Photostimulated Pyrothermoelectric Coupling in Two-Dimensional Tin Monoselenide Enabling Zero-Biased Multimodal Transducers.

Despite the advancement of the Internet of Things (IoT) and portable devices, the development of zero-biased sensing systems for the dual detection of light and gases remains a challenge. As an emerging technology, direct energy conversion driven by intriguing physical properties of two-dimensional (2D) materials can be realized in nanodevices or a zero-biased integrated system. In this study, we unprecedentedly attempted to exploit the photostimulated pyrothermoelectric coupling of two-dimensional SnSe for use in zero-biased multimodal transducers for the dual detection of light and gases. We synthesized homogeneous, large-area 6 in SnSe multilayers via a rational synthetic route based on the thermal decomposition of a solution-processed single-source precursor. Zero-biased SnSe transducers for the dual monitoring of light and gases were realized by exploiting the synergistic coupling of the photostimulated pyroelectric and thermoelectric effects of SnSe. The extracted photoresponsivity at 532 nm and NO2 gas responsivity of the SnSe-based transducers corresponded to 1.07 × 10-6 A/W and 13263.6% at 0 V, respectively. To bring universal applicability of the zero-biased SnSe transducers, the wide operation bandwidth photoelectrical properties (visible to NIR) and dynamic current responses toward two NO2/NH3 gases were systematically evaluated.

GPR41 and GPR43: From development to metabolic regulation.

G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host's intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host's intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions.

Artificial Q-Grader: Machine Learning-Enabled Intelligent Olfactory and Gustatory Sensing System.

Portable and personalized artificial intelligence (AI)-driven sensors mimicking human olfactory and gustatory systems have immense potential for the large-scale deployment and autonomous monitoring systems of Internet of Things (IoT) devices. In this study, an artificial Q-grader comprising surface-engineered zinc oxide (ZnO) thin films is developed as the artificial nose, tongue, and AI-based statistical data analysis as the artificial brain for identifying both aroma and flavor chemicals in coffee beans. A poly(vinylidene fluoride-co-hexafluoropropylene)/ZnO thin film transistor (TFT)-based liquid sensor is the artificial tongue, and an Au, Ag, or Pd nanoparticles/ZnO nanohybrid gas sensor is the artificial nose. In order to classify the flavor of coffee beans (acetic acid (sourness), ethyl butyrate and 2-furanmethanol (sweetness), caffeine (bitterness)) and the origin of coffee beans (Papua New Guinea, Brazil, Ethiopia, and Colombia-decaffeine), rational combination of TFT transfer and dynamic response curves capture the liquids and gases-dependent electrical transport behavior and principal component analysis (PCA)-assisted machine learning (ML) is implemented. A PCA-assisted ML model distinguished the four target flavors with >92% prediction accuracy. ML-based regression model predicts the flavor chemical concentrations with >99% accuracy. Also, the classification model successfully distinguished four different types of coffee-bean with 100% accuracy.

Wafer-Scale Atomic Assembly for 2D Multinary Transition Metal Dichalcogenides for Visible and NIR Photodetection.

The tunable properties of 2D transition-metal dichalcogenide (TMDs) materials are extensively investigated for high-performance and wavelength-tunable optoelectronic applications. However, the precise modification of large-scale systems for practical optoelectronic applications remains a challenge. In this study, a wafer-scale atomic assembly process to produce 2D multinary (binary, ternary, and quaternary) TMDs for broadband photodetection is demonstrated. The large-area growth of homogeneous MoS2, Ni0.06Mo0.26S0.68, and Ni0.1Mo0.9S1.79Se0.21 is carried out using a succinct coating of the single-source precursor and subsequent thermal decomposition combined with thermal evaporation of the chalcogen powder. The optoelectrical properties of the multinary TMDs are dependent on the combination of heteroatoms. The maximum photoresponsivity of the MoS2-, Ni0.06Mo0.26S0.68-, and Ni0.1Mo0.9S1.79Se0.21-based photodetectors is 3.51 × 10-4, 1.48, and 0.9 A W-1 for 532 nm and 0.063, 0.42, and 1.4 A W-1 for 1064 nm, respectively. The devices exhibited excellent photoelectrical properties, which is highly beneficial for visible and near-infrared (NIR) photodetection.

Fusion Length Requiring Spinopelvic Fixation in Lumbosacral Fusion with Anterior Column Support at L5-S1: Assessment of Fusion Status Using Computed Tomography.

Background: The lumbosacral (LS) junction has a higher nonunion rate than other lumbar segments, especially in long-level fusion. Nonunion at L5-S1 would result in low back pain, spinal imbalance, and poor surgical outcomes. Although anterior column support at L5-S1 has been recommended to prevent nonunion in long-level LS fusion, fusion length requiring additional spinopelvic fixation (SPF) in LS fusion with anterior column support at L5-S1 has not been evaluated thoroughly. This study aimed to determine the number of fused levels requiring SPF in LS fusion with anterior column support at L5-S1 by assessing the interbody fusion status using computed tomography (CT) depending on the fusion length. Methods: Patients who underwent instrumented LS fusion with L5-S1 interbody fusion without additional augmentation and CT > 1 year postoperatively were included. The fusion rates were assessed based on the number of fused segments. Patients were divided into two groups depending on the L5-S1 interbody fusion status: those with union vs. those with nonunion. Binary logistic regression analyses were performed to identify risk factors for LS junctional nonunion. Results: Fusion rates of L5-S1 interbody fusion were 94.9%, 90.3%, 80.0%, 50.0%, 52.6%, and 43.5% for fusion of 1, 2, 3, 4, 5, and ≥ 6 levels, respectively. The number of spinal levels fused ≥ 4 (p < 0.001), low preoperative bone mineral density (BMD; adjusted odds ratio [aOR], 0.667; p = 0.035), and postoperative pelvic incidence (PI) - lumbar lordosis (LL) mismatch (aOR, 1.034; p = 0.040) were identified as significant risk factors for nonunion of L5-S1 interbody fusion according to the multivariate logistic regression analysis. Conclusions: Exhibiting ≥ 4 fused spinal levels, low preoperative BMD, and large postoperative PI-LL mismatch were identified as independent risk factors for nonunion of anterior column support at L5-S1 in LS fusion without additional fixation. Therefore, SPF should be considered in LS fusion extending to or above L2 to prevent LS junctional nonunion.

Effective prediction finite element model of pull-out capacity for cast-in-place anchor in high strain rate effects.

Cast-in-place anchors are being increasingly used in many applications including building construction, bridge, and power plants. The anchorage to concrete systems are subjected to tensile, shear and combined loads from a variety of loading circumstances including static, dynamic, and shock loading. Despite extensive studies on these systems, reliable numerical models for predicting the behavior of these anchors are still limited. Therefore, this paper investigated the tensile behavior of cast-in-place anchorage to concrete systems, to propose an effective model for reproducing anchorage behavior using finite element (FE) methods. Experiments and code-based models for the anchorage system in tension were used to evaluate the numerical models for cast-in-place anchors in concrete, and the most suitable model, with advantages in accuracy and saving analysis time, was chosen. Finally, the FE model was used to study the tensile capacity and related dynamic increase factor for various strain rates, anchor diameters, and embedment depths.

Comparison of patient experiences and clinical outcomes between an illuminated chopper and a conventional chopper under a surgical microscope.

PURPOSE: To compare patient experiences and cooperation and the clinical outcomes illuminated chopper vs conventional chopper during cataract surgery. SETTING: 4 tertiary institutions in Korea. DESIGN: Prospective, randomized, paired-eye, controlled pilot study. METHODS: 152 eyes of 76 patients who underwent bilateral cataract surgeries were enrolled in this study. The surgical method was randomly assigned to each patient's eye (1 eye using the illuminated chopper with a light source and the other using the conventional chopper under the microscope light). Patient suffering scores (the degree of strong light perception, glare, inability to fixate, anxiety, discomfort, and fear) from 0 to 10 (10 being the most severe level); cooperation score from 0 to 3 (3 being the best cooperation); operating time; and corneal endothelial cell density (ECD) preoperatively and postoperatively were compared between the 2 groups. RESULTS: The mean patient suffering score of all 6 parameters in the iChopper group was significantly smaller than those in the control group (all P < .05). The mean patient cooperation score of the iChopper group (2.3 ± 0.8) was significantly greater than that of the control (1.6 ± 0.9; P < .001). There was no significant difference in the mean operating time and corneal ECD at each visit between the groups, albeit the mean corneal ECD was significantly decreased from baseline to 1 month after cataract surgery in both groups. CONCLUSIONS: Phacoemulsification using the illuminated chopper provides less glare and anxiety and better cooperation during cataract surgery without increasing the operating time and damaging corneal endothelium compared with the conventional chopper.

Gαi -coupled GPR41 activation increases Ca2+ influx in C2C12 cells and shows a therapeutic effect in diabetic animals.

OBJECTIVE: This study aimed to investigate the possible mechanisms by which orphan G protein-coupled receptor GPR41 activation enhances glucose uptake into C2C12 myotubes using a GPR41-selective agonist, AR420626, and to examine the ability of this agent to improve insulin sensitivity and glucose homeostasis in vivo. METHODS: Basal and insulin-stimulated glucose uptake and glucose transporter 4 translocations were measured in C2C12 myotubes. Ca2+ influx into cells was measured and GPR41-mediated signaling by AR420626 was examined. An oral glucose tolerance test was performed, and plasma insulin levels were measured in streptozotocin-treated or high-fat diet-fed diabetic mice. The glycogen content was measured in skeletal muscle tissue. RESULTS: AR420626 increased basal and insulin-stimulated glucose uptake, which was reduced by pertussis toxin, an inhibitor of Gαi -mediated signaling, and treatment with small interfering RNA for GPR41 (siGPR41). AR420626 increased intracellular Ca2+ influx and phosphorylated Ca2+ /calmodulin-dependent protein kinase type II, cyclic AMP-responsive element-binding protein, and mitogen-activated protein kinase (p38) in C2C12 myotubes, which were inhibited by treating with pertussis toxin, amlodipine (Ca2+ channel blocker), and siGPR41. AR420626 increased plasma insulin levels and skeletal muscle glycogen content and improved glucose tolerance in streptozotocin- and high-fat diet-induced diabetic mouse models. CONCLUSIONS: GPR41 activation with AR420626 increased glucose uptake mediated by Ca2+ signaling via GPR41, improving diabetes mellitus.

The Effects of Bond-Slip Laws on the Debonding Failure and Behavior of Flexural Strengthened RC Slabs in Hybrid FRP Retrofit Systems.

The hybrid retrofit system using FRP and concrete overlay applied on the top of slabs has proven effective in strengthening and overcoming logistical constraints, compared with conventional strengthening techniques using externally bonded composite materials to the underside of the slabs. Nevertheless, the performance of retrofitted slabs is governed by debonding failure due to the low bond strength between CFRP and concrete overlay. Thus, this study investigates the behavior of flexural strengthened slabs with FRP retrofit systems and the effect of bond-slip laws on debonding failure. Firstly, two full-scale RC slabs with and without a retrofit system were tested in a four-point bending setup as the control specimens. Then, the same retrofitted slab was simulated by utilizing the commercial program ABAQUS. A sensitivity analysis was conducted to consider the influence of bond-slip laws to predict the failure mechanism of the retrofitted slabs based on load-deflection relationships. The results showed that the strengthened slab enhanced the load-carrying capacity by 59%, stiffness by 111%, and toughness by 29%. The initial stiffness of 0.1K0 and maximum shear stress of 0.13τmax, compared with the corresponding values of Neubauer's and Rostasy's bond-slip law, can be used to simulate the global response of the retrofitted slab validated by experiment results.

Incorporation of Silica Particles Attached to Nylon 66 Electrospun Nanofibers with Cement.

In this study, a modified version of electrospun nylon 66 nanofibers by silica particles were blended into ordinary Portland cement to investigate the microstructure and some mechanical properties of cementitious material. The addition of silica into the nanofibers improved the tensile and compressive properties of the hardened cement pastes. The observations from the mechanical strength tests showed an increase of 41%, 33% and 65% in tensile strength, compressive strength, and toughness, respectively, when modifying the cement pastes with the proposed nanofibers. The observations from scanning electron microscopy and transmission electron microscopy showed the morphology and microstructure of the fibers as well as their behaviors inside the cement matrix. Additionally, X-ray diffraction and thermal gravimetric analysis clarified the occurrence of the extra pozzolanic reaction, as well as the calcium hydroxide consumption by the attached silica inside the cement matrix. Finally, the observations from this study showed the successful fabrication of the modified nanofibers and the feasibility of improving the tensile and compressive behaviors of cement pastes using the proposed electrospun nanofibers.

Comparison of a preservative-free nonsteroidal anti-inflammatory drug and preservative-free corticosteroid after uneventful cataract surgery: multicenter, randomized, evaluator-blinded clinical trial.

PURPOSE: To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp indicators. SETTING: 11 eye centers in South Korea. DESIGN: Randomized prospective multicenter study with a blinded evaluator. METHOD: In 125 (250 eyes) patients who underwent cataract surgery, bromfenac sodium hydrate 0.1% (NSAID group) was applied twice a day in 1 eye, whereas the other eye was treated with fluorometholone 0.1% (steroid group), 4 times a day for 4 weeks postoperatively. The primary efficacy outcome was the presence of anterior chamber cells and flare at 1 week postoperatively. Anterior chamber cells and flare at 4 to 8 weeks, corrected distance visual acuity, central corneal thickness, conjunctival hyperemia, dry eye parameters, foveal thickness, and ocular and visual discomfort were evaluated as secondary outcomes. RESULTS: At week 1, residual anterior chamber inflammation was not statistically significantly different between the groups (-1.03 ± 1.27 vs -0.95 ± 1.24, P = .4850). However, the NSAID group recovered from conjunctival hyperemia more rapidly than the steroid group (0.30 ± 0.52 vs 0.44 ± 0.81, P = .0144 at week 1). The increase in central corneal thickness in the NSAID group was less than that in the steroid group 1 week postoperatively (7.87 ± 22.46 vs 29.47 ± 46.60 µm, P < .0001). The change in foveal thickness in the NSAID group was significantly less than that in the steroid group (18.11 ± 68.19 vs 22.25 ± 42.37 µm, P = .0002). Lower levels of postoperative ocular and visual discomfort were reported in the NSAID group than in the steroid group under treatment. CONCLUSIONS: Preservative-free bromfenac was as effective as preservative-free fluorometholone eyedrops in anterior chamber inflammation control and showed better signs and symptoms after cataract surgery.

A Design Method to Induce Ductile Failure of Flexural Strengthened One-Way RC Slabs.

Strengthening existing reinforced concrete (RC) slabs using externally bonded materials is increasingly popular due to its adaptability and versatility. Nevertheless, ductility reduction of the rehabilitated flexural members with these materials can lead to brittle shear failure. Therefore, a new approach for strengthening is necessary. This paper presents a methodology to induce ductile failure of flexural strengthened one-way RC slabs. Ultimate failure loads can be considered to develop the proposed design methodology. Different failure modes corresponding to ultimate failure loads for RC slabs are addressed. Flexural and shear failure regions of RC slabs can be established by considering the failure modes. The end span of the concrete slab is shown for a case study, and numerical examples are solved to prove the essentiality of this methodology.

Cataract Surgery Practice in the Republic of Korea: A Survey of the Korean Society of Cataract and Refractive Surgery 2020.

PURPOSE: To describe current cataract surgery practice patterns and trends among Korean ophthalmologists. METHODS: A survey was conducted among members of the Korean Society of Cataract and Refractive Surgery in October 2020. Of the 998 questionnaires, 262 (26.3%) were received for analysis. Data were analyzed using descriptive statistics and compared with those of previous surveys. RESULTS: The largest percentage of respondents (39%) had <5 years of practical experience, and 40% had >11 years of practical experience. The average, median, and mode monthly volumes of cataract surgeries performed by the Korean Society of Cataract and Refractive Surgery members were 31, 20, and 10 cases, respectively. Topical anesthesia was administered by 85% of the respondents. For intraocular lens (IOL) calculations, 96% of the respondents used optical biometry. The proportion of surgeons providing femtosecond laser-assisted cataract surgery increased significantly from 5% in 2018 to 29% in 2020. This increase was accompanied by an increase in the multifocal IOLs. Those who implant multifocal IOL for >10% of their cases increased from 16% (2018) to 29% (2020). Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 76% of the respondents. Most respondents (70%) prescribed these anti-inflammatory drugs for 4 weeks. CONCLUSIONS: This survey provided a comprehensive update on current cataract surgery practice in the Republic of Korea. The results highlighted the increasing use of premium IOLs, femtosecond laser-assisted cataract surgery, optical biometry, and topical anesthesia to better meet the patients' needs.

Rosuvastatin Inhibits the Apoptosis of Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells by Inhibiting p38 via Autophagy.

The secretion of platelet-derived growth factors (PDGFs) into vascular smooth muscle cells (VSMCs) induced by specific stimuli, such as oxidized low-density lipoprotein (LDL) cholesterol, initially increases the proliferation and migration of VSMCs, and continuous stimulation leads to VSMC apoptosis, resulting in the formation of atheroma. Autophagy suppresses VSMC apoptosis, and statins can activate autophagy. Thus, this study aimed to investigate the mechanism of the autophagy-mediated vasoprotective activity of rosuvastatin, one of the most potent statins, in VSMCs continuously stimulated with PDGF-BB, a PDGF isoform, at a high concentration (100 ng/ml) to induce phenotypic switching of VSMC. Rosuvastatin inhibited apoptosis in a concentration-dependent manner by reducing cleaved caspase-3 and interleukin-1ß (IL-1ß) levels and reduced intracellular reactive oxygen species (ROS) levels in PDGF-stimulated VSMCs. It also inhibited PDGF-induced p38 phosphorylation and increased the expression of microtubule-associated protein light chain 3 (LC3) and the conversion of LC3-I to LC3-II in PDGF-stimulated VSMCs. The ability of rosuvastatin to inhibit apoptosis and p38 phosphorylation was suppressed by treatment with 3-methyladenine (an autophagy inhibitor) but promoted by rapamycin (an autophagy activator) treatment. SB203580, a p38 inhibitor, reduced the PDGF-induced increase in intracellular ROS levels and inhibited the formation of cleaved caspase-3, indicating the suppression of apoptosis. In carotid ligation model mice, rosuvastatin decreased the thickness and area of the intima and increased the area of the lumen. In conclusion, our observations suggest that rosuvastatin inhibits p38 phosphorylation through autophagy and subsequently reduces intracellular ROS levels, leading to its vasoprotective activity. SIGNIFICANCE STATEMENT: This study shows the mechanism responsible for the vasoprotective activity of rosuvastatin in vascular smooth muscle cells under prolonged platelet-derived growth factor stimulation. Rosuvastatin inhibits p38 activation through autophagy, thereby suppressing intracellular reactive oxygen species levels, leading to the inhibition of apoptosis and reductions in the intima thickness and area. Overall, these results suggest that rosuvastatin can be used as a novel treatment to manage chronic vascular diseases such as atherosclerosis.

Regulation of autophagy by controlling Erk1/2 and mTOR for platelet-derived growth factor-BB-mediated vascular smooth muscle cell phenotype shift.

AIMS: Vascular smooth muscle cell (VSMC) phenotype shift is involved in the pathophysiology of vascular injury or platelet-derived growth factor (PDGF)-induced abnormal proliferation and migration of VSMCs. We aimed to investigate the underlying mechanism involved in PDGF-mediated signaling pathways and autophagy regulation followed by VSMC phenotype shift. MAIN METHODS: The proliferation, migration and apoptosis of cultured rat aortic VSMCs were measured, and cells undergoing phenotype shift and autophagy were examined. Specific inhibitors for target proteins in signaling pathways were applied to clarify their roles in regulating cell functions. KEY FINDINGS: PDGF-BB stimulation initiated autophagy activation and synthetic phenotype transition by decreasing α-smooth muscle-actin (SMA), calponin and myosin heavy chain (MHC) and increasing osteopontin (OPN) expression. However, U0126, a potent extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, decreased PDGF-BB-induced LC3 expression, while rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), increased it. Furthermore, U0126 decreased the expresseion of autophagy-related genes (Atgs) such as beclin-1, Atg7, Atg5, and Atg12-Atg5 complex, indicating that Erk1/2 is a regulator of PDGF-BB-induced VSMC autophagy. Regardless of autophagy inhibition by U0126 or activation by rapamycin, the PDGF-BB-induced decrease in SMA, calponin and MHC and increase in OPN expression were inhibited. Furthermore, PDGF-BB-stimulated VSMC proliferation, migration and proliferating cell nuclear antigen (PCNA) expression were inhibited by U0126 and rapamycin. SIGNIFICANCE: These findings suggest that PDGF-BB-induced autophagy is strongly regulated by Erk1/2, an mTOR-independent pathway, and any approach for targeting autophagy modulation is a potential therapeutic strategy for addressing abnormal VSMC proliferation and migration.

Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling.

Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G0/G1 phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.

Therapeutic effects of celecoxib polymeric systems in rat models of inflammation and adjuvant-induced rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA), an autoimmune inflammatory disease, is rapidly increasing in aging societies. In the current study, celecoxib (CXB) micelles were developed to improve the oral absorption and anti-inflammatory effects of CXB in cell studies and λ-carrageenan rat models, and to enhance the therapeutic effects of CXB on RA in complete Freund's adjuvant (CFA)-induced RA rat models. Moreover, CXB micelles and previously developed solid dispersion (SD6) formulations were evaluated. The physical properties of optimal CXB micelles (M3), such as crystallinity, thermal properties, and intramolecular interactions, were altered. Compared with the commercial product (Celebrex®), the M3 and SD6 formulations showed significantly improved anti-inflammatory effects in terms of nitric oxide reduction, 1.5-fold and 2.2-fold, respectively, at the cellular level. The relative bioavailability (BA) of the M3 and SD6 formulations was also significantly improved as oral bioavailability (167.2% and 219.8% respectively), compared with that of Celebrex®. In particular, M3 and SD6 significantly reduced inflammation and edema volume relative to Celebrex® in CFA-induced RA rat models. Moreover, both M3 and SD6 effectively suppressed CFA-induced pro-inflammatory cytokines (TNF-α and IL-1ß) in rat splenic tissues. In conclusion, polymeric systems improved the solubility, relative BA (%) and anti-inflammatory effects of CXB. Thus, CXB polymeric systems show potential as therapeutic agents against inflammation and RA and may need to be tested at the clinical level.

Retraction Note: Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

An amendment to this paper has been published and can be accessed via the original article.

Efficacy of Topical Cyclosporine Nanoemulsion 0.05% Compared with Topical Cyclosporine Emulsion 0.05% and Diquafosol 3% in Dry Eye.

PURPOSE: To evaluate the efficacy and safety of cyclosporine nanoemulsion 0.05% compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. METHODS: This was a multicenter, randomized, evaluator-masked, active control, parallel, phase IV study. A total of 227 patients were randomly allocated to instill cyclosporine nanoemulsion 0.05% (CN) twice daily, cyclosporine emulsion 0.05% (CE) twice daily, or diquafosol sodium 3% (DQ) six times daily. Non-inferiority of CN was analyzed by primary endpoint (cornea and conjunctival staining scores at week 12). The secondary endpoints were scores of corneal staining, conjunctival staining, tear break-up time, Schirmer test, and Ocular Surface Disease Index at weeks 4 and 12. RESULTS: Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were -6.60 for the CN group, -5.28 for the CE group, and -6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, -0.15 to 2.80, Δ>-2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4. CONCLUSIONS: Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.

Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

BACKGROUND: This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). METHODS: This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. RESULTS: At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by - 6.60 for CN and - 6.63 for DQ group (all P < 0.0001, P = 0.9739 between groups). TBUT and Schirmer values for CN were significantly improved from the baseline at 4 and 12 weeks (P = 0.0034, P < 0.0001 for TBUT, P = 0.0418, P = 0.0031 for Schirmer test). However, for DQ, TBUT showed significant improvement at 12 weeks only (P = 0.0281). Mean OSDI score differences from the baseline to 12 weeks were improved by - 13.03 ± 19.63 for CN and - 16.11 ± 20.87 for DQ, respectively (all P < 0.0001, P = 0.854 between groups). Regarding drug compliance, the mean instillation frequency of CN was less than that of DQ (P < 0.001). There were no statistically significant intergroup differences in safety evaluation. CONCLUSIONS: The level of improvement regarding NEI, TBUT, and OSDI scores were not significantly different between the two treatment groups. However, with regards to the early improvement of TBUT and patient compliance, patients using CN improved faster and with greater adherence to drug usage than did those treated with DQ. TRIAL REGISTRATION: KCT0002180 , retrospectively registered on 23 December 2016.