showed a brain tissue targeting function. Moreover, both in vivo and in vitro analysis indicated that BD had few side effects. Collectively, results here demonstrated that BD was effective for the inhibition of dopaminergic neuronal loss and PD progression by activating Nrf2 without toxicity.

Co-occurrence of Moyamoya syndrome and Kartagener syndrome caused by the mutation of DNAH5 and DNAH11: a case report.

BACKGROUND: Kartagener syndrome is an autosomal recessive inherited disorder of primary ciliary dyskinesia. Moyamoya syndrome refers to a moyamoya angiopathy associated with other neurological and/or extra-neurological symptoms, or due to a well identified acquired or inherited cause. We herein reported a case of a 48-year-old woman who was favored the diagnosis of Kartagener syndrome and moyamoya syndrome. The whole genome sequencing and bioinformatics analysis showed a homozygotic nonsense mutation in the dynein, axonemal, heavy chain (DNAH) 5 gene, and heterozygotic missense mutation in the DNAH11 gene. This is the first report of the co-occurrence of the two rare diseases. CASE PRESENTATION: A case of a 48-year-old woman was presented with hemiplegia and slurred speech. The magnetic resonance imaging of the brain confirmed acute cerebral infarction in the right basal ganglia region, semi-oval center, insular lobe, and frontal parietal lobe. The electrocardiogram showed inverted "P" waves in L1 and AVL on left-sided chest leads and computed tomography scan of the chest showed bronchiectasis changes, cardiac shadow and apex on the right side, and situs inversus of aortic arch position. The digital subtraction angiography showed inversion of the aortic arch, and bilateral internal carotid arteries are occluded from the ophthalmic segment. The clinical, radiological, and laboratory findings made the diagnosis of Kartagener syndrome and moyamoya syndrome. The whole genome sequencing and bioinformatics analysis showed a homozygotic nonsense mutation in DNAH5 gene, and heterozygotic missense mutation in the DNAH11 gene. CONCLUSION: The combined mutation of DNAH5 and DNAH11 may lead to the overlapping dysfunction of motile and nonmotile cilia, which contribute to the co-occurrence of Kartagener syndrome and moyamoya syndrome. Our report deserves further confirm by more case reports.

Profiling of differentially expressed circular RNAs in peripheral blood mononuclear cells from Alzheimer's disease patients.

Expression of circular RNA (circRNA), a class of noncoding RNAs that regulates gene expression, is altered in Alzheimer's disease. This study profiled differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from five patients with Alzheimer's disease compared to healthy controls using circRNA microarrays. We identified a total of 4060 differentially expressed circRNAs (1990 upregulated and 2070 downregulated) in Alzheimer's disease patients. Among these circRNAs, 10 randomly selected circRNAs were verified using qRT-PCR. The top 10 upregulated and downregulated circRNAs were used to predict their target miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed circRNAs were strongly associated with inflammation, metabolism, and immune responses, which are all risk factors for Alzheimer's disease. The circRNA-miRNA-mRNA network was most involved in the MAPK, mTOR, AMPK, and WNT signaling pathways in Alzheimer's disease. In conclusion, the current study demonstrated the importance of circRNAs in Alzheimer's disease development. Future studies will evaluate some of these circRNAs as biomarkers for early disease detection and to develop therapeutic strategies to clinically control Alzheimer's disease progression.

Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

Human Umbilical Cord Wharton's Jelly Derived Mesenchymal Stromal Cells May Attenuate Sarcopenia in Aged Mice Induced by Hindlimb Suspension.

BACKGROUND Since the use of human umbilical cord Wharton's Jelly derived mesenchymal stromal cells (hWJ-MSCs) to treat sarcopenia has not been explored, we studied the effects of hWJ-MSCs in aged male C57BL/6J mice with sarcopenia induced by hindlimb suspension, and explored the potential mechanism. MATERIAL AND METHODS Hindlimb suspension was used to induce sarcopenia in 24-month-old C57BL/6J mice and green fluorescent protein-tagged hWJ-MSCs and controls were transplanted into mice via tail vein or local intramuscular injection. After hWJ-MSC transplantation, changes in whole body muscle strength and endurance, gastrocnemius muscle weight and myofiber cross-sectional area (CSA) were studied. Proliferation of skeletal muscle stem cell, apoptosis, and chronic inflammation were also investigated. RESULTS We demonstrated that whole body muscle strength and endurance, gastrocnemius muscle mass, and CSA were significantly increased in hWJ-MSC-transplanted mice than in controls (P<0.05). In hWJ-MSC-transplanted mice, apoptotic myonuclei was reduced, and BrdU and Pax-7 expression indices of gastrocnemius muscles were increased (P<0.05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated, and IL-4 and IL-10 were upregulated (P<0.05). CONCLUSIONS hWJ-MSCs may ameliorate sarcopenia in aged male C57BL/6J mice induced by hindlimb suspension, and this may be via activation of resident skeletal muscle satellite cells, reduction of apoptosis, and less chronic inflammation.

Comparative study of microRNA profiling in one Chinese Family with PSEN1 G378E mutation.

MicroRNAs are not widely studied in familial Alzheimer's disease cases, whether the microRNA profilings in familial Alzheimer's disease patients are similar to the sporadic AD patients is not known. This study aims to investigate the differential expression of microRNAs (miRNAs) associated with early-onset familial Alzheimer's disease (EO-FAD) in a Chinese family. We performed the gene mutation analysis in a family clinically diagnosed of EO-FAD. Micro-arrays were used to profile the miRNAs in cerebrospinal fluid of 2 affected members, 2 unaffected carriers and 2 mutation negative controls. The clinical presentation confirmed the EO-FAD diagnosis, and a recurrent mutation of the PSEN1 p.G378E was found in the family. The result showed that in the miRNAs expression profile, a total of 166 miRNAs were up-regulated and 3 miRNAs were down-regulated in the affected individuals compared with mutation negative individuals. But after Benjamini Hochberg FDR correction, only 25 miRNAs were significantly up-regulated and no miRNA was down-regulated, the levels of miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly. Compared with mutation negative controls, 21 miRNAs were up-regulated and 18 microRNAs were down-regulated in the unaffected mutation carriers, after Benjamini Hochberg FDR correction, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. And there was no difference between the affected members and unaffected mutation carriers. GO database showed that the top biological processes affected by the predicted target genes are nucleic acid binding transcription factor activity and transcription factor activity (sequence-specific DNA binding) (GO:0001071 and GO:0003700). The result of KEGG pathways showed 64 pathways were implicated in the regulatory network. The present study identified the miRNA profiling of Chinese siblings with G378E mutation in the PSEN1. Compared with mutation negative controls, the levels of 25 miRNAs including miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly in the affected members, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. Our study showed the microRNA profilings in the cases of a EO-FAD family with PSEN1 p.G378E mutation, but because of the individuals in the family was small, the results in other types of EO-FAD still need further studied.

Vinpocetine Inhibited the CpG Oligodeoxynucleotide-induced Immune Response in Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism. Our data showed that vinpocetine significantly downregulated the expression of CD40, CD80, and CD86 on pDCs and increased the expression of translocator protein (TSPO), the specific receptor of vinpocetine, in pDCs. Vinpocetine significantly inhibited the Toll-like receptor 9 signaling pathway and reduced the secretion of related cytokines in pDCs through TSPO. Furthermore, viability of pDCs was significantly promoted by vinpocetine. These findings imply that vinpocetine serves as an immunomodulatory agent for pDCs and may be applied for the treatment of pDCs-related autoimmune diseases.

Interactions between four gene polymorphisms and their association with patients with Parkinson's disease in a Chinese Han population.

The four previously reported Parkinson's disease (PD)-related single-nucleotide polymorphisms (SNPs) - rs1775143, rs823114, rs2071746 and rs62063857 - have rarely been studied in Chinese Han populations. To examine the association between these SNPs and PD, we conducted a case-control study of 158 patients with PD and 210 controls. All participants were Chinese Han from Northern China. With covariate adjustment for clinical characteristics, logistic regression analysis revealed no differences in genotype or allele frequencies for the four SNPs. Stratified by age of disease onset, sex, smoking status, duration of disease, baseline UPDRS, Hoehn-Yahr Stage, PD subtypes, scores of Hamilton anxiety scale, Hamilton depression scale and activity of daily living, all of the p values did not remain significant after Bonferroni correction. However, the haplotype rs1775143T-rs823114G-rs2071746T-rs62063857A was associated with increased risk of developing PD (p = 0.003, OR = 456.88, 95% CI: 27.40-7619.75) in our case-control sample set. The haplotype rs1775143T-rs823114G-rs2071746T was also associated with increased risk of developing PD (p = 0.003, OR = 338.43, 95% CI: 20.68-5538.27). Although the haplotype rs1775143T-rs823114G-rs62063857A was associated with increased risk of PD (p = 0.03), the 95% CI was 0.993-22.469. Our data demonstrate that although specific SNPs were not related with PD patients, certain haplotypes were associated with increased risk for PD in the Chinese Han population. These results provide further evidence that the etiology of PD is multifactorial, although the underling mechanism needs further study.

Shelf-Stable Green and Blue Quantum Dot Light-Emitting Diodes with High Efficiencies.

Quantum dot light-emitting diodes (QLEDs) are promising electroluminescent devices for next-generation display and solid-state lighting technologies. Achieving shelf-stable and high-performance QLEDs is crucial for their practical applications. However, the successful demonstration of shelf-stable QLEDs with high efficiencies is limited to red devices. Here, we developed a solution-based amine ligand exchange strategy to passivate the surfaces of optical ZnO (O-ZnO) nanocrystals, leading to suppressed exciton quenching at the green and blue QD/oxide interface. Furthermore, we designed new bilayered oxide electron-transporting layers consisting of amine-modified O-ZnO/conductive ZnO. This design simultaneously offers suppressed interfacial exciton quenching and sufficient electron transport in the green and blue QLEDs, resulting in shelf-stable green and blue devices with high efficiencies. Our devices exhibit neglectable changes in external quantum efficiencies (maximum external quantum efficiencies of 22.4% for green and 14.3% for blue) after storage for 270 days. Our work represents a step forward in the practical applications of QLED technology.

Suppression of GSK-3ß activation by M-cadherin protects myoblasts against mitochondria-associated apoptosis during myogenic differentiation.

Apoptosis occurs concurrently with differentiation of muscle progenitor cells (MPCs) before they fuse to form myotubes. Dysregulated apoptosis in MPCs contributes to the low regeneration capability in aged muscle and decreases the survival rate of donor cells in stem cell-based therapies for muscular dystrophies. This study investigated the role of the M-cadherin/PI3K/Akt/GSK-3ß signaling pathway in regulating apoptosis during differentiation of MPCs. Disruption of M-cadherin-dependent cell-cell adhesion by M-cadherin RNA interference in confluent C2C12 myoblasts sensitized the cells to mitochondria-associated intrinsic apoptosis induced by cell confluence or serum starvation. Further investigation of this pathway revealed that M-cadherin-mediated signaling suppressed GSK-3ß activation by enhancing the PI3K/AKT-dependent inhibitory phosphorylation of Ser9 in GSK-3ß. Overexpression of wild-type GSK-3ß in confluent C2C12 myoblasts exacerbated the apoptosis, whereas chemical inhibition of GSK-3ß using TDZD-8, or forced expression of constitutively active Akt (myrAkt), or a kinase-deficient GSK-3ß mutant [GSK-3ß(K85R)], attenuated apoptosis and rescued the impaired myogenic differentiation that is caused by M-cadherin RNA interference. These data suggest that M-cadherin-mediated signaling prevents acceleration of mitochondria-associated intrinsic apoptosis in MPCs by suppressing GSK-3ß activation during myogenic differentiation.

High­dose aflibercept injection has striking effects on myopic choroidal neovascularization.

The aim of the present study was to evaluate the 1-year outcomes of a high-dose aflibercept injection [4 mg 2+ pro re nata (PRN) scheme] for individuals with myopic choroidal neovascularization (mCNV) through optical coherence tomography (OCT) follow-ups. A total of 16 consecutive patients (7 males and 9 females; sixteen eyes) with mCNV were enrolled in this retrospective study. The mean age was 30.5±3.35 years and mean spherical equivalent was -7.31±0.90 D. Subjects received 4 mg aflibercept intravitreal injection on the day of diagnosis and 35 days later. Further injections of aflibercept were required when the following were detected by OCT and fluorescein angiography: i) Decrease in best corrected visual acuity (BCVA); ii) aggravation of metamorphopsia; iii) macular oedema; iv) macular haemorrhage; v) increase in retinal thickness; and vi) leakage. Ophthalmic examination and OCT were performed at the baseline, as well as at 1, 2, 4, 6, 8, 10 and 12 months after the initial aflibercept injection. BCVA and central retinal thickness (CRT) were evaluated at each follow-up. The results showed that the vision of all subjects improved following the aflibercept intravitreal injection. The mean BCVA improved from 0.35±0.15 logarithm of the minimal angle of resolution (logMAR) at the baseline to 0.12±0.05 logMAR at final follow-up (P<0.05). A reduction in metamorphopsia was observed and the mean CRT was reduced from 345.38±34.69 µm of pre-treatment levels to 222.75±8.98 µm at the last postoperative visit (P<0.05). The mean number of injections in the present study was 2.13±0.5. Out of all patients, 13 received two injections and 3 subjects received three injections. The mean follow-up was 13.41±1.17 months. Based on the outcomes, it was found that an intravitreal injection of high-dose aflibercept (4 mg 2+PRN scheme) is effective for vision improvement and stabilization. In addition, it also significantly alleviated metamorphopsia and reduced the CRT in patients treated with mCNV. During the follow-up, the eyesight of the patients was stable.

Highly Efficient Light-Emitting Diodes Based on Self-Assembled Colloidal Quantum Wells.

Nanocrystal-based light-emitting diodes (Nc-LEDs) have immense potential for next-generation high-definition displays and lighting applications. They offer numerous advantages, such as low cost, high luminous efficiency, narrow emission, and long lifetime. However, the external quantum efficiency (EQE) of Nc-LEDs, typically employing isotropic nanocrystals, is limited by the out-coupling factor. Here efficient, bright, and long lifetime red Nc-LEDs based on anisotropic nanocrystals of colloidal quantum wells (CQWs) are demonstrated. Through modification of the substrate's surface properties and control of the interactions among CQWs, a self-assembled layer with an exceptionally high distribution of in-plane transitions dipole moment of 95%, resulting in an out-coupling factor of 37% is successfully spin-coated. The devices exhibit a remarkable peak EQE of 26.9%, accompanied by a maximum brightness of 55 754 cd m-2 and a long operational lifetime (T95 @100 cd m-2 ) over 15 000 h. These achievements represent a significant advancement compared to previous studies on Nc-LEDs incorporating anisotropic nanocrystals. The work is expected to provide a general self-assembly strategy for enhancing the light extraction efficiency of Nc-LEDs based on anisotropic nanocrystals.

Automatic segmentation of hyperreflective dots via focal priors and visual saliency.

PURPOSE: Hyperreflective dots (HRDs) can be observed in spectral domain optical coherence tomography (SD-OCT), which can provide a sensitive marker in the treatment decision process. Quantitative analyses of HRDs are the key to make appropriate decisions on observation, treatment, and retreatment. The purpose of this study is to automatically and accurately segment HRDs in SD-OCT B-scans with diabetic retinopathy (DR). METHODS: The authors propose an automatic segmentation algorithm of HRDs via focal priors and visual saliency. The algorithm is divided into three stages: segmentation of retinal layers, calculation of the multiscale local contrast saliency map, and adaptive threshold segmentation. First, a method based on improved graph search is used to segment retinal layers to obtain the region of interest (ROI) and the reflectivity estimation of the retinal pigment epithelium (RPE) layer; then, the multiscale local contrast saliency map is obtained by using a local contrast measure, which measures the dissimilarity between the current pixels and corresponding neighborhoods; finally, an adaptive threshold is applied to segment HRDs. RESULTS: Experimental results on 20 SD-OCT B-scans demonstrate that our method is effective for HRDs segmentation. The average dice similarity coefficient (DSC) and detection accuracy are 71.12% and 85.07%, respectively. CONCLUSIONS: The proposed method can accurately segment HRDs in SD-OCT B-scans with DR and outperforms current state-of-the-art methods. Our method can provide reliable HRDs segmentation to assist ophthalmologists in clinical diagnosis, treatment, disease monitoring, and progression.

Downregulation of m6A Methyltransferase in the Hippocampus of Tyrobp -/- Mice and Implications for Learning and Memory Deficits.

Loss-of-function mutations in the gene that encodes TYRO protein kinase-binding protein (TYROBP) cause Nasu-Hakola disease, a heritable disease resembling Alzheimer's disease (AD). Methylation of N6 methyl-adenosine (m6A) in mRNA plays essential roles in learning and memory. Aberrant m6A methylation has been detected in AD patients and animal models. In the present study, Tyrobp-/- mice showed learning and memory deficits in the Morris water maze, which worsened with age. Tyrobp-/- mice also showed elevated levels of total tau, Ser202/Thr205-phosphorylated tau and amyloid ß in the hippocampus and cerebrocortex, which worsened with aging. The m6A methyltransferase components METTL3, METTL14, and WTAP were downregulated in Tyrobp-/- mice, while expression of demethylases that remove the m6A modification (e.g., FTO and ALKBH5) were unaltered. Methylated RNA immunoprecipitation sequencing identified 498 m6A peaks that were upregulated in Tyrobp-/- mice, and 312 m6A peaks that were downregulated. Bioinformatic analysis suggested that most of these m6A peaks occur in sequences near stop codons and 3'-untranslated regions. These findings suggest an association between m6A RNA methylation and pathological TYROBP deficiency.

CdSe/CdSeS Nanoplatelet Light-Emitting Diodes with Ultrapure Green Color and High External Quantum Efficiency.

Colloidal II-VI group nanoplatelets (NPLs) possess ultranarrow emission line widths, for which they have great promise in achieving the purest display color in solution-processed light-emitting diodes (LEDs). Red NPL-LEDs have shown extremely saturated red color with high efficiency, while the green and blue ones lag far behind. Herein, we report green NPL-LEDs with the purest color in accordance with the Rec. 2020 standard and the peak external quantum efficiency (EQE) of 9.78%. By carefully controlling the aspect ratio, capping ligands, and purifications of CdSe/CdSeS core/alloyed-crown NPLs, NPL films with excellent flatness and unity photoluminescence quantum yields (PLQYs) are realized, laying a solid foundation for improving LED performance. Furthermore, via tuning the carrier injection balance, the record-high EQE for green NPL-LEDs is achieved. The electroluminescence (EL) exhibits an extremely saturated green color with the Commission Internationale de L'Eclairage (CIE) coordinates of (0.163 0.786), which demonstrates their great potential in applications of ultrahigh-definition display technology. Our findings would help to further improve the performance of all NPL-LEDs.