Efficacy of inverted inner limiting membrane flap technique for macular holes of ≤400 µm: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of inverted internal limiting membrane (ILM) flap technique in full-thickness macular holes (MHs) with a size of ≤400 µm compared to the ILM peeling technique. METHODS: Related literatures that compared inverted ILM flap and ILM peeling in MHs ≤ 400 µm were reviewed by searching electronic databases including Pubmed, EMbase, ClinicalTrials.gov, and Cochrane Library up to April 2023. The primary outcome measure was hole closure rate, and the secondary outcome measures were the mean postoperative best-corrected visual acuity (BCVA), retinal sensitivity, and outer status of the retinal layers, including the external limiting membrane and ellipsoid zone. The quality of the articles was assessed according to the revised version of the Cochrane risk-of-bias tool for randomized trials or the Newcastle-Ottawa scale. In the case of heterogeneity, a sensitivity analysis was conducted, and publication bias was visually evaluated using a funnel plot. RESULTS: This review included six studies with 610 eyes for the primary outcome and 385 eyes for the secondary outcomes, which were two randomized control trials and four retrospective studies. Pooled data revealed that the overall MH closure rate was 99.4% in the inverted ILM flap group and 96.2% in the ILM peeling group, without significant difference between the two groups (odds ratio = 3.91; 95% confidence interval, 0.82~18.69; P = 0.09). The inverted ILM flap technique did not have a favorable effect on the BCVA, retinal sensitivity, or recovery of the outer retinal layers. These results were consistent with those of the subgroup analysis of the different follow-up periods. No significant publication bias was observed. CONCLUSION: In eyes with MHs of ≤400 µm, both techniques demonstrated excellent surgical outcomes without significant differences. Therefore, surgical techniques can be selected according to surgeon preferences.

Treatment of aqueous per- and poly-fluoroalkyl substances: A review of biochar adsorbent preparation methods.

Per- and poly-fluoroalkyl substances (PFAS) are synthetic chemicals widely used in everyday products, causing elevated concentrations in drinking water and posing a global challenge. While adsorption methods are commonly employed for PFAS removal, the substantial cost and environmental footprint of commercial adsorbents highlight the need for more cost-effective alternatives. Additionally, existing adsorbents exhibit limited effectiveness, particularly against diverse PFAS types, such as short-chain PFAS, necessitating modifications to enhance adsorption capacity. Biochar can be considered a cost-effective and eco-friendly alternative to conventional adsorbents. With abundant feedstocks and favorable physicochemical properties, biochar shows significant potential to be applied as an adsorbent for removing contaminants from water. Despite its effectiveness in adsorbing different inorganic and organic contaminants from water environments, some factors restrict its effective application for PFAS adsorption. These factors are related to the biochar properties, and characteristics of PFAS, as well as water chemistry. Therefore, some modifications have been introduced to overcome these limitations and improve biochar's adsorption capacity. This review explores the preparation conditions, including the pyrolysis process, activation, and modification techniques applied to biochar to enhance its adsorption capacity for different types of PFAS. It addresses critical questions about the adsorption performance of biochar and its composites, mechanisms governing PFAS adsorption, challenges, and future perspectives in this field. The surge in research on biochar for PFAS adsorption indicates a growing interest, making this timely review a valuable resource for future research and an in-depth exploration of biochar's potential in PFAS remediation.

Data Preprocessing and Augmentation Improved Visual Field Prediction of Recurrent Neural Network with Multi-Central Datasets.

INTRODUCTION: The purpose of this study was to determine whether data preprocessing and augmentation could improve visual field (VF) prediction of recurrent neural network (RNN) with multi-central datasets. METHODS: This retrospective study collected data from five glaucoma services between June 2004 and January 2021. From an initial dataset of 331,691 VFs, we considered reliable VF tests with fixed intervals. Since the VF monitoring interval is very variable, we applied data augmentation using multiple sets of data for patients with more than eight VFs. We obtained 5,430 VFs from 463 patients and 13,747 VFs from 1,076 patients by setting the fixed test interval to 365 ± 60 days (D = 365) and 180 ± 60 days (D = 180), respectively. Five consecutive VFs were provided to the constructed RNN as input and the 6th VF was compared with the output of the RNN. The performance of the periodic RNN (D = 365) was compared to that of an aperiodic RNN. The performance of the RNN with 6 long- and short-term memory (LSTM) cells (D = 180) was compared with that of the RNN with 5-LSTM cells. To compare the prediction performance, the root mean square error (RMSE) and mean absolute error (MAE) of the total deviation value (TDV) were calculated as accuracy metrics. RESULTS: The performance of the periodic model (D = 365) improved significantly over aperiodic model. Overall prediction error (MAE) was 2.56 ± 0.46 dB versus 3.26 ± 0.41 dB (periodic vs. aperiodic) (p < 0.001). A higher perimetric frequency was better for predicting future VF. The overall prediction error (RMSE) was 3.15 ± 2.29 dB versus 3.42 ± 2.25 dB (D = 180 vs. D = 365). Increasing the number of input VFs improved the performance of VF prediction in D = 180 periodic model (3.15 ± 2.29 dB vs. 3.18 ± 2.34 dB, p < 0.001). The 6-LSTM in the D = 180 periodic model was more robust to worsening of VF reliability and disease severity. The prediction accuracy worsened as the false-negative rate increased and the mean deviation decreased. CONCLUSION: Data preprocessing with augmentation improved the VF prediction of the RNN model using multi-center datasets. The periodic RNN model predicted the future VF significantly better than the aperiodic RNN model.

Carbon Dioxide-Mediated Desalination.

Conventional desalination membrane technologies, although offer portable drinking water, are still energy-intensive processes. This paper proposes a potentially new approach for performing water desalination and purification by utilizing the reversible interaction of carbon dioxide (CO2) with nucleophilic amines─reminiscent of the Solvay process. Based on our model studies with small molecules, CO2-responsive amphiphilic insoluble diamines were prepared, characterized, and applied in the formation of soda and ammonium chloride upon exposure to ambient CO2 (1 atm), thus removing chloride ions from model and real seawater. This ion-exchange process and separation of chloride from the aqueous phase are spontaneous in the presence of CO2 without the need for external energy sources. We demonstrate a flow system to envisage energy-efficient CO2-mediated desalination and simultaneous carbon capture and sequestration.

Anomaly Detection Based on Time Series Data of Hydraulic Accumulator.

Although hydraulic accumulators play a vital role in the hydraulic system, they face the challenges of being broken by continuous abnormal pulsating pressure which occurs due to the malfunction of hydraulic systems. Hence, this study develops anomaly detection algorithms to detect abnormalities of pulsating pressure for hydraulic accumulators. A digital pressure sensor was installed in a hydraulic accumulator to acquire the pulsating pressure data. Six anomaly detection algorithms were developed based on the acquired data. A threshold averaging algorithm over a period based on the averaged maximum/minimum thresholds detected anomalies 2.5 h before the hydraulic accumulator failure. In the support vector machine (SVM) and XGBoost model that distinguish normal and abnormal pulsating pressure data, the SVM model had an accuracy of 0.8571 on the test set and the XGBoost model had an accuracy of 0.8857. In a convolutional neural network (CNN) and CNN autoencoder model trained with normal and abnormal pulsating pressure images, the CNN model had an accuracy of 0.9714, and the CNN autoencoder model correctly detected the 8 abnormal images out of 11 abnormal images. The long short-term memory (LSTM) autoencoder model detected 36 abnormal data points in the test set.

Perampanel as First Add-On Therapy in Patients with Focal-Onset Seizures in the FAME Trial: Post hoc Analyses of Efficacy and Safety Related to Maintenance Dose and Background Antiepileptic Drug Therapy.

Background and Purpose: FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel. Methods: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs). Results: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p<0.001) and when added to first- versus second-line ASM monotherapy (83.5% vs. 33.3%; p=0.013). By concomitant background ASM and perampanel maintenance dose, 50% responder rates were 100% for perampanel 4 mg/day added to carbamazepine, oxcarbazepine, lamotrigine, or valproic acid, and 85% when added to levetiracetam. Add-on perampanel improved 75% and seizure-free responder rates, and median percent changes from baseline seizure frequency per 28 days. Perampanel was well tolerated when added to ASM monotherapy, with dizziness being the most common TEAE. Conclusions: Post hoc analyses of FAME provide supportive data for the use of perampanel as an effective and well-tolerated first add-on treatment to a broad spectrum of ASM monotherapies in patients with FOS.

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response.

Background and Purpose: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel. Methods: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed. Results: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%). Conclusions: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

ROS Signaling Mediates Directional Cell Elongation and Somatic Cell Fusion in the Red Alga Griffithsia monilis.

In many filamentous red algae, cells that die from physical damage are replaced through somatic fusion of repair cells formed from adjacent cells. We visualized ROS generation in repair cells of Giriffthsia monilis using DCFH-DA staining and examined the expression of the genes involved in wound healing using quantitative PCR. Repair cells elongate along the H2O2 gradient, meet at each other's tips where the H2O2 concentration is highest, and undergo somatic fusion. No wound response occurred with ascorbic acid treatment. Conversely, H2O2 treatment induced many repair cells, leading to multiple somatic cell fusions. Diphenylene iodonium (DPI) or caffeine treatment reversibly inhibited ROS production in repair cells and blocked the progression of the wound response suggesting that ROS and calcium signaling are involved in the process. Four G. monilis homologues of NADPH-oxidase (GmRBOHs) were identified. The expression of GmRBOHs was upregulated upon injury, peaking 1 h post injury, and decreasing to initial levels when repair cells began to elongate. Our results suggest that ROS generated upon cell injury activates Ca2+ channels and upregulates the expression of GmRBOHs, and that H2O2 generated from repair cells mediates induced repair cell elongation leading to somatic cell fusion and filament repair.

Carbon dioxide enhances sulphur-selective conjugate addition reactions.

Sulphur-selective conjugate addition reactions play a central role in synthetic chemistry and chemical biology. A general tool for conjugate addition reactions should provide high selectivity in the presence of competing nucleophilic functional groups, namely nitrogen nucleophiles. We report CO2-mediated chemoselective S-Michael addition reactions where CO2 can reversibly control the reaction pHs, thus providing practical reaction conditions. The increased chemoselectivity for sulphur-alkylation products was ascribed to CO2 as a temporary and traceless protecting group for nitrogen nucleophiles, while CO2 efficiently provide higher conversion and selectivity sulphur nucleophiles on peptides and human serum albumin (HSA) with various electrophiles. This method offers simple reaction conditions for cysteine modification reactions when high chemoselectivity is required.

The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma.

BACKGROUND: The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. METHODS: The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. RESULTS: In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e-6 and 1.55e-7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e-12 and 2.55e-6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e-17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e-8). CONCLUSIONS: The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.

An ETS-NOCV-based computational strategies for the characterization of concerted transition states involving CO2.

Due to the presence of both a slightly acidic carbon and a slightly basic oxygen, carbon dioxide is often involved in concerted transition states (TSs) with two (or more) different molecular events interlaced in the same step. The possibility of isolating and quantitatively evaluating each molecular event would be important to characterize and understand the reaction mechanism in depth. This could be done, in principle, by measuring the relevant distances in the optimized TS, but often distances are not accurate enough, especially in the presence of many simultaneous processes. Here, we have applied the Extended Transition State-Natural Orbital for Chemical Valence-method (ETS-NOCV), also in combination with the Activation Strain Model (ASM) and Energy Decomposition Analysis (EDA), to separate and quantify these molecular events at the TS of both organometallic and organic reactions. For the former, we chose the decomposition of formic acid to CO2 by an iridium catalyst, and for the latter, a CO2 -mediated transamidation and its chemical variations (hydro- and aminolysis of an ester) as case studies. We demonstrate that the one-to-one mapping between the "molecular events" and the ETS-NOCV components is maintained along the entire lowest energy path connecting reactants and products around the TS, thus enabling a detailed picture on the relative importance of each interacting component. The methodology proposed here provides valuable insights into the effect of different chemical substituents on the reaction mechanism and promises to be generally applicable for any concerted TSs.

Bioinspired Fatty Acid Amide-Based Slippery Oleogels for Shear-Stable Lubrication.

Liquid-repellent technology is an efficient means of energy-saving and biofouling avoidance. However, liquid-repellent surfaces suffer from inefficient lubricant retention under shear flow and fouling problem in marine environment. Here, the authors demonstrate a fatty acid amide (FAA)-based oleogel for stable and sustainable lubrication in marine environment. The lubrication management of marine creatures is emulated in synthetic oleogels by incorporating solid (FAA) and liquid lubricants into the molecular meshes of polymeric networks, with the nature-derived solid lubricant providing multifunctional synergistic effects with liquid oil molecules for slippery property and remarkable anti-biofouling. The lubricant-confining gel achieves shear-stable lubricity with efficient oil management. The oleogel provides continued lubrication without biofouling for approximately 4 months in marine field tests. The gel design provides a new paradigm for sustainable and shear-stable lubrication in marine environment.

Hydrogen peroxide signalling mediates fertilization and post-fertilization development in the red alga Bostrychia moritziana.

Reactive oxygen species (ROS) signalling has a multitude of roles in cellular processes throughout biology. We hypothesized that red algal fertilization may offer an interesting model to study ROS-mediated signalling, as the stages of fertilization are complex and unique. We detected the localization of ROS production microscopically and monitored the expression of three homologues of NADPH oxidase in reproductive cells during fertilization. ROS were instantaneously produced by spermatia (sperm) when they attached to female trichogynes, diffused across the cell membrane in the form of H2O2, and triggered ROS generation in the carpogonium (egg) as well as carpogonial branch cells which are not in direct contact with spermatia. The expression of NADPH oxidase homologues, RESPIRATORY BURST OXIDASE HOMOLOGUES (BmRBOHs), began to be up-regulated in the female plant upon gamete binding, peaking during the fertilization process and descending back to their original level after fertilization. Pre-treatment with diphenylene iodonium or caffeine blocked gene expression as well as H2O2 production. Post-fertilization development was also inhibited when the redox state of the plants was perturbed with H2O2 at any time before or after the fertilization. Our results suggest that H2O2 acts as an auto-propagating signalling molecule, possibly through Ca2+ channel activation, and regulates gene expression in fertilization as well as post-fertilization development in red algae.

Differences in the eyelid and buccal microbiome between open-angle glaucoma and uveitic glaucoma.

PURPOSE: Microbiomes have immunoregulatory functions and may be involved in the pathophysiology of eye diseases. However, the effects of microbiomes on uveitic glaucoma (UG) and open-angle glaucoma (OAG) have not been sufficiently investigated. This study analysed differences in eyelid and buccal microbiomes between UG and OAG using metagenomic technology. METHODS: Eyelid and buccal specimens were collected from 34 UG and 62 OAG patients. The taxonomic composition of the microbiome was determined via 16S rRNA gene sequencing, operational taxonomic unit analysis and diversity analysis. Differential gene expression analysis (DEG) and principal component analyses (PCoA) determined taxon differences between the microbiomes of the UG and OAG patients. Subgroup analysis according to age and baseline IOP was performed. RESULTS: There was no significant difference in alpha-diversity between the microbiomes of UG and OAG patients. Further, PCoA revealed no differences in eyelid microbiome between the UG and OAG groups, but significant differences were found in buccal microbiome between the groups, especially in a subgroup of OAG patients with normal IOP. DEG analysis of the eyelid microbiome revealed various taxa differences, including the enrichment of Rhodococcus in UG samples over OAG samples. Taxa such as Lactobacillus and Proteus were significantly depleted (q-value = 9.98e-6 and q-value = 1.38 × 10-4 , respectively) in the buccal microbiome of UG patients, whereas Enterococcus was enriched (q-value = 5.26e-5 ). CONCLUSIONS: This study showed that the buccal microbiome in UG differs from that in OAG; reduced Lactobacillus was observed in UG. These results suggest that apart than OAG, microbiome composition may be a factor in the pathogenesis of UG.

Evaluation of persistence and healthcare utilization in patients treated with anti-seizure medications as add-on therapy: A nationwide cohort study in South Korea.

OBJECTIVE: To compare medication adherence and healthcare utilization among patients who were treated with anti-seizure medications (ASMs) as first add-on to monotherapy for epilepsy using the national health insurance claims data. METHODS: A retrospective observational cohort study was conducted using the Korean National Health Insurance claims data. Patients who received ASM as first add-on to monotherapy during January 2017 to February 2018 were included. The selected patients were followed up for 12 months to evaluate persistence, adherence, and healthcare resource utilization. RESULTS: In total, 4277 patients who received ASM as first add-on to monotherapy for epilepsy were enrolled. The mean treatment duration of add-on ASM was 296.6 ±â€¯108.6 days during the 1-year follow-up period and 64.3% of the total population were persistent on the add-on ASM at 365 days from the index date. The mean medication possession ratio (MPR) was 90.3 ±â€¯23.7 and the proportion of adherent patients with ≥80% MPR was 79.3%. Lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), and perampanel (PER) groups showed significantly higher persistence and adherence than carbamazepine (CBZ), topiramate (TPM), and valproate (VAL) groups during the 1-year follow-up period. Significant differences in length of stays, total hospitalization cost, outpatient visit cost, and emergency cost were shown between ASM groups and LTG, LEV, OXC, and PER showed relatively low utilization and cost. CONCLUSIONS: Better adherence was observed in LTG, LEV, OXC, and PER groups than in CBZ, TPM, and VAL groups. Healthcare utilization and related costs showed significant difference between ASM groups.

Long-term efficacy and safety of perampanel as a first add-on therapy in patients with focal epilepsy: Three-year extension study.

PURPOSE: We investigated the long-term efficacy and safety of perampanel as a first add-on therapy in patients with focal epilepsy. METHODS: This retrospective study represented the 3-year extension phase of a multicenter, open-label, phase 4, prospective study of perampanel as a first add-on therapy in patients with focal epilepsy. Seizure and safety outcomes were assessed annually from the start of the extension study, and the retention rate was calculated from the start of perampanel exposure in the original study. RESULTS: The 50% responder and seizure freedom rates were 84.8% and 58.7%, respectively, during the third year and 71.7% and 32.6%, respectively, during the entire 3-year period of the extension study. The 1-, 2-, and 3-year retention rates were 62.5%, 53.1%, and 52.1%, respectively. Efficacies were higher in patients that were aged >55 years, male, and receiving ≤4 mg of perampanel. Perampanel was generally well tolerated; 47.3% of patients experienced at least one adverse event during the 3 years of extension (46 adverse events (AEs) in 35 patients). The most common AEs were dizziness (33.8%), somnolence (5.4%), anger (4.1%), and irritability (4.1%). AEs were resolved with perampanel dose reduction or discontinuation in 10 (13.5%) and 12 (16.2%) patients, respectively. CONCLUSION: Long-term treatment with perampanel as a first add-on therapy did not raise new safety signals in patients with focal epilepsy. Especially at low perampanel doses (≤4 mg/day), sustained improvement in seizure control was achieved, which could potentially avoid adverse drug reactions.

A CO2-Catalyzed Transamidation Reaction.

Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2 as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2 atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2 in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2.

Controlled Metal-Support Interactions in Au/CeO2-Mg(OH)2 Catalysts Activating the Direct Oxidative Esterification of Methacrolein with Methanol to Methyl Methacrylate.

The strong metal-support interaction (SMSI) between the three components in Au/CeO2-Mg(OH)2 can be controlled by the relative composition of CeO2 and Mg(OH)2 and by the calcination temperature for the direct oxidative esterification of methacrolein (MACR) with methanol to methyl methacrylate (MMA). The composition ratio of CeO2 and Mg(OH)2 in the catalyst affects the catalytic performance dramatically. An Au/CeO2 catalyst without Mg(OH)2 esterified MACR to a hemiacetal species without MMA production, which confirmed that Mg(OH)2 is a prerequisite for successful oxidative esterification. When Au/Mg(OH)2 was used without CeO2, the direct oxidative esterification of MACR was successful and produced MMA, the desired product. However, the MMA selectivity was much lower (72.5%) than that with Au/CeO2-Mg(OH)2 catalysts, which have an MMA selectivity of 93.9-99.8%, depending on the relative composition of CeO2 and Mg(OH)2. In addition, depending on the calcination temperature, the crystallinity of the CeO2-Mg(OH)2 and the surface acidity/basicity can be remarkably changed. Consequently, the Au-nanoparticle-supported catalysts exhibited different MACR conversions and MMA selectivities. The catalytic behavior can be explained by the different metal-support interactions between the three components depending on the composition ratio of CeO2 and Mg(OH)2 and the calcination temperature. These differences were evidenced by X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature-programmed desorption. The present study provides new insights into the design of SMSI-induced supported metal catalysts for the development of multifunctional heterogeneous catalysts.

Cooperative Asymmetric Cation-Binding Catalysis.

Asymmetric cation-binding catalysis in principle enables the use of (alkali) metal salts, otherwise insoluble in organic solvents, as reagents and effectors in enantioselective reactions. However, this concept has been a formidable challenge due to the difficulties associated with creating a highly organized chiral environment for cations and anions simultaneously. Over the last four decades, various chiral crown ethers have been developed as cation-binding phase-transfer catalysts and examined in asymmetric catalysis. However, the limited ability of chiral crown ethers to generate soluble reactive anions in a confined chiral cage offers a restricted reaction scope and unsatisfactory chirality induction. To address the constraints of monofunctional chiral crown ethers as cation-binding catalysts, it is therefore desirable to develop a cooperative cation-binding catalyst possessing secondary binding sites for anions, which enables the generation of a reactive anion within a chiral cage of a catalyst. This account summarizes our design, development, and applications of chiral BINOL-based oligoethylene glycols (oligoEGs) as a new type of bifunctional cation-binding catalyst. We initially found that achiral oligoEGs were efficient promoters in nucleophilic fluorination with potassium fluoride. Thereby, we hypothesized that, by breaking the closed cyclic ether unit of chiral crown ethers, the free terminal -OH groups could activate the electrophiles by hydrogen bonding whereas the ether oxygens could act as the Lewis base to coordinate metal ions, thus generating soluble anions in a confined chiral cage. This hypothesis was realized by synthesizing a series of chiral variants of oligoEGs by connecting two 3,3'-disubstituted-BINOL units with glycol linkers. Readily available BINOL-based chiral oligoEGs enabled numerous asymmetric transformations out of the reach of chiral monofunctional crown ether catalysts. We have demonstrated that this new type of bifunctional cation-binding catalysts can generate a soluble fluoride anion from alkali metal fluorides, which can be a versatile chiral promoter for diverse asymmetric catalytic reactions, kinetic resolution (selectivity factor of up to ∼2300), asymmetric protonation, Mannich reactions, tandem cyclization reactions, and the isomerization of allylic alcohols and hemithioacetals. We have also successfully utilized our chiral oligoEG catalysts along with alkali metal salts of carbon- and heteroatom-based nucleophiles, respectively, for asymmetric Strecker reactions and the asymmetric synthesis of chiral aminals. The power of our cooperative cation-binding catalysis was exemplified by kinetic resolution reactions of secondary alcohols, achieving highly enantioselective catalysis with only <1 ppm loading of an organocatalyst with high TOFs (up to ∼1300 h-1 at 1 ppm catalyst loading). The broadness and generality of our cooperative asymmetric cation-binding catalysis can be ascribed, in a similar fashion, to active-site architectures of enzymes using allosteric interactions, highly confined chiral cages formed by the incorporation of alkali metal salts in the catalyst polyether chain backbone, and the cooperative activation of reacting partners by hydrogen-bonding and ion-ion interactions. Confining reactive components in such a chiral binding pocket leads to enhanced reactivity and efficient transfer of the stereochemical information.

Efficacy and safety of newly developed preservative-free latanoprost 0.005% eye drops versus preserved latanoprost 0.005% in open angle glaucoma and ocular hypertension: 12-week results of a randomized, multicenter, controlled phase III trial.

AIM: To evaluate the therapeutic efficacy, safety and tolerability of newly developed preservative-free (PF) latanoprost generic [TJO-002] and compare it with benzalkonium chloride (BAK)-preserved latanoprost [Xalatan®] in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: Included patients were aged ≥19y with POAG/OHT. After a washout period, patients with IOP 21-35 mm Hg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, 144 patients with POAG and OHT participated in this study. Subjects were randomly assigned either PF latanoprost (74 eyes) or BAK-preserved latanoprost (70 eyes). All subjects were examined at 4, 8, and 12wk after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 5 p.m. and compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the masked investigators who measured IOP. RESULTS: Both groups showed a statistically significant decrease of average diurnal IOP at 12wk compared to baseline (-7.21±3.10 mm Hg in the PF latanoprost group and -7.02±3.17 mm Hg in the BAK latanoprost group, both P<0.0001). There was no statistically significant diurnal IOP variation between the groups. In terms of tolerability, pruritus, burning/stinging, and sticky eye sensation, severity was significantly lower in the PF latanoprost group than in the BAK latanoprost group (P<0.05). CONCLUSION: PF latanoprost has at least similar efficacy in terms of IOP reduction and better tolerability compared with BAK latanoprost.