RT-CLAD: Artificial Intelligence-Based Real-Time Chironomid Larva Detection in Drinking Water Treatment Plants.

The presence of chironomid larvae in tap water has sparked public concern regarding the water supply system in South Korea. Despite ongoing efforts to establish a safe water supply system, entirely preventing larval occurrences remains a significant challenge. Therefore, we developed a real-time chironomid larva detection system (RT-CLAD) based on deep learning technology, which was implemented in drinking water treatment plants. The acquisition of larval images was facilitated by a multi-spectral camera with a wide spectral range, enabling the capture of unique wavelet bands associated with larvae. Three state-of-the-art deep learning algorithms, namely the convolutional neural network (CNN), you only look once (YOLO), and residual neural network (ResNet), renowned for their exceptional performance in object detection tasks, were employed. Following a comparative analysis of these algorithms, the most accurate and rapid model was selected for RT-CLAD. To achieve the efficient and accurate detection of larvae, the original images were transformed into a specific wavelet format, followed by preprocessing to minimize data size. Consequently, the CNN, YOLO, and ResNet algorithms successfully detected larvae with 100% accuracy. In comparison to YOLO and ResNet, the CNN algorithm demonstrated greater efficiency because of its faster processing and simpler architecture. We anticipate that our RT-CLAD will address larva detection challenges in water treatment plants, thereby enhancing water supply security.

Chondroprotective Effects of 4,5-Dicaffeoylquinic Acid in Osteoarthritis through NF-κB Signaling Inhibition.

Osteoarthritis (OA) is characterized by cartilage degradation, inflammation, and pain. The dicaffeoylquinic acid (diCQA) isomer, 4,5-diCQA, exhibits antioxidant activity and various other health-promoting benefits, but its chondroprotective effects have yet to be elucidated. In this study, we aimed to investigate the chondroprotective effects of 4,5-diCQA on OA both in vitro and in vivo. Primary rat chondrocytes were pre-treated with 4,5-diCQA for 1 h before stimulation with interleukin (IL)-1ß (5 ng/mL). The accumulation of nitrite, PGE2, and aggrecan was observed using the Griess reagent and ELISA. The protein levels of iNOS, COX-2, MMP-3, MMP-13, ADMATS-4, MAPKs, and the NF-κB p65 subunit were measured by Western blotting. In vivo, the effects of 4,5-diCQA were evaluated for 2 weeks in a destabilization of the medial meniscus (DMM)-surgery-induced OA rat model. 4,5-diCQA significantly inhibited IL-1ß-induced expression of nitrite, iNOS, PGE2, COX-2, MMP-3, MMP-13, and ADAMTS-4. 4,5-diCQA also decreased the IL-1ß-induced degradation of aggrecan. It also suppressed the IL-1ß-induced phosphorylation of MAPKs and translocation of the NF-κB p65 subunit to the nucleus. These findings indicate that 4,5-diCQA inhibits DMM-surgery-induced cartilage destruction and proteoglycan loss in vivo. 4,5-diCQA may be a potential therapeutic agent for the alleviation of OA progression. In this study, diclofenac was set to be administered once every two days, but it showed an effect on OA. These results may be used as basic data to suggest a new dosing method for diclofenac.

Anti-Inflammatory Effect of 4,5-Dicaffeoylquinic Acid on RAW264.7 Cells and a Rat Model of Inflammation.

Anti-inflammatory agents that are safer and more effective than the currently used non-steroidal anti-inflammatory drugs are urgently needed. The dicaffeoylquinic acid (diCQA) isomer 4,5-diCQA exhibits antioxidant activity and various other health-promoting benefits; however, its anti-inflammatory properties require further investigation. This study was conducted to evaluate the anti-inflammatory properties of 4,5-diCQA in vitro and in vivo using RAW264.7 cells and a carrageenan-induced inflammation model, respectively. In RAW264.7 cells, 4,5-diCQA pretreatment significantly inhibited lipopolysaccharide-induced expression of nitric oxide, prostaglandin E2, nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1ß, and interleukin-6, without inducing cytotoxicity. The inhibitory effects of 4,5-diCQA were mediated by the suppression of nuclear factor-κB nuclear translocation and mitogen-activated protein kinase (MAPK) phosphorylation. Oral administration of 4,5-diCQA at doses of 5, 10, and 20 mg/kg of the body weight suppressed carrageenan-induced edema and the expression of nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α in a dose-dependent manner. Collectively, our results suggest that 4,5-diCQA exerts anti-inflammatory effects by suppressing activation of the nuclear factor-κB and MAPK pathways in vitro and reducing carrageenan-induced edema in vivo. Therefore, 4,5-diCQA shows potential as a natural alternative to non-steroidal anti-inflammatory drugs.

Combined antihypertensive effect of unripe Rubus coreanus Miq. and Dendropanax morbiferus H. Lév. Extracts in 1 kidney-1 clip hypertensive rats and spontaneously hypertensive rats.

BACKGROUND: We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored. METHODS: The present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models. RESULTS: The results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta. CONCLUSION: Chronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.

Long-Term Exposure to Urban Particulate Matter on the Ocular Surface and the Incidence of Deleterious Changes in the Cornea, Conjunctiva and Retina in Rats.

We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.

Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Regulates AMPK, SREBP-2, HMGCR, and INSIG-1 Signaling and Cholesterol Metabolism In Vitro and In Vivo.

Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-uRCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5-uRCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-uRCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-uRCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5-uRCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-uRCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-uRCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5-uRCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress.

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.

Longitudinal patterns of social functioning and conversion to psychosis in subjects at ultra-high risk.

OBJECTIVE: Impaired social functioning is one of the defining features of patients with schizophrenia and subjects at ultra-high risk (UHR) for psychosis. This prospective study aimed to investigate the course of social dysfunction in UHR subjects and to examine its relationship with later conversion to psychosis. The effect of pharmacotherapy on the course of social dysfunction was also examined. METHOD: A total of 57 UHR subjects and 58 healthy controls participated in this study. The Social Functioning Scale (SFS) was used to assess social functioning of UHR subjects at baseline and at the 1 year follow up. The changes in social functioning of UHR subjects have been examined to compare the social functioning of those who later converted to psychosis ('converters') with those who did not ('non-converters'). The effect of pharmacotherapy on longitudinal change in social functioning was also evaluated. RESULTS: Subjects at UHR for psychosis showed more impaired social functioning at baseline than did healthy controls. Moreover, the course of social dysfunction of the converter and non-converter groups differed during the 1 year follow up period. The converters showed decreases in SFS average (F (1,32) = 7.85, p = 0.009) and interpersonal behaviour (F (1,32) = 10.43, p = 0.003) scores over time, whereas the non-converters showed increased scores. Additionally, we found that pharmacological treatment was associated with increased prosocial activities score (F (1,32) = 4.66, p = 0.038). CONCLUSIONS: We found that the social functioning of converters was impaired before the onset of the psychosis and further declined during the at-risk phase. A series of social functioning indices in the longitudinal course may be helpful in predicting conversion to psychosis in subjects at UHR. Appropriate pharmacotherapy can offer clinical benefits by improving social functioning in UHR individuals.

What is the optimal dose of escitalopram for the treatment of obsessive-compulsive disorder? A naturalistic open-label study.

This study explored the efficacy and tolerability of very high doses (maximum dose of >40 mg/day), high doses (maximum dose of 25-40 mg/day), and standard doses (maximum dose of ≤20 mg/day) of escitalopram (ESC) as an anti-obsessive-compulsive disorder treatment in a naturalistic clinical setting. We reviewed the medical records of all patients with obsessive-compulsive disorder (n=246) who had taken ESC between May 2006 and September 2009, and assigned Clinical Global Impression (CGI) scores, retrospectively. Of the total sample, 24.4, 38.2, and 37.4% patients received very high, high, and standard doses of ESC, and the mean daily maximum doses of ESC were 57.3±12.0 mg, 33.9±5.4 mg, and 13.4±5.8 mg, respectively. The CGI-Severity scores in each group decreased significantly after treatment with ESC, as evidenced by response rates (i.e. CGI-Improvement scores of 1 or 2) of 46.3, 43.2, and 26.2%, respectively. Although some adverse events increased in a dose-dependent manner, most could be managed with an ESC dose adjustment. These results imply that doses less than or equal to 40 mg/day ESC are sufficient for symptomatic improvement with good tolerability for most patients. Very high doses of ESC, on the other hand, can be considered for patients with inadequate therapeutic responses to the administration of 40 mg/day ESC.

The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.

This study was designed to assess the association between stress, positive affect and catecholamine levels in meditation and control groups. The meditation group consisted of 67 subjects who regularly engaged in mind-body training of "Brain-Wave Vibration" and the control group consisted of 57 healthy subjects. Plasma catecholamine (norepinephrine (NE), epinephrine (E), and dopamine (DA)) levels were measured, and a modified form of the Stress Response Inventory (SRI-MF) and the Positive Affect and Negative Affect Scale (PANAS) were administered. The meditation group showed higher scores on positive affect (p=.019) and lower scores on stress (p<.001) compared with the control group. Plasma DA levels were also higher in the meditation (p=.031) than in the control group. The control group demonstrated a negative correlation between stress and positive affects (r=-.408, p=.002), whereas this correlation was not observed in the meditation group. The control group showed positive correlations between somatization and NE/E (r=.267, p=.045) and DA/E (r=.271, p=.042) ratios, whereas these correlations did not emerge in the meditation group. In conclusion, these results suggest that meditation as mind-body training is associated with lower stress, higher positive affect and higher plasma DA levels when comparing the meditation group with the control group. Thus, mind-body training may influence stress, positive affect and the sympathetic nervous system including DA activity.