Development of Cell Culture Platforms for Study of Trabecular Meshwork Cells and Glaucoma Development.

BACKGROUND: Various cell culture platforms that could display native environmental cue-mimicking stimuli were developed, and effects of environmental cues on cell behaviors were studied with the cell culture platforms. Likewise, various cell culture platforms mimicking native trabecular meshwork (TM) composed of juxtacanalicular, corneoscleral and uveal meshwork located in internal scleral sulcus were used to study effects of environmental cues and/or drug treatments on TM cells and glaucoma development. Glaucoma is a disease that could cause blindness, and cause of glaucoma is not clearly identified yet. It appears that aqueous humor (AH) outflow resistance increased by damages on pathway of AH outflow can elevate intraocular pressure (IOP). These overall possibly contribute to development of glaucoma. METHODS: For the study of glaucoma, static and dynamic cell culture platforms were developed. Particularly, the dynamic platforms exploiting AH outflow-mimicking perfusion or increased IOP-mimicking increased pressure were used to study how perfusion or increased pressure could affect TM cells. Overall, potential mechanisms of glaucoma development, TM structures and compositions, TM cell culture platform types and researches on TM cells and glaucoma development with the platforms were described in this review. RESULTS AND CONCLUSION: This will be useful to improve researches on TM cells and develop enhanced therapies targeting glaucoma.

Analysis of the influence of host lifestyle (coffee consumption, drinking, and smoking) on Korean oral microbiome.

If a DNA sample collected in the field is old or degraded, short tandem repeat analysis is difficult to perform, a representative analysis method currently used for individual identification. Given that microorganisms exist everywhere and within the human body, in similar amounts to human cells, microbial analysis could be used to identify individuals even in cases in which human DNA-based identification is difficult. Research has demonstrated that the types of microorganisms within the human body differ depending on various internal or external factors, such as body part or bodily fluid type, lifestyle, geographical area of residence, sex, and age. In this study, we aimed to examine the relationship between lifestyle factors and the composition and diversity of the oral microbiome in individuals living in Korea. We collected 43 saliva samples from Korean individuals and analyzed the oral microbiome and its variations due to external factors, such as coffee consumption, drinking, and smoking. Linear discriminant analysis effect size revealed that Oribacterium, Campylobacter, and Megasphaera were abundant in coffee consumers, whereas Saccharimonadales, Clostridia, and Catonella were abundant in alcohol non-drinkers. We found increased levels of Stomatobaculum in the saliva of smokers, compared with that of non-smokers. Thus, our analysis revealed characteristic microorganisms for each parameter that was evaluated (coffee consumption, smoking, drinking). Consequently, our study provides insight into the oral microbiome in the Korean population and lays the foundation for developing the Korean Forensic Microbiome Database.

Fibrous hydrogels by electrospinning: Novel platforms for biomedical applications.

Hydrogels, hydrophilic and biocompatible polymeric networks, have been used for numerous biomedical applications because they have exhibited abilities to mimic features of extracellular matrix (ECM). In particular, the hydrogels engineered with electrospinning techniques have shown great performances in biomedical applications. Electrospinning techniques are to generate polymeric micro/nanofibers that can mimic geometries of natural ECM by drawing micro/nanofibers from polymer precursors with electrical forces, followed by structural stabilization of them. By exploiting the electrospinning techniques, the fibrous hydrogels have been fabricated and utilized as 2D/3D cell culture platforms, implantable scaffolds, and wound dressings. In addition, some hydrogels that respond to external stimuli have been used to develop biosensors. For comprehensive understanding, this review covers electrospinning processes, hydrogel precursors used for electrospinning, characteristics of fibrous hydrogels and specific biomedical applications of electrospun fibrous hydrogels and highlight their potential to promote use in biomedical applications.

Primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor.

This report describes a woman with a rare primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor. A woman in her late 40s was referred for abdominal discomfort, which worsened during defecation. Pelvic magnetic resonance imaging showed a multiloculated cystic lesion in the left adnexa measuring approximately 7.5 × 9.5 × 7.0 cm. An intraoperatively obtained frozen biopsy sample of the mass in the left ovary was positive for malignancy, resulting in a surgical staging operation. The tumor was composed of squamous cell carcinoma and mucinous borderline tumor. There was no evidence of capsular invasion or invasion of other internal organs, including pelvic and para-aortic lymph nodes (0/41). Immunohistochemistry showed that the tumor was diffusely positive for cytokeratin 7, cytokeratin 20, Ki-67, and P40 but negative for P16. After a debulking operation, the patient has been monitored regularly without adjuvant therapy owing to final surgical staging of the tumor as stage IA.

Forensic authentication method for audio recordings generated by Voice Recorder application on Samsung Galaxy Watch4 series.

The number of smartwatch users has been rapidly increasing in recent years. A smartwatch is a wearable device that collects various types of data using sensors and provides basic functions, such as healthcare-related measurements and audio recording. In this study, we proposed the forensic authentication method for audio recordings from the Voice Recording application in the Samsung Galaxy Watch4 series. First, a total of 240 audio recordings from each of the four different models, paired with four different smartphones for synchronization via Bluetooth, were collected and verified. To analyze the characteristics of smartwatch audio recordings, we examined the transition of the audio latency, writable audio bandwidth, timestamps, and file structure between those generated in the smartwatches and those edited using the Voice Recording application of the paired smartphones. In addition, the devices with the audio recordings were examined via the Android Debug Bridge (ADB) tool and compared with the timestamps stored in the file system. The experimental results showed that the audio latency, writable audio bandwidth, and file structure of audio recordings generated by smartwatches differed from those generated by smartphones. Additionally, by analyzing the file structure, audio recordings can be classified as unmanipulated, manipulation has been attempted, or manipulated. Finally, we can forensically authenticate the audio recordings generated by the Voice Recorder application in the Samsung Galaxy Watch4 series by accessing the smartwatches and analyzing the timestamps related to the audio recordings in the file system.

Optimization of DNA extraction and sampling methods for successful forensic microbiome analyses of the skin and saliva.

Microbiome studies have contributed to many fields, such as healthcare and medicine; however, these studies are relatively limited in forensics. Microbiome analyses can provide information, such as geolocation and ancestry information, when short tandem repeat (STR) profiling fails. In this study, methods for DNA extraction and sampling from the skin and saliva were optimized for the construction of a Korean Forensic Microbiome Database (KFMD). DNA yields were estimated using four DNA extraction kits, including two automated kits (Maxwell® FSC DNA IQ™ Casework Kit and PrepFiler™ Forensic DNA Extraction Kit, updated) and two manual kits (QIAamp DNA Mini Kit and QIAamp DNA Micro Kit) commonly used in forensic DNA profiling laboratories. Next-generation sequencing of the 16S rRNA V4 region was performed to analyze microbial communities in samples. The Bacterial Transport Swab with Liquid Media (NobleBio), two cotton swabs (PoongSung and Puritan), and nylon-flocked swabs (NobleBio and COPAN) were tested for DNA recovery. The PrepFiler and Maxwell kits showed the highest yields of 3.884 ng/µL and 23.767 ng/µL from the scalp and saliva, respectively. With respect to DNA recovery, nylon-flocked swabs performed better than cotton swabs. The relative abundances of taxa sorted by DNA extraction kits were similar contributions; however, with significant differences in community composition between scalp and saliva samples. Lawsonella and Veillonella were the most abundant genera in the two sample types. Thus, the Maxwell® FSC DNA IQ™ Casework Kit and nylon-flocked swab (NobleBio) were optimal for DNA extraction and collection in microbiome analyses.

Advanced forensic procedure for the authentication of audio recordings generated by Voice Memos application of iOS14.

In this study, we propose an advanced forensic examination procedure for audio recordings generated by the Voice Memos application with iPhone Operation System (iOS)14, to verify that these are the original recordings and have not been manipulated. The proposed examination procedure consists of an analysis of the characteristics of audio recordings and of the file system of the device storing the audio recordings. To analyze the characteristics of audio recordings, we compare the encoding parameters (bitrate, sampling rate, timestamps, etc.) and the file structure to determine whether audio recordings were manipulated. Next, in the device examination step, we analyze the media-log history and temporary files of the file system obtained by mobile forensic tools. For comparative analysis, a total of 100 audio recording samples were obtained through the Voice Memos application from five iPhone mobile handsets of different models with iOS14 installed using Advanced audio coding (AAC) or Apple lossless audio codec (ALAC). As a result of analyzing the encoding parameters between the original and manipulated audio recordings, as well as the temporary files contained in the device file system, the difference in the encoding parameters and the very unique trace of the original audio recordings in the temporary files were confirmed when manipulating the audio recordings. In particular, the primary advantage of our proposed method is its potential ability to recover original audio recordings that were subsequently manipulated via the temporary files examined in the device file system analysis.

Levels of endoplasmic reticulum stress-related mRNA in peritoneal fluid of patients with endometriosis or gynaecological cancer.

OBJECTIVE: To compare the levels of endoplasmic reticulum (ER) stress-associated mRNAs and the clinical characteristics of patients with endometriosis or gynaecological cancer. METHODS: This prospective study obtained intraperitoneal fluid samples from female patients that underwent surgery. The levels of ER stress mRNAs in the peritoneal fluid, including C/EBP-homologous protein (CHOP), X-box binding protein 1 (sXBP1), activating transcription factor 6 (ATF6), immunoglobulin heavy chain-binding protein (BiP), inositol-requiring enzyme 1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), were measured using real-time reverse transcription-polymerase chain reaction in patients with benign disease without endometriosis (control group), with endometriosis or with gynaecological cancer. RESULTS: This study enrolled 126 patients: 46 control patients; 47 with endometriosis; and 33 with cancer. The levels of CHOP and BiP mRNA were significantly higher in the control group compared with the cancer group. Levels of sXBP1 and ATF6 mRNA were significantly higher in the cancer group than in the control and endometriosis groups. In the endometriosis group, ATF6 mRNA level was inversely correlated with age and positively correlated with serum cancer antigen 125 levels; and ATF6 and PERK mRNA levels were inversely correlated with parity. CONCLUSION: The levels of ER stress-related mRNAs were related to the pathogenesis of endometriosis and gynaecological cancers.

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic.

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.

A method of forensic authentication of audio recordings generated using the Voice Memos application in the iPhone.

Considering the widespread use of mobile phones, audio recordings of crime scenes are widely used as digital evidence; however, it is important to authenticate the audio recordings before consideration as legal evidence. This study aimed to develop a method to authenticate audio recordings generated using the iPhone through three steps: 1) bitrate/audio latency time analysis of audio recordings, 2) comparison of the file structure/timestamp on audio recordings, and 3) device-based log history examinations for the provenance of audio recordings. Herein, we analyzed audio recording samples from ten different models of mobile handsets of the iPhone with Advanced Audio Coding (AAC) or Apple Lossless Audio Codec (ALAC), through the Voice Memos application depending on the iPhone Operating System (iOS). To analyze the characteristics of these audio recordings, we compared features including audio latency, file format/structure, and timestamps between the audio recordings generated in the iPhone and those edited through the built-in audio editing function. Furthermore, we investigated the log history registered in devices during the generation of the audio recordings. Differences in the audio latency, file size, timestamps, bitrate, and log history were confirmed on the iPhone when manipulating the audio recordings. The present results show that it is possible to verify the authentication of audio recordings generated using the Voice Memos application on iPhone.

Effects of prolonged continuous computer gaming on physical and ocular symptoms and binocular vision functions in young healthy individuals.

BACKGROUND AND OBJECTIVE: Addiction to computer gaming has become a social problem in Korea and elsewhere, and it has been enlisted as a mental health disorder by the World Health Organization. Most studies related to computer use and vision have individually assessed physical and ocular symptoms and binocular vision. Accordingly, the present study comprehensively assessed subjective physical and ocular symptoms and functions related to binocular vision after prolonged continuous computer gaming. This study aimed to investigate the effects of prolonged continuous computer gaming on physical and ocular health and visual functions in young healthy individuals. METHODS: Fifty healthy college students (35 male/15 female), aged 19-35 years old, were enrolled in this study. The inclusion criteria were no binocular vision problems and no reported history of ocular disease. Participants played continuously for 4 h from 6:00 to 10:00 p.m. Physical and ocular symptoms and visual functions such as convergence, accommodation, phoria, and the blink rate were assessed before and after continuous computer gaming for 4 h. RESULTS: Continuous computer gaming for 4 h resulted in convergence and accommodation disturbances and increased physical and ocular discomfort. Near phoria showed an exophoric shift, whereas distance phoria showed no change. Moreover, the accommodative and vergence facilities and blink rate were significantly decreased. All visual functions recovered to the baseline levels by the following morning. DISCUSSION: Our findings suggest that excessive and continuous computer gaming impairs visual functions and causes ocular and physical fatigue. Our findings further the understanding of the adverse effects of excessive computer use on physical and ocular health, and adequate breaks are necessary to reduce physical and visual discomfort during computer gaming.

A Survey on Banknote Recognition Methods by Various Sensors.

Despite a decrease in the use of currency due to the recent growth in the use of electronic financial transactions, real money transactions remain very important in the global market. While performing transactions with real money, touching and counting notes by hand, is still a common practice in daily life, various types of automated machines, such as ATMs and banknote counters, are essential for large-scale and safe transactions. This paper presents studies that have been conducted in four major areas of research (banknote recognition, counterfeit banknote detection, serial number recognition, and fitness classification) in the accurate banknote recognition field by various sensors in such automated machines, and describes the advantages and drawbacks of the methods presented in those studies. While to a limited extent some surveys have been presented in previous studies in the areas of banknote recognition or counterfeit banknote recognition, this paper is the first of its kind to review all four areas. Techniques used in each of the four areas recognize banknote information (denomination, serial number, authenticity, and physical condition) based on image or sensor data, and are actually applied to banknote processing machines across the world. This study also describes the technological challenges faced by such banknote recognition techniques and presents future directions of research to overcome them.

Determination and characterization of pharmaceuticals in sludge from municipal and livestock wastewater treatment plants.

This study investigated 24 pharmaceuticals compounds belonging to the classes of analgesics, stimulants, anti-seizures, non-steroidal anti-inflammatory drugs (NSAIDs), and antibiotics in the sludge of 12 municipal sewage treatment plants (S-sludge) and 4 livestock wastewater treatment plants (L-sludge) located across Korea. Over 70% of the target compounds were detected in at least one sample of S-sludge and L-sludge. The total concentration of the target pharmaceutical compounds detected in S-sludge was 2.622-422.8 mg kg-1and the most dominant compound was acetylsalicylic acid (ASA: 0.374-367.0 mg kg-1) whereas in L-sludge, the total concentration was 43.87-156.8 mg kg-1and the most abundant compound was oxytetracycline (OTC: 34.54-86.39 mg kg-1). Cluster analysis revealed two distinct groups: group A, which were S-sludge samples including ASA, carbamazepine (CBM), and others, and group B were L-sludge samples, dominated by antibiotics (CTC, OTC, LIN). The total daily load amount of the target pharmaceuticals in S-sludge was 0.010-268.9 kg day-1 while the L-sludge was 0.021-0.529 kg day-1. The estimated amounts of the target pharmaceutical discharged from S-sludge and L-sludge into the Korean environment were 150.2 ± 47.94 ton yr-1 and 15.05 ± 5.671 ton yr-1 respectively, but the discharged amount of antibiotics from S-sludge (6.945 ton yr-1) was lower than that from L-sludge (9.234 ton yr-1).

Enantioselective N-demethylation and hydroxylation of sibutramine in human liver microsomes and recombinant cytochrome p-450 isoforms.

The enantioselective metabolism of sibutramine was examined using human liver microsomes (HLM) and recombinant cytochrome P-450 (CYP) isoforms. This drug is metabolized to N-mono-desmethyl- (M1) and N,N-di-desmethylsibutramine (M2), and subsequent hydroxylation results in hydroxyl M1 (HM1) and hydroxyl M2 (HM2). No significant difference was noted in formation of M1from sibutramine between R- and S-sibutramine in HLM. However, S-enantiomers of M1 and M2 were preferentially metabolized to M2, HM1, and HM2compared to R-enantiomers in HLM, and intrinsic clearance (Clint) ratios of S-enantiomers/R-enantiomers were 1.97, 4.83, and 9.94 for M2, HM1, and HM2, respectively. CYP3A4 and CYP3A5 were only involved in the formation of M1, whereas CYP2B6 and CYP2C19 were responsible for all metabolic reactions of sibutramine. CYP2C19 and CYP3A5 displayed catalytic preference for S-sibutramine to S-M1, whereas CYP2B6 and CYP3A4 showed little or no stereoselectivity in metabolism of sibutramine to M1. In the case of M2 formation, CYP2B6 metabolized S-M1 more rapidly than R-M1 with a Clint ratio of 2.14. However, CYP2C19 catalyzed less S-M1 than R-M1 and the Clint ratio of S-M1 to R-M1 was 0.65. The most significant enantioselectivity was observed in formation of HM1 from M1, and HM2 from M2. CYP2B6 and CYP2C19 exhibited preferential catalysis of formation of hydroxyl metabolites from S-enantiomers rather than R-enantiomers. These results indicate that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibutramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramine and co-administered drugs.

Nonwearable gaze tracking system for controlling home appliance.

A novel gaze tracking system for controlling home appliances in 3D space is proposed in this study. Our research is novel in the following four ways. First, we propose a nonwearable gaze tracking system containing frontal viewing and eye tracking cameras. Second, our system includes three modes: navigation (for moving the wheelchair depending on the direction of gaze movement), selection (for selecting a specific appliance by gaze estimation), and manipulation (for controlling the selected appliance by gazing at the control panel). The modes can be changed by closing eyes during a specific time period or gazing. Third, in the navigation mode, the signal for moving the wheelchair can be triggered according to the direction of gaze movement. Fourth, after a specific home appliance is selected by gazing at it for more than predetermined time period, a control panel with 3 × 2 menu is displayed on laptop computer below the gaze tracking system for manipulation. The user gazes at one of the menu options for a specific time period, which can be manually adjusted according to the user, and the signal for controlling the home appliance can be triggered. The proposed method is shown to have high detection accuracy through a series of experiments.

Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty.

PURPOSE: Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. METHODS: This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. RESULTS: Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. CONCLUSION: Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea.

We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60-3.03 and 0.17-1.68ngkg(-1)bwd(-1) for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150ngkg(-1)bwd(-1); PFOA: 1500ngkg(-1)bwd(-1)). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water).

The ratio of estimated average glucose to fasting plasma glucose level is superior to glycated albumin, hemoglobin A1c, fructosamine, and GA/A1c ratio for assessing ß-cell function in childhood diabetes.

OBJECTIVE: This study investigated the use of the estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to screen for ß-cell function in pediatric diabetes. METHODS: Glycated hemoglobin (HbA1c), glycated albumin (GA), fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c (GA/A1c ratio) was calculated, and the homeostasis model assessment of ß-cell function (HOMA-ß) was determined. RESULTS: Median values of C-peptide, insulin, and HOMA-ß levels were significantly higher in patients with an increased eAG/fPG ratio than in those with a decreased eAG/fPG ratio. C-peptide and HOMA-ß levels were more closely correlated with the eAG/fPG ratio than with GA, HbA1c, the GA/A1c ratio, and fructosamine. In contrast, body mass index was significantly associated with GA, GA/A1c ratio, and fructosamine, but not with the eAG/fPG ratio and HbA1c levels. To test the diagnostic accuracies of the eAG/fPG ratio for identifying HOMA-ß>30.0% in patients with type 2 diabetes, the area under the ROC curve of the eAG/fPG ratio was significantly larger than that of the GA/A1c ratio [0.877 (95% CI, 0.780-0.942) versus 0.775 (95% CI, 0.664-0.865), P=0.039]. CONCLUSIONS: A measurement of the eAG/fPG ratio may provide helpful information for assessing ß-cell function in pediatric patients with diabetes.

A novel gaze tracking method based on the generation of virtual calibration points.

Most conventional gaze-tracking systems require that users look at many points during the initial calibration stage, which is inconvenient for them. To avoid this requirement, we propose a new gaze-tracking method with four important characteristics. First, our gaze-tracking system uses a large screen located at a distance from the user, who wears a lightweight device. Second, our system requires that users look at only four calibration points during the initial calibration stage, during which four pupil centers are noted. Third, five additional points (virtual pupil centers) are generated with a multilayer perceptron using the four actual points (detected pupil centers) as inputs. Fourth, when a user gazes at a large screen, the shape defined by the positions of the four pupil centers is a distorted quadrangle because of the nonlinear movement of the human eyeball. The gaze-detection accuracy is reduced if we map the pupil movement area onto the screen area using a single transform function. We overcame this problem by calculating the gaze position based on multi-geometric transforms using the five virtual points and the four actual points. Experiment results show that the accuracy of the proposed method is better than that of other methods.

Caffeic acid phenethyl ester activation of Nrf2 pathway is enhanced under oxidative state: structural analysis and potential as a pathologically targeted therapeutic agent in treatment of colonic inflammation.

Caffeic acid phenethyl ester (CAPE) is a polyphenolic natural product that possesses numerous biological activities including anti-inflammatory effects. CAPE-mediated nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2) activation is likely responsible for some of its biological effects. CAPE was chemically modified to yield CAPE analogues that were subjected to experiments examining cellular Nrf2 activity. CAPE and the CAPE analogue with a catechol moiety, but not the other analogues, activated the Nrf2 pathway. In addition, only biotin-labeled CAPE analogues with the catechol moiety precipitated Kelch-like ECH associated protein 1 (Keap1) when incubated with cell lysates and streptavidin agarose beads. Sodium hypochlorite (NaOCl) oxidation of the catechol moiety in CAPE produced an oxidized, electrophilic form of CAPE (Oxi-CAPE) and greatly enhanced the ability of CAPE to activate Nrf2 and to bind to Keap1. Rectal administration of CAPE ameliorated 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis and activated the Nrf2 pathway in the inflamed colon, and incubation of CAPE in the lumen of the inflamed distal colon generated Oxi-CAPE. However, these biological effects and chemical change of CAPE were not observed in the normal colon. Our data suggest that CAPE requires the catechol moiety for the oxidation-enhanced activation of the Nrf2 pathway and has potential as a pathologically targeted Nrf2-activating agent that is exclusively activated in pathological states with oxidative stress such as colonic inflammation.