Unveiling the Nanoconfinement Effect on Crystallization of Semicrystalline Polymers Using Coarse-Grained Molecular Dynamics Simulations.

Semicrystalline polymers under nanoconfinement show distinct structural and thermomechanical properties compared to their bulk counterparts. Despite extensive research on semicrystalline polymers under nanoconfinement, the nanoconfinement effect on the local crystallization process and the unique structural evolution of such polymers have not been fully understood. In this study, we unveil such effects by using coarse-grained molecular dynamics simulations to study the crystallization process of a model semicrystalline polymer-polyvinyl alcohol (PVA)-under different levels of nanoconfinement induced by nanoparticles that are represented implicitly. We quantify in detail the evolution of the degree of crystallinity (XC) of PVA and examine distinct crystalline regions from simulation results. The results show that nanoconfinement can promote the crystallization process, especially at the early stage, and the interfaces between nanoparticles and polymer can function as crystallite nucleation sites. In general, the final XC of PVA increases with the levels of nanoconfinement. Further, nanoconfined cases show region-dependent XC with higher and earlier increase of XC in regions closer to the interfaces. By tracking region-dependent XC evolution, our results indicate that nanoconfinement can lead to a heterogenous crystallization process with a second-stage crystallite nucleation in regions further away from the interfaces. In addition, our results show that even under very high cooling rates, the nanoconfinement still promotes the crystallization of PVA. This study provides important insights into the underlying mechanisms for the intricate interplay between nanoconfinement and the crystallization behaviors of semicrystalline polymer, with the potential to guide the design and characterization of semicrystalline polymer-based nanocomposites.

Classification of a 3D Film Pattern Image Using the Optimal Height of the Histogram for Quality Inspection.

A 3D film pattern image was recently developed for marketing purposes, and an inspection method is needed to evaluate the quality of the pattern for mass production. However, due to its recent development, there are limited methods to inspect the 3D film pattern. The good pattern in the 3D film has a clear outline and high contrast, while the bad pattern has a blurry outline and low contrast. Due to these characteristics, it is challenging to examine the quality of the 3D film pattern. In this paper, we propose a simple algorithm that classifies the 3D film pattern as either good or bad by using the height of the histograms. Despite its simplicity, the proposed method can accurately and quickly inspect the 3D film pattern. In the experimental results, the proposed method achieved 99.09% classification accuracy with a computation time of 6.64 s, demonstrating better performance than existing algorithms.

Structure-Activity Relationships of Truncated 1'-Homologated Carbaadenosine Derivatives as New PPARγ/δ Ligands: A Study on Sugar Puckering Affecting Binding to PPARs.

Peroxisome proliferator-activated receptors (PPARs) are associated with the regulation of metabolic homeostasis. Based on a previous report that 1'-homologated 4'-thionucleoside acts as a dual PPARγ/δ modulator, carbocyclic nucleosides 2-5 with various sugar conformations were synthesized to determine whether sugar puckering affects binding to PPARs. (S)-conformer 2 was synthesized using Charette asymmetric cyclopropanation, whereas (N)-conformer 3 was synthesized using stereoselective Simmons-Smith cyclopropanation. All synthesized nucleosides did not exhibit binding affinity to PPARα but exhibited significant binding affinities to PPARγ/δ. The binding affinity of final nucleosides to PPARγ did not differ significantly based on their conformation, but their affinity to PPARδ depended greatly on their conformation, correlated with adiponectin production. (N)-conformer 3h was discovered to be the most potent PPARδ antagonist with good adiponectin production, which exhibited the most effective activity in inhibiting the mRNA levels of LPS-induced IL-1ß expression in RAW 264.7 macrophages, implicating its anti-inflammatory activity.

Changes in the management of hypertension, diabetes mellitus, and hypercholesterolemia in Korean adults before and during the COVID-19 pandemic: data from the 2010-2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: This study aimed to analyze the changes in chronic disease management indicators, including hypertension, diabetes mellitus, and hypercholesteremia, from 2010-2020 and before (2019) and during (2020) the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study included 58,504 individuals aged ≥30 years who participated in the Korea National Health and Nutrition Examination Survey 2010-2020. Trends in the prevalence, awareness, treatment, and control of chronic diseases and the difference in those between before and during the COVID-19 pandemic were analyzed using the SAS program PROC SURVEYREG. RESULTS: From 2010-2020, the awareness, treatment, and control in adults aged ≥30 years for hypertension and hypercholesterolemia continuously improved, whereas no significant change in the management indicators of diabetes mellitus was observed. The prevalence of hypertension, diabetes mellitus, and hypercholesterolemia in men increased from before to during the COVID- 19 pandemic. However, there was no significant change in the management indicators of hypertension and diabetes mellitus in men and women, and the awareness, treatment, and control rates for hypercholesterolemia increased by 5.5%p, 6.9%p, and 4.1%p respectively. CONCLUSIONS: In 2020, the first year of the COVID-19 pandemic, the prevalence of hypertension, diabetes mellitus, and hypercholesterolemia increased, but the management indicators of the chronic diseases did not significantly deteriorate. Considering the ongoing COVID-19 pandemic, it is necessary to monitor changes in chronic disease management indicators and to develop efficient and accessible chronic disease prevention and management programs.

Changes in food and nutrient intakes in Korean adults before and during the COVID-19 pandemic: data from the 2011-2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: This study was to examine the changes in dietary habits and food and nutrient intakes between before (2019) and during (2020) the coronavirus disease 2019 (COVID-19) pandemic from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 54,995 participants aged ≥19 years who participated in the 2011-2020 KNHANES were included. The 10-year trend (2011-2020) and differences between 2019 and 2020 for dietary habits and food and nutrient intakes were estimated using SAS. RESULTS: In the past 10 years (2011-2020), the dietary habits (increase in skipping meals and eating out), food intake (increase in meats and decrease in fruits and vegetables), and nutrient intake (increase in fat and decrease in sodium) in adults have changed. When comparing between 2019 and 2020, there were 4.6%p decrease in the eating out more than once a day. On the other hand, there were no significant differences in the intakes of food, energy and most of nutrients between 2019 and 2020, except for the proportion of energy intake from fat (1.0%p increase) and carbohydrate (1.0%p decrease). CONCLUSIONS: Although a change in dietary habits from before to during the COVID-19 pandemic was observed, food and nutrient intakes have not deteriorated markedly and appear similar to the trends in the past 10 years. Throughout the COVID-19 pandemic, it is necessary to monitor the effects of changes in dietary habits on health as well as food and nutrient intakes.

Design, Synthesis, and Biological Activity of l-1'-Homologated Adenosine Derivatives.

On the basis of the previously reported polypharmacological profile of truncated d-1'-homologated adenosine derivatives [J. Med. Chem.2020, 63, 16012], the l-nucleoside analogues were synthesized using computer-aided design and evaluated for biological activity. The target molecules were synthesized from d-ribose via the key intramolecular cyclization of the monotosylate and Mitsunobu condensation. The peroxisome proliferator-activated receptor (PPAR) binding activities of l-nucleoside analogue 2d (K i = 4.3 µM for PPARγ and 1.0 µM for PPARδ) were significantly improved in comparison with those of the d-nucleoside compound 1 (11.9 and 2.7 µM, respectively). In addition, the l-nucleosides showed more potent adiponectin-secretion-promoting activity than the d-nucleoside analogues.

Physiological Functions of Thiol Peroxidases (Gpx1 and Prdx2) during Xenopus laevis Embryonic Development.

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using Xenopus laevis as a vertebrate model. Our investigations revealed the zygotic nature of gpx1 having its localization in the eye region of developing embryos, whereas prdx2 exhibited a maternal nature and were localized in embryonic ventral blood islands. Furthermore, the gpx1-morphants exhibited malformed eyes with incompletely detached lenses. However, the depletion of prdx2 has not established its involvement with embryogenesis. A molecular analysis of gpx1-depleted embryos revealed the perturbed expression of a cryba1-lens-specific marker and also exhibited reactive oxygen species (ROS) accumulation in the eye regions of gpx1-morphants. Additionally, transcriptomics analysis of gpx1-knockout embryos demonstrated the involvement of Wnt, cadherin, and integrin signaling pathways in the development of malformed eyes. Conclusively, our findings indicate the association of gpx1 with a complex network of embryonic developmental pathways and ROS responses, but detailed investigation is a prerequisite in order to pinpoint the mechanistic details of these interactions.

IL-33-Induced Transcriptional Activation of LPIN1 Accelerates Breast Tumorigenesis.

Phospholipids are crucial materials that are not only required for cell membrane construction but also play significant roles as signaling molecules. LPIN1 is an enzyme that displays phosphatidate phosphatase activity in the triglyceride and phospholipid synthesis pathway. Recent studies have shown that overexpression of LPIN1 is involved in breast tumorigenesis, but the underlying mechanism regulating LPIN1 expression has not been elucidated yet. In the present study, we showed that the IL-33-induced COT-JNK1/2 signaling pathway regulates LPIN1 mRNA and protein expression by recruiting c-Jun to the LPIN1 promoter in breast cancer cells. IL-33 dose-dependently and time-dependently increased LPIN1 mRNA and protein expression. Moreover, IL-33 promoted colony formation and mammary tumorigenesis via induction of LPIN1 expression, while inhibition of LPIN1 disturbed IL-33-induced cell proliferation and mammary tumorigenesis. IL-33-driven LPIN1 expression was mediated by the COT-JNK1/2 signaling pathway, and inhibition of COT or JNK1/2 reduced LPIN1 expression. COT-JNK1/2-mediated IL-33 signaling activated c-Jun and promoted its binding to the promoter region of LPIN1 to induce LPIN1 expression. These findings demonstrated the regulatory mechanism of LPIN1 transcription by the IL-33-induced COT/JNK1/2 pathway for the first time, providing a potential mechanism underlying the upregulation of LPIN1 in cancer.

Design and Synthesis of 2,6-Disubstituted-4'-Selenoadenosine-5'-N,N-Dimethyluronamide Derivatives as Human A3 Adenosine Receptor Antagonists.

A new series of 4'-selenoadenosine-5'-N,N-dimethyluronamide derivatives as highly potent and selective human A3 adenosine receptor (hA3AR) antagonists, is described. The highly selective A3AR agonists, 4'-selenoadenosine-5'-N-methyluronamides were successfully converted into selective antagonists by adding a second N-methyl group to the 5'-uronamide position. All the synthesized compounds showed medium to high binding affinity at the hA3AR. Among the synthesized compounds, 2-H-N6-3-iodobenzylamine derivative 9f exhibited the highest binding affinity at hA3AR. (Ki = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N6-3-iodobenzylamine derivative 9l demonstrated hA3AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5'-uronamide as an essential hydrogen bonding donor for hA3AR activation.

Discovery and Structure-Activity Relationships of Novel Template, Truncated 1'-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators.

Following our report that A3 adenosine receptor (AR) antagonist 1 exhibited a polypharmacological profile as a dual modulator of peroxisome proliferator-activated receptor (PPAR)γ/δ, we discovered a new template, 1'-homologated adenosine analogues 4a-4t, as dual PPARγ/δ modulators without AR binding. Removal of binding affinity to A3AR was achieved by 1'-homologation, and PPARγ/δ dual modulation was derived from the structural similarity between the target nucleosides and PPAR modulator drug, rosiglitazone. All the final nucleosides were devoid of AR-binding affinity and exhibited high binding affinities to PPARγ/δ but lacked PPARα binding. 2-Cl derivatives exhibited dual receptor-binding affinity to PPARγ/δ, which was absent for the corresponding 2-H derivatives. 2-Propynyl substitution prevented PPARδ-binding affinity but preserved PPARγ affinity, indicating that the C2 position defines a pharmacophore for selective PPARγ ligand designs. PPARγ/δ dual modulators functioning as both PPARγ partial agonists and PPARδ antagonists promoted adiponectin production, suggesting their therapeutic potential against hypoadiponectinemia-associated cancer and metabolic diseases.

RhoA/ROCK Regulates Prion Pathogenesis by Controlling Connexin 43 Activity.

Scrapie infection, which converts cellular prion protein (PrPC) into the pathological and infectious isoform (PrPSc), leads to neuronal cell death, glial cell activation and PrPSc accumulation. Previous studies reported that PrPC regulates RhoA/Rho-associated kinase (ROCK) signaling and that connexin 43 (Cx43) expression is upregulated in in vitro and in vivo prion-infected models. However, whether there is a link between RhoA/ROCK and Cx43 in prion disease pathogenesis is uncertain. Here, we investigated the role of RhoA/ROCK signaling and Cx43 in prion diseases using in vitro and in vivo models. Scrapie infection induced RhoA activation, accompanied by increased phosphorylation of LIM kinase 1/2 (LIMK1/2) at Thr508/Thr505 and cofilin at Ser3 and reduced phosphorylation of RhoA at Ser188 in hippocampal neuronal cells and brains of mice. Scrapie infection-induced RhoA activation also resulted in PrPSc accumulation followed by a reduction in the interaction between RhoA and p190RhoGAP (a GTPase-activating protein). Interestingly, scrapie infection significantly enhanced the interaction between RhoA and Cx43. Moreover, RhoA and Cx43 colocalization was more visible in both the membrane and cytoplasm of scrapie-infected hippocampal neuronal cells than in controls. Finally, RhoA and ROCK inhibition reduced PrPSc accumulation and the RhoA/Cx43 interaction, leading to decreased Cx43 hemichannel activity in scrapie-infected hippocampal neuronal cells. These findings suggest that RhoA/ROCK regulates Cx43 activity, which may have an important role in the pathogenesis of prion disease.

Acoustic analysis of ultrasonic assisted soldering for enhanced adhesion.

Ultrasonic soldering utilizes high-intensity acoustic fields to induce cavitation in the solder melt in order to (i) bond dissimilar materials and (ii) improve solder joint strength. The acoustic energy transfer from the piezoelectric transducer (PZT) into the liquid solder pool is critical in both understanding and optimizing this process. We use finite element analysis of the acoustics and compare with experiment. Our finite-element modeling approach is two-pronged; (i) we develop a one-dimensional model that is used as a design tool to optimize the solder stack geometry to match the transducer frequency for maximal acoustic energy transfer and (ii) we use a three-dimensional model to compute the frequency response in the solder stack assembly (solid acoustics) and the acoustic pressure in the liquid solder pool (solid-fluid interaction). The acoustic pressure is a proxy for cavitation and therefore bond strength. Our simulations show the acoustic pressure rapidly decreases as the height of the solder tip above the substrate surface increases, which correlates with controlled experiments that show the solder bond quality also decreases with increasing tip height.

Selenium bioisosteric replacement of adenosine derivatives promoting adiponectin secretion increases the binding affinity to peroxisome proliferator-activated receptor δ.

N6-(3-Iodobenzyl)adenosine-5'-N-methyluronamide (1a, IB-MECA) exhibited polypharmacological characteristics targeting A3 adenosine receptor (AR), peroxisome proliferator-activated receptor (PPAR) γ, and PPARδ, simultaneously. The bioisosteric replacement of oxygen in 4'-oxoadenosines with selenium significantly increased the PPARδ-binding activity. 2-Chloro-N6-(3-iodobenzyl)-4'-selenoadenosine-5'-N-methyluronamide (3e) and related 4'-selenoadenosine derivatives significantly enhanced adiponectin biosynthesis during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). The PPARδ-binding affinity, but not the A3 AR binding affinity, of 4'-selenoadenosine derivatives correlated with their adiponectin secretion stimulation. Compared with the sugar ring of 4'-oxoadenosine, that of 4'-selenoadenosine was more favorable in forming the South sugar conformation. In the molecular docking simulation, the South sugar conformation of compound 3e formed additional hydrogen bonds inside the PPARδ ligand-binding pocket compared with the North conformation. Therefore, the sugar conformation of 4'-selenoadenosine PPAR modulators affects the ligand binding affinity against PPARδ.

Versatility of the pedicled buccal fat pad flap for the management of oroantral fistula: a retrospective study of 25 cases.

PURPOSE: Maxillary bone grafts and implantations have increased over recent years despite a lack of maxillary bone quality and quantity. The number of patients referred for oroantral fistula (OAF) due to implant or bone graft failure has increased, and in patients with an oroantral fistula, the pedicled buccal fat pad is viewed as a robust, reliable option. This study was conducted to document the usefulness of buccal fat pad grafts for oroantral fistula closure. MATERIALS AND METHODS: We retrospectively studied 25 patients with OAF treated with a buccal fat pad graft from 2015 to 2018. Sex, age, OAF location, cause, duration, presence of systemic disease, smoking, previous dental surgery, and side effects were investigated. RESULTS: A total of 25 patients were studied. Mean patient age was 54.8 years, and the male to female ratio was 19:6. Causes of oroantral fistula were cyst enucleation, tumor resection, implant removal, bone graft failure, and extraction. Excellent results were obtained in 23 (92%) of the 25 patients. In the other two patients that both smoked, a small fistula was observed during follow-up. No recurrence of oroantral fistula was observed after 2 months to 1 year of follow-up. CONCLUSIONS: The incidence of oroantral fistula is increasing due to implant and bone graft failures. Oroantral fistula closure using a pedicled buccal fat pad was found to have a high success rate.

Indirect Force Control of a Cable-Driven Parallel Robot: Tension Estimation using Artificial Neural Network trained by Force Sensor Measurements.

In a cable-driven parallel robot (CDPR), force sensors are utilized at each winch motor to measure the cable tension in order to obtain the force distribution at the robot end-effector. However, because of the effects of friction in the pulleys and the unmodeled cable properties of the robot, the measured cable tensions are often inaccurate, which causes force-control difficulties. To overcome this issue, this paper presents an artificial neural network (ANN)-based indirect end-effector force-estimation method, and its application to CDPR force control. The pulley friction and other unmodeled effects are considered as black-box uncertainties, and the tension at the end-effector is estimated by compensating for these uncertainties using an ANN that is developed using the training datasets from CDPR experiments. The estimated cable tensions at the end-effector are used to design a P-controller to track the desired force. The performance of the proposed ANN model is verified through comparisons with the forces measured directly at the end-effector. Furthermore, cable force control is implemented based on the compensated tensions to evaluate the performance of the CDPR in wrench space. The experimental results show that the proposed friction-compensation method is suitable for application in CDPRs to control the cable force.

Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice.

Scrapie is a mammalian transmissible spongiform encephalopathy or prion disease that predominantly affects sheep and goats. Scrapie has been shown to overcome the species barrier via experimental infection of other rodents. To confirm the re-transmissibility of the mouse-adapted ME7 scrapie strain to ovine prion protein (PrP) transgenic mice, mice of an ovinized transgenic mouse line carrying the Suffolk sheep PrP gene that contained the A136 R154 Q171/ARQ allele were intracerebrally inoculated with brain homogenates obtained from terminally ill ME7-infected C57BL/6J mice. Herein, we report that the mouse-adapted ME7 scrapie strain was successfully re-transmitted to the transgenic mice expressing ovine PrP. In addition, we observed changes in the incubation period, glycoform profile, and pattern of scrapie PrP (PrPSc) deposition in the affected brains. PrPSc deposition in the hippocampal region of the brain of 2nd-passaged ovine PrP transgenic mice was accompanied by plaque formation. These results reveal that the mouse-adapted ME7 scrapie strain has the capacity to act as a template for the conversion of ovine normal monomeric precursors into a pathogenic form in ovine PrP transgenic mice. The change in glycoform pattern and the deposition of plaques in the hippocampal region of the brain of the 2nd-passaged PrP transgenic mice are most likely cellular PrP species dependent rather than being ME7 scrapie strain encoded.

Strengthening of Aluminum Wires Treated with A206/Alumina Nanocomposites.

This study sought to characterize aluminum nanocomposite wires that were fabricated through a cold-rolling process, having potential applications in TIG (tungsten inert gas) welding of aluminum. A206 (Al-4.5Cu-0.25Mg) master nanocomposites with 5 wt % γAl2O3 nanoparticles were first manufactured through a hybrid process combining semi-solid mixing and ultrasonic processing. A206/1 wt % γAl2O3 nanocomposites were fabricated by diluting the prepared master nanocomposites with a monolithic A206 alloy, which was then added to a pure aluminum melt. The fabricated Al-γAl2O3 nanocomposite billet was cold-rolled to produce an Al nanocomposite wire with a 1 mm diameter and a transverse area reduction of 96%. Containing different levels of nanocomposites, the fabricated samples were mechanically and electrically characterized. The results demonstrate a significantly higher strength of the aluminum wires with the nanocomposite addition. Further, the addition of alumina nanoparticles affected the wires' electrical conductivity compared with that of pure aluminum and aluminum-copper alloys. The overall properties of the new material demonstrate that these wires could be an appealing alternative for fillers intended for aluminum welding.

Ultra-efficient Amplification of Abnormal Prion Protein by Modified Protein Misfolding Cyclic Amplification with Electric Current.

Prion diseases are clinically diagnosed and confirmed upon post-mortem histopathological examination of brain tissue. The only reliable molecular marker for prion diseases is abnormal prion protein (PrPSc), a pathologically conformed prion protein that primarily accumulates in the central nervous system and to a lesser extent in lymphoreticular tissues. However, the use of PrPSc as a marker for preclinical diagnoses is limited because the concentration of PrPSc in easily accessible body fluids is extremely low. Hence, one of the most promising approaches would be the development of an efficient in vitro amplification method for PrPSc. Indeed, protein misfolding cyclic amplification (PMCA) has become an important diagnostic tool for prion diseases. Here, we first describe a new superior PMCA device that employs electricity (referred to as ePMCA) to amplify PrPSc. The ePMCA device markedly improved the detection limit for PrPSc by amplifying trace amounts of pathogenic prion protein by applying electricity to improve PMCA. To increase the cavitation of sonication, a glass sample tube was used, and the upper side of the horn was shaped such that it had a curved cross-section. The ePMCA device enabled PrPSc to be amplified even from a sample seeded with 10-28-fold diluted 263K scrapie-infected brain homogenates with recombinant hamster prion protein (rHaPrP). In addition, the efficiency of prion amplification was best when 50 mM HEPES and 1% Triton X-100 were used as a PMCA conversion buffer in the various conditions that we applied. These results indicate that ePMCA would be very valuable for the rapid and specific diagnosis of human prion diseases and, thus, may provide a practically improved method for antemortem diagnoses using the body fluids of patients and animals with prion disease.

The rate and stability of mandibular block bone graft in recent 5 years.

BACKGROUND: The purposes of the present study were to compare implant stabilities of mandibular block bone graft and bovine bone graft and to evaluate influencing factors for implant stability in mandibular block bone (MBB) graft. METHODS: This retrospective study investigated 1224 cases and 389 patients treated by one surgeon in the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital (Yangsan, Korea) between January 2010 and December 2014. Proportions that MBB graft cases constitute in all implant restoration cases and in all bone graft cases were measured. Implant stability quotient (ISQ) values were achieved by the same surgeon before loading. The average ISQ values of the experimental groups were compared. In addition, ISQ values of influencing factors, such as age, sex, implant size, and implant placement site, were compared within the MBB group using OsstellTM Mentor (Osstell®, Göteborg, Sweden). Paired t test and ANOVA were conducted for statistical analysis with a significance level of 0.05. RESULTS: Fifty-five percent of all implant restoration cases performed bone graft while MBB cases constituted 34% of all implant restoration cases and 61% of all bone graft cases. Comparing ISQ values according to bone graft materials, the MBB group manifested sufficient implant stability by presenting comparable ISQ value to that of the experimental group without bone graft. Among the reviewed factors, females, mandibular molar regions, and implants in larger diameter displayed greater implant stabilities. CONCLUSIONS: Satisfactory implant stability was accomplished upon administration of MBB graft. Within the limitation of this study, gender, implant site, and implant diameter were speculated to influence on implant stability in MBB graft.

Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.

As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents.