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Micheliolide (MCL), a naturally occurring sesquiterpene lactone, has demonstrated significant anticancer properties through the induction of various programmed cell death mechanisms. This study aimed to explore MCL's effects on autophagy, paraptosis, and ferroptosis in pancreatic and colon cancer cells, along with its modulation of the MAPK signaling pathway. MCL was found to substantially suppress cell viability in these cancer cells, particularly in MIA PaCa-2 and HT-29 cell lines. The study identified that MCL induced autophagy by enhancing the levels of autophagy markers such as Atg7, p-Beclin-1, and Beclin-1, which was attenuated by the autophagy inhibitor 3-MA. Furthermore, MCL was found to facilitate paraptosis, indicated by decreased Alix and in-creased ATF4 and CHOP levels. It also promoted ferroptosis, as demonstrated by the reduced expression of SLC7A11, elevated TFRC levels, and increased intracellular iron. Additionally, MCL activated the MAPK signaling pathway, marked by the phosphorylation of JNK, p38, and ERK, linked with an increase in ROS production that is vital in regulating these cell death mechanisms. These findings propose that MCL is a versatile anticancer agent, capable of activating various cell death pathways by modulating MAPK signaling and ROS levels. These results emphasize the therapeutic promise of MCL in treating cancer, pointing to the necessity of further in vivo investigations to confirm these effects and determine its potential clinical uses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Little is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD)., Methods: This multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed., Results: The proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, p = 0.054). In the MOGAD group, the pain score (β=-1.032, p = 0.001) and depression score (β=-0.694, p = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (β=-1.506, p = 0.034) and psychological (β =-2.064, p = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (β=-8.998, p = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain., Conclusions: The overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD., Competing Interests: Declaration of competing interest None of the authors has any potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This retrospective study investigated the influence of palatal fistula (PF) formation after double opposing Z-plasty (DOZ) on speech outcomes in patients with cleft palate (CP), focusing on cleft width and palatal length as predictors of velopharyngeal insufficiency (VPI)., Methods: This study included 1117 patients with CP (579 males, 538 females) who underwent DOZ, performed by a single surgeon, between 1988 and 2017. Demographic characteristics, cleft dimensions, history of PF formation, and speech outcomes were investigated. Speech evaluations were performed at a minimum age of five to assess nasal emission, hypernasality, compensatory articulation, intelligibility, necessity for VPI surgery, and speech therapy. Logistic regression analysis was performed., Results: Speech assessments were conducted at the median age of five (interquartile range [IQR], 5-6 years). Overall, 96.5% of patients achieved 'socially acceptable speech' after DOZ. Patients with PF history showed greater cleft width and experienced higher rates of hypernasality, nasal emission, and VPI on videofluoroscopy (VFS) compared to those without PF history (mean, 11.4 mm vs. 7.1 mm; 28.4% vs. 23.6%; 34.8% vs. 14.9%, 38.5% vs. 14.0%, 40.6% vs. 28.3%, respectively; all p < 0.0001). Cleft width was significantly associated with VPI-related speech outcomes in the multivariate logistic regression analysis, affecting both perceptual and VFS-measured outcomes., Conclusions: A wider CP gap significantly increased the risk of VPI-related speech difficulties after DOZ. Cleft width is a more critical predictor of adverse speech outcomes than the presence of small-to-medium-sized PFs. Patients with a history of PF and wider cleft gaps require targeted interventions and intensified follow-up to effectively manage and improve speech outcomes., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Understanding the ecological characteristics of endangered species is essential for their management and conservation. The dark sleeper ( Odontobutis obscurus ) is a carnivorous freshwater fish that has been designated an endangered species in South Korea because of its highly restricted habitat range and small population size. However, ecological research on prey items for this species remains severely limited globally, posing challenges for establishing conservation measures such as translocation management. In this study, the food sources and feeding strategies of O. obscurus were identified through non-invasive faecal DNA metabarcoding. A total of 24 O. obscurus specimens were collected from Sanyang Stream on Geoje Island, and faecal DNA was amplified using mitochondrial cytochrome c oxidase I (COI) primer. As a result, 13 prey items were identified, comprising fish and benthic invertebrates. Dietary metrics revealed the overall food composition and major food source of O. obscurus , and the Costello method enabled graphical diet analysis, suggesting that O. obscurus is a generalist, feeding on a wide variety of food sources. The food selectivity index suggested that O. obscurus prefers specific prey items, such as genus Misgurnus , Zacco (fish), Radix (gastropod), and Ephemera (mayfly). This molecular method facilitated the diet analysis of an endangered fish species that cannot undergo dissection, providing crucial information for their management, particularly regarding translocation efforts.

Background: There is a lack of evidence of the diagnosis and treatment-related epidemiological studies of symptomatic discoid meniscus. This study analyzed the national epidemiological data for discoid meniscus in South Korea., Methods: From 2011 to 2019, data related to the diagnosis and procedure codes of discoid meniscus were obtained from the Korean Health Insurance Review and Assessment Service database. All patients encoded as discoid meniscus were included. Data were extracted and further analyzed as follows: (1) the total number and the incidence (cases per 100,000) of discoid meniscus diagnosis per year, (2) sex distribution, (3) age distribution, (4) discoid meniscus ratio (total discoid meniscus coding per total meniscus injury coding), and (5) surgical procedures after discoid meniscus injury., Results: The total number of discoid meniscus diagnosed was 4576 in 2011 and increased to 6639 in 2019, representing a 45.1% increase. The incidence was 9.5 in 2011 and increased to 13.0 in 2019. Concerning sex, discoid meniscus was more common in females (55%) than in males (45%) over the study period. Regarding age, the peak age of discoid meniscus in 2011 was "under 19," whereas in 2019, the peak age was observed in the 50s. The discoid meniscus ratio range was 2.12-2.60% from 2011 to 2019. The total number of meniscectomy increased by 20% from 2000 in 2011 to 2475 in 2014. However, the total number of meniscus repairs was 318 in 2011 and increased to 502 in 2019, indicating an increase of 58%., Conclusions: The total number and incidence of symptomatic discoid as well as the discoid meniscus ratio and the incidence of total discoid meniscus repair steadily increased from 2011 to 2019. The number of meniscus repair procedures increased more rapidly than that of meniscectomy. The current study helps understand the epidemiology of symptomatic discoid meniscus, its prevention, and cost-saving measures in South Korea., (© 2024. The Author(s).)

This study aimed to evaluate the enhancement of A. gossypii control by A. colemani when Z. elegans was planted as a companion crop in cucumber greenhouses. The density and spatial distribution of A. gossypii and parasitized mummies were investigated across three treatment plots: (1) the simultaneous application of A. colemani and cultivation of Z. elegans (parasitoid-zinnia plot); (2) the application of A. colemani alone (parasitoid plot); and (3) a control plot (no application of both). A. gossypii maintained low densities in the parasitoid-zinnia plots, while its densities in the parasitoid plots initially decreased but rapidly increased thereafter. The spatial distribution patterns of A. gossypii and parasitized mummies showed similar trends across treatments. However, the parasitism rate of A. gossypii exhibited random distribution in parasitoid and control plots, while showing uniform distribution in the parasitoid-zinnia treatment. These results supported the idea that cultivating Z. elegans alongside cucumber could enhance the effectiveness of A. colemani as a biocontrol agent against A. gossypii , highlighting the importance of such companion planting in pest management strategies.

In marine environments, exposure to microplastics threaten various organisms. A large portion of MPs may be bioavailable to copepods, and ingesting MPs has been reported to induce various adverse effects, including increased mortality, developmental retardation, and decreased reproduction. Adverse effects of MPs on these important processes of copepods may be induced by the obstructive effects of the ingested MPs on energy acquisition. However, few studies have explored the biological effects of MPs on copepods in terms of energy budgets. Therefore, we analyzed ATP (adenosine triphosphate) levels, enzyme activities, swimming distances, and excretion rates in marine copepods (Tigriopus koreanus) that have ingested polystyrene microplastics. Our results indicate that the ingestion of MPs may prevent adequate acquisition of nourishment and lead the copepods into a vicious circle in the respect to energetic burden. Our study provides biochemical evidence for a reduction in the energy budget of copepods due to MPs ingestion. Further, this study increases our understanding of the risks of microplastics, by providing advanced evidences of their effects on marine primary consumer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Longitudinal follow-up data of 1557 patients with cleft palate (CP) was used to identify risk factors for palatal fistula (PF) formation after double-opposing Z-plasty (DOZ), performed by a single surgeon. Overall, 104 (6.7%) of the patients developed PF, all of which were identified within the first month following DOZ. The incidence of PF for clefts of Veau class 1, 2, 3, and 4 was 0%, 6.5%, 4.4%, and 20.3%, respectively. The PFs were pinpoint-shaped in 38.5% of cases, slit-shaped in 40.4% (2-8 mm), and other (10-96 mm 2 ) in 21.1% . Among patients with PF, 14 (13.5%) chose surgical repair; recurrence was observed in four patients, of whom two showed secondary healing. Among the 90 unrepaired cases, 68 (75.6%) showed symptom resolution, mostly within 1-3 years. Recovery varied by PF size category: 81.1% of pinpoint, 71.4% of slit-shaped, and 100% of other fistulas healed spontaneously over a median 9, 3, and 21.5 months, respectively. Multivariate logistic regression analysis identified cleft width as the most significant predictor of PF development (odds ratio 1.25, P < 0.001), while the Veau classification was not a significant determinant. This study identified cleft width as a critical determinant of the risk of PF following DOZ. A conservative strategy that prioritizes symptomatology over PF size (for PFs <1 cm 2 ) is worthy of consideration., Competing Interests: Competing interests None., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 10 7 hUC-O cells, n = 3), medium-dose (2 × 10 7 cells, n = 3), and high-dose group (4 × 10 7 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

Northeast Asia suffers from high concentrations of particulate matter (PM), prompting nations to actively implement emission reduction policies. This study evaluated the recent inter-annual changes in the chemical transformation and transboundary transport of PM over Northeast Asia, based on both ground and aircraft measurements, as well as WRF-Chem simulations, during two comprehensive campaigns: the Korea-United States Air Quality (KORUS-AQ) campaign in 2016 and the Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) campaign in 2022, both conducted around the Korean Peninsula. Ground measurements in 2022 revealed significant reductions in air pollutants compared to 2016 levels. In the Beijing-Tianjin-Hebei region, PM 2.5 and SO 2 concentrations decreased by 47.2% and 73.9%, respectively, attributable to successful SO x and NO x emission reduction strategies. Similar trends were observed in downwind areas, including Seoul, where PM 2.5 and SO 2 levels declined by 30.0% and 41.4%, respectively. WRF-Chem model results indicated substantial decreases in sulfates, nitrates, and their precursors in both surface and upper atmosphere in 2022 compared to 2016. Moreover, model-calculated gas-to-particle conversion ratios, which peaked in the Yellow Sea in 2016, decreased by 15% in 2022 and shifted slightly eastward to the western Korean Peninsula. This shift suggests a potential decline in secondary PM formation processed in the Yellow Sea, coinciding with reduced long-range transport of gaseous pollutants. A comparison of model sensitivity experiments, accounting for both bottom-up emission changes and meteorological variations, revealed that while weather and climate factors such as precipitation and pressure patterns between 2016 and 2022 contributed to the overall decrease in PM concentrations, the primary driver was the reduction in emissions during this period. This study highlighted that the main driver of the substantial improvement in air quality over East Asia was the implementation of emission reduction policies targeting PM and its precursors in the main source regions in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Marine plastic debris (MPD) is a potential threat to marine ecosystems, but its function as a vector for the transportation of harmful microalgae and its impact on the habitats of other marine organisms are uncertain. To address this gap in knowledge, we performed month-long experiments in 30 L microcosms that contained plates made of six different plastic polymers (polypropylene [PP], low-density polyethylene [LDPE], high-density polyethylene [HDPE], polyvinyl chloride [PVC], polyethylene terephthalate [PET], and polystyrene [PS]), and examined the time course of changes in planktonic and periphytic microalgae. There were no significant differences in the composition of periphytic microalgae or biomass among the different plastic polymers (p > 0.05). Nutrient depletion decreased the abundance of planktonic microalgae, but increased the biomass of attached periphytic microalgae (p < 0.05). In particular, analysis of the plastic plates showed that the abundance of benthic species that are responsible for harmful algal blooms (HABs), such as Amphidinium operculatum and Coolia monotis, significantly increased over time (days 21-28; p < 0.05). Our findings demonstrated that periphyton species, including benthic microalgae that cause HABs, can easily attach to different types of plastic and potentially spread to different regions and negatively impact these ecosystems. These observations have important implications for understanding the potential role of MPD in the spread of microalgae, including HABs, which pose a significant threat to marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The neurotoxin β-N-methylamino-L-alanine (BMAA), produced by cyanobacteria and diatoms, has been implicated as an environmental risk factor for neurodegenerative diseases. This study first investigated the occurrence and monthly distributions of BMAA and its isomers, 2,4-diaminobutyric acid (DAB) and N-2-aminoethylglycine (AEG), in phytoplankton and mussels from 11 sites along the South Sea Coast of Korea throughout 2021. These toxins were quantified using LC-MS/MS, revealing elevated BMAA concentrations from late autumn to spring, with phase lags observed between phytoplankton and mussels. The highest concentration of BMAA in phytoplankton was detected in November (mean: 1490 ng g -1 dry weight (dw)), while in mussels, it peaked in December (mean: 1240 ng g -1 dw). DAB was detected in phytoplankton but was absent in mussels, indicating limited bioaccumulation potential. In February, the peak mean DAB concentration in phytoplankton was 89 ng g -1 dw. AEG was not detected in any samples. Chlorophyll-a concentrations consistently showed an inverse correlation with BMAA concentrations in mussels throughout the year. Through correlation analysis, four diatom genera, Bacillaria, Hemiaulus, Odontella, and Pleurosigma, were identified as potential causative microalgae of BMAA. This study offers insights into identifying the causative microalgae for BMAA and informs future regulatory efforts regarding unmanaged biotoxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head., Methods: A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0-34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0-20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×10 7 (IQR, 9.9-10.9 ×10 7 ). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS)., Results: The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) ( p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last follow-up ( p = 0.072 and p = 0.635, respectively)., Conclusions: Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weight-bearing areas., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

In this study, lipophilic marine algal toxins (LMATs)-producing microalgae were identified at 23 sites along the coasts of Korea, and distribution characteristics of LMATs in phytoplankton and mussels were investigated. The causative microalgae, including Gonyaulux spinifera, Dinophysis acuminata, D. caudata, and D. fortii, were observed in the study area, with notably higher densities during the summer. Significant correlations were found between the densities of these microalgae and the water temperature. Seasonal distribution patterns of LMATs in phytoplankton closely matched those observed in mussels. Notably, LMAT concentrations in mussels from the Yellow Sea were relatively high. PTX2 was detected predominantly in phytoplankton, and homo-yessotoxin was found mainly in mussels. Overall, LMAT concentrations were elevated in the summer, raising concerns about biotoxin contamination in shellfish. These results provide important insights into the dynamics of unmanaged marine biotoxins in Korea and offer baseline data for future safety management policies and inflow surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study investigates the growth characteristics of Salmonella enteritidis ( S. enteritidis ) in liquid whole egg under both isothermal and non-isothermal storage conditions to understand the risks associated with inadequate temperature management in the egg industry. Using controlled laboratory simulations, liquid whole egg samples inoculated with S. enteritidis were stored under various isothermal (5, 15, 25, 35, and 45 °C) and non-isothermal conditions (5-10, 15-20, 25-30, 35-40, and 45-50 °C). The growth behavior of the S. enteritidis was analyzed using a two-step predictive modeling approach. First, growth kinetic parameters were estimated using a primary model, and then the effects of temperature on the estimated specific growth rate and lag time were described using a secondary model. Independent growth data under both isothermal and non-isothermal conditions were used to evaluate the models. The results showed that S. enteritidis exhibits different growth characteristics depending on temperature conditions, emphasizing the need for strict temperature control to prevent foodborne illnesses. To address this, a predictive growth model tailored for non-isothermal conditions was developed and validated using experimental data, demonstrating its reliability in predicting S. enteritidis behavior under dynamic temperature scenarios. Additionally, temperature management technologies were proposed and tested to improve food safety during refrigerated storage. This study provides a scientific basis for improving food safety protocols in the egg industry, thereby protecting public health and maintaining consumer confidence amid temperature fluctuations.

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal genes, thereby diminishing histone H3K27 acetylation, restricting chromatin accessibility, and downregulating lysosomal gene expression. Under starvation, USF2 competes with transcription factor EB (TFEB), a master transcriptional activator of lysosomal and autophagy genes, to bind to target gene promoters in a phosphorylation-dependent manner. The GSK3β-mediated phosphorylation of the USF2 S155 site governs USF2 DNA-binding activity, which is involved in lysosomal gene repression. These findings have potential applications in the treatment of protein aggregation-associated diseases, including α1-antitrypsin deficiency. Notably, USF2 repression is a promising therapeutic strategy for lysosomal and autophagy-related diseases., (© 2024. The Author(s).)

The overproduction of proinflammatory cytokines triggers a variety of diseases. Protopanaxadiol (PPD) and resveratrol are naturally found in plants such as ginseng and have potential anti-inflammatory properties, and resveratrol- and PPD-enriched rice seeds have been previously successfully generated. Herein, the synergistic anti-inflammatory activities of extracts of these enriched seeds were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In comparison with treatment using extract prepared from PPD-producing transgenic rice (DJ-PPD) alone, cotreatment with DJ526 and DJ-PPD (TR&#95;3) markedly enhanced the anti-inflammatory activities at a similar (compared to DJ526) or higher (compared to DJ-PPD) level. Cotreatment with DJ526 and DJ-PPD markedly inhibited the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Thus, DJ526 and DJ-PPD in combination suppressed the expression of phosphorylated (p)-NF-κB p65, p-p38 MAPK, and p-ERK 1/2. Cotreatment with DJ526 and DJ-PPD downregulated the expression of proinflammatory cytokines ( IL-1β , IL-6 , and TNF-α ), LPS receptor (toll-like receptor-4, TLR-4 ), proinflammatory mediators (nitric oxide and PGE 2 ), and arachidonic acid pathway critical enzyme ( COX-2 ). These findings demonstrate the synergistic potential anti-inflammatory activities of resveratrol- and PPD-enriched rice seed extract.

Background: Ultrafiltration with continuous kidney replacement therapy (CKRT) can be used to manage fluid balance in critically ill patients with acute kidney injury (AKI). We aimed to assess whether bioimpedance analysis (BIA)-guided volume management was more efficacious than conventional management for achieving estimated euvolemia (e-euvolemia) in CKRT-treated patients., Methods: In a multi-center randomized controlled trial from July 2017 to July 2020, the patients with AKI requiring CKRT were eligible if the weight at the start of CKRT had increased by ≥5% compared to the weight at the time of admission, or total body water (TBW)/ height (H)2 ≥13 L/m2. We randomly assigned 208 patients to the control (conventional fluid management; N=103) and intervention groups (BIA-guided fluid management; N=105). Primary outcome was the proportion of attaining e-euvolemia seven days post-randomization. E-euvolemia was defined as the difference between TBW/H2 D7 and D0 was <-2.1 L/m2, or when TBW/H2 measured on D7 was <13 L/m2. The 28-, 60-, and 90-day mortality rate were secondary outcomes., Results: The primary outcome occurred in 34 patients in the intervention group and 27 in the control group (47% versus 41%; P=0.50). The mean value of TBW/H2 measured on D7 was the same at 13.9 L/m2 in both groups. The differences between TBW/H2 D7 and D0 were -1.13 L/m2 in the intervention group and -1.08 L/m2 in the control group (P=0.84). Patients in the intervention group had a significantly higher proportion of reaching e-euvolemia on D1 than those in the control group (13% versus 4%, P=0.02). Adverse events did not differ significantly between the groups., Conclusions: BIA-guided volume management did not affect the proportion of reaching the estimated euvolemia at seven days of the start of CKRT., Trial Registration: ClinicalTrials.gov, ID: NCT03330626 (Registered on 6 November 2017; Seven study participants were retrospectively registered; nonetheless, IRB approval of each institution was completed before study participant registration)., (Copyright © 2024 by the American Society of Nephrology.)

The widespread use of single-use face masks during the recent epidemic has led to significant environmental challenges due to waste pollution. This study explores an innovative approach to address this issue by repurposing discarded face masks for hydrovoltaic energy harvesting. By coating the face masks with carbon black (CB) to enhance their hydrophilic properties, we developed mask-based hydrovoltaic power generators (MHPGs). These MHPGs were evaluated for their hydrovoltaic performance, revealing that different mask configurations and sizes affect their efficiency. The study found that MHPGs with smaller, more structured areas exhibited better energy output, with maximum open-circuit voltages ( V OC ) reaching up to 0.39 V and short-circuit currents ( I SC ) up to 65.6 μA. The integration of CB improved water absorption and transport, enhancing the hydrovoltaic performance. More specifically, MHPG-1 to MHPG-4, which represented different sizes and features, presented mean V OC values of 0.32, 0.17, 0.19 and 0.05 V, as well as mean I SC values of 16.57, 15.59, 47.43 and 3.02 μA, respectively. The findings highlight the feasibility of utilizing discarded masks in energy harvesting systems, offering both environmental benefits and a novel method for renewable energy generation. Therefore, this work provides a new paradigm for waste-to-energy (WTE) technologies and inspires further research into the use of unconventional waste materials for energy production.

Leaf senescence is a crucial process throughout evolution, vital for plant fitness as it facilitates the gradual shift of energy allocation between photosynthesis and catabolism overtime. This onset is influenced by a complex interplay of genetic and environmental factors, making senescence a key adaptation mechanism for plants in their natural habitats. Our study investigated the genetic mechanism underlying age-induced leaf senescence in Arabidopsis natural populations. Using a phenome high-throughput investigator, we comprehensively analyzed senescence responses across 234 Arabidopsis accessions and identified that environmental factors (e.g., ambient temperature) and physiological factors (e.g., defense responses) are substantially linked to senescence phenotypes. Through genome-wide association mapping, we identified the ACCELERATED CELL DEATH 6 (ACD6) locus as a potential regulator of senescence variation among natural accessions. Knocking out ACD6 in accessions with early and delayed senescence phenotypes resulted in varying degrees of delay in age-induced senescence, highlighting the accession-dependent regulatory role of ACD6 in leaf senescence. Furthermore, our findings suggest ACD6's involvement in senescence regulation via the salicylic acid signaling pathway. In summary, our study sheds light on the genetic regulation of leaf senescence in Arabidopsis natural populations, with the discovery of ACD6 as a potential candidate for genetic modification to enhance plant adaptation and survival., (© 2024 Scandinavian Plant Physiology Society.)

This study aimed to determine the optimal injection dose for non-human primate positron emission tomography (PET). We first used a monkey brain phantom with a volume of 80,000 mm 3 containing 250 MBq of [ 18 F]FDG. Next, we compared the radioactivity difference between the PET images and the actual radioactivity from the dose calibrator to determine the low-error range. We then evaluated the image quality using the NEMA-NU phantom. Finally, [ 18 F]FP-CIT PET images were obtained from two monkeys with middle and high doses. As a result, PET images with a middle injected dose generated reasonable image quality and showed a high signal-to-noise ratio in monkey brain PET with [ 18 F]FP-CIT. These results are expected to be actively applied in PET research using non-human primates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immunotherapy combined with chemicals and genetic engineering tools is emerging as a promising strategy to treat triple-negative breast cancer (TNBC), which is more aggressive with poorer progress than other breast cancer subtypes. In this study, lipid-based nanoparticles (LNPs) possessed an NK cell-like function that could deliver tumor-specific therapeutics and inhibit tumor growth. LNPs fused with an NK cell membrane protein system (NK-LNP) have three main features: (i) hydrophilic plasmid DNA can inhibit TNBC metastasis when encapsulated within LNPs and delivered to cells; (ii) the lipid composition of LNPs, including C18 ceramide, exhibits anticancer effects; (iii) NK cell membrane proteins are immobilized on the LNP surface, enabling targeted delivery to TNBC cells. These particles facilitate the targeted delivery of HIC1 plasmid DNA and the modulation of immune cell functions. Delivered therapeutic genes can inhibit metastasis of TNBC and then induce apoptotic cell death while targeting macrophages to promote cytokine release. The anticancer effect is expected to be applied in treating various difficult-to-treat cancers with LNP fused with NK cell plasma membrane proteins, which can simultaneously deliver therapeutic chemicals and genes.

Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16 -/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16 -/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury., Competing Interests: Declaration of interests The authors declare that no potential conflicts of interest exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cachexia and sarcopenia are common among heart failure (HF) patients and are linked to poor outcomes. As serum creatinine levels are influenced by both renal function and muscle mass, our study aimed to investigate the relationship between serum creatinine levels and mortality in acute HF patients., Methods: We enrolled 5198 consecutive acute HF patients from the Korea Acute Heart Failure (KorAHF) registry, excluding those on renal replacement therapy. Patients were categorized into five groups based on their discharge serum creatinine levels: low (< 0.6 mg/dL), reference (0.6-0.89 mg/dL), upper normal (0.9-1.19 mg/dL), high (1.2-1.49 mg/dL), and very high (≥ 1.5 mg/dL). The primary endpoint was post-discharge all-cause mortality., Results: The mean creatinine level was 1.20 ± 0.88 mg/dL. Notably, 335 (6.4%) patients had serum creatinine levels < 0.6 mg/dL. These patients were younger (mean age, 67 years) and more likely to have a low BMI (< 18.5 kg/m 2 ) compared to the reference group (15.3% vs. 6.4%). Over a median follow-up of 975 days, 1743 (34.8%) patients died. We observed a J-shaped relationship between serum creatinine levels and mortality, with both low and high levels associated with increased mortality. After adjusting for covariates, including age, sex, body mass index, diabetes, hypertension, smoking, malignancy, atrial fibrillation on electrocardiography, levels of C-reactive protein, sodium, hemoglobin, albumin, brain natriuretic peptide, de novo heart failure, use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists, patients with serum creatinine levels < 0.6 mg/dL had a 33% higher risk of all-cause mortality (HR, 1.33; 95% CI, 1.06 to 1.66) compared to those with levels of 0.6-0.89 mg/dL. However, BUN, which is not affected by muscle metabolism, exhibited a linear relationship with mortality., Conclusions: Among acute HF patients, there exists a J-shaped relationship between discharge serum creatinine levels and mortality, highlighting the increased mortality risk in individuals with very low serum creatinine levels., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4 + T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety., (© 2024. The Author(s).)

Traditional herbal medicines (THMs) have long been in use worldwide and are considered safe for use as tonics or complementary treatments for many diseases. Advanced quality control methods for THMs are required in the regulatory framework of modern medicines. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry assay was established for the simultaneous determination of 22 marker compounds in Ojeoksan (OJS), which is composed of 15 herbal substances. All marker compounds were analyzed within 20 min and successfully identified via scheduled multiple reaction monitoring. The method validation revealed excellent performance characteristics of the method such as specificity, linearity, sensitivity, precision, and accuracy, demonstrating its suitability for intended use. The developed method was applied to samples of commercial OJS tablet and soft-extract dosage forms. The 14 marker compounds corresponding to 12 component herbal substances were determined in the samples; ephedirine, albiflorin, paeoniflorin, ferulic acid, hesperidine, neohesperidin, cinnamic acid, platycodin D, 6-gingerol, atractylenolide III, glycyrrhizin, honokiol, decursin, and magnolol. A fast and easy assay method with sufficient discrimination power was established. As a novel assay, this method can contribute to the quality control of OJS products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H 2 O 2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H 2 O 2 ) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4 , ADAMTS-5 , MMP3 , and MMP13 , key genes involved in NP degeneration. While H 2 O 2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.

Liquid-liquid phase separation (LLPS) facilitates the formation of membraneless organelles within cells, with implications in various biological processes and disease states. AT-rich interactive domain-containing protein 1A (ARID1A) is a chromatin remodeling factor frequently associated with cancer mutations, yet its functional mechanism remains largely unknown. Here, we find that ARID1A harbors a prion-like domain (PrLD), which facilitates the formation of liquid condensates through PrLD-mediated LLPS. The nuclear condensates formed by ARID1A LLPS are significantly elevated in Ewing's sarcoma patient specimen. Disruption of ARID1A LLPS results in diminished proliferative and invasive abilities in Ewing's sarcoma cells. Through genome-wide chromatin structure and transcription profiling, we identify that the ARID1A condensate localizes to EWS/FLI1 target enhancers and induces long-range chromatin architectural changes by forming functional chromatin remodeling hubs at oncogenic target genes. Collectively, our findings demonstrate that ARID1A promotes oncogenic potential through PrLD-mediated LLPS, offering a potential therapeutic approach for treating Ewing's sarcoma., (© 2024. The Author(s).)

The process of apoptosis is one of the essential processes involved in maintenance of homeostasis in the human body. It can aid to remove misfolded proteins or cellular organelles. This sequence is especially necessary in cancer cells. However, specifically targeting already apoptotic pathways can induce drug resistance in cancer cells and hence drugs can induce cell death by alternative mechanism. We investigated whether fangchinoline (FCN) can target renal carcinoma cells by inducing multiple cell death mechanisms. Both paraptosis, autophagy, and apoptosis were induced by FCN through stimulation of diverse molecular signaling pathways. FCN induced ROS production with GSH/GSSG imbalance, and ER stress. In addition, formation of autophagosome and autophagy related markers were stimulated by FCN. Moreover, FCN induced cell cycle arrest and PARP cleavage. Except for blocking protein synthesis, these three cell death pathways were found to be complementarily working together with each other. FCN also exhibited synergistic effects with paclitaxel in inducing programmed cell death in RCC cells. Our data indicates that FCN could induce apoptotic cell death and non-apoptotic cell death pathways and can be con-tribute to development of novel cancer prevention or therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the accuracy of artificial intelligence-assisted growth prediction using a convolutional neural network (CNN) algorithm and longitudinal lateral cephalograms (Lat-cephs)., Materials and Methods: A total of 198 Japanese preadolescent children, who had skeletal Class I malocclusion and whose Lat-cephs were available at age 8 years (T0) and 10 years (T1), were allocated into the training, validation, and test phases (n = 161, n = 17, n = 20). Orthodontists and the CNN model identified 28 hard-tissue landmarks (HTL) and 19 soft-tissue landmarks (STL). The mean prediction error values were defined as 'excellent,' 'very good,' 'good,' 'acceptable,' and 'unsatisfactory' (criteria: 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively). The degree of accurate prediction percentage (APP) was defined as 'very high,' 'high,' 'medium,' and 'low' (criteria: 90%, 70%, and 50%, respectively) according to the percentage of subjects that showed the error range within 1.5 mm., Results: All HTLs showed acceptable-to-excellent mean PE values, while the STLs Pog', Gn', and Me' showed unsatisfactory values, and the rest showed good-to-acceptable values. Regarding the degree of APP, HTLs Ba, ramus posterior, Pm, Pog, B-point, Me, and mandibular first molar root apex exhibited low APPs. The STLs labrale superius, lower embrasure, lower lip, point of lower profile, B', Pog,' Gn' and Me' also exhibited low APPs. The remainder of HTLs and STLs showed medium-to-very high APPs., Conclusion: Despite the possibility of using the CNN model to predict growth, further studies are needed to improve the prediction accuracy in HTLs and STLs of the chin area., (© 2024 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

Background: Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH., Methods: A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0 years [interquartile range (IQR), 28.5-42.0], and the median follow-up period was 4.0 years (IQR, 2.0-5.3). The median number of MSCs was 1.06 × 10 8 . To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up., Results: The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips., Conclusion: CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH., (© 2024. Korean Tissue Engineering and Regenerative Medicine Society.)

Background: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae., Methods: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis., Results: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION., Conclusion: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON., Competing Interests: Competing interests: S-MK has lectured, consulted and received honoraria from Bayer Schering Pharma, Genzyme, Merck Serono and UCB; and received a grant from the National Research Foundation of Korea and the Korea Health Industry Development Institute Research. S-MK and KSP are associate editors of the Journal of Clinical Neurology. S-MK, KSP, Seoul National University and Seoul National University Hospital have transferred the technology of the flow cytometric autoantibody assay to the EONE Laboratory, Korea., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Bovine mastitis (BM) has caused huge economic and financial losses in the dairy industry worldwide, with Staphylococcus aureus as one of its major pathogens. BM treatment still relies on antibiotics and its extensive use often generates methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. aureus (MuRSA). This study compared the antimicrobial resistance trend in coagulase-positive Stapholococci (CoPS) isolated from BM milk in conventional and organic dairy farms and checked prevalence of MRSA and MuRSA. A total of 163 presumptive Staphylococci were isolated, wherein 11 out of 74 from 4 conventional farms (CF1, CF2, CF3, CF4) and 17 out of 89 from 3 organic farms (OF1, OF2, OF3) exhibited coagulase activity. Multiplex-PCR amplification confirmed at least one coagulase-positive isolate from CF1, CF2, CF3, CF4, and OF1 as S. aureus , denoted by the presence of the nuc gene. Three isolates from CF2 contained the mecA gene, indicating MRSA prevalence, while the MuRSA gene marker, mupA , was not detected in any of the isolates. Antimicrobial testing showed that conventional farm isolates were more resistant to antibiotics, especially ampicillin and tetracycline. This suggests a risk of developing multidrug resistance in dairy farms if antibiotic use is not properly and strictly monitored and regulated.

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis ( p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns ( p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

Competing Interests: Byung-Jo Kim, the Editor-in-Chief of the Journal of Clinical Neurology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest.

Background: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension., Methods: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment., Results: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m 2 ; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m 2 . Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients., Conclusion: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients., (© 2024. The Author(s).)

Analyzing the concentration of ions in aqueous solutions in real-time plays an important role in the fields of chemistry and biology. Traditional methods for measuring ion concentrations, such as concentration analysis by measuring electrical conductivity, inductively coupled plasma mass spectrometry, and ion chromatography, have been used in many research fields. However, these methods are limited in determining ion concentrations instantaneously. Fourier-transform infrared-attenuated total reflectance (ATR-FTIR) spectroscopy provides a new approach for determining ion concentrations in aqueous solutions. This allows for fast analysis without pretreatment and is scalable for real-time measurements. In this study, we present a method for measuring ion concentrations by examining ion-water interactions in the O-H stretching band of aqueous solutions using ATR-FTIR spectroscopy. Five aqueous solutions, namely LiCl + HCl, LiOH + HCl, LiOH, Li 3 PO 4 , and NaCl were used in the experiments and prepared at concentrations between 0.5-2 M. The ion concentrations in the prepared aqueous solutions were measured using ATR-FTIR spectroscopy. We observed that the difference in absorbance increased and decreased linearly with changes in concentration. The concentration of ions in the aqueous solution could be measured by validating the designed linear regression analysis function model. In this study, we proposed five linear regression analysis function models, all of which showed high coefficients of determination above 0.9, with the highest coefficient of determination reaching 0.9969. These results show that ATR-FTIR spectroscopy has the potential to be applied as a rapid and simple concentration analysis system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Various environmental factors play a role in the formation and collapse of Microcystis blooms. This study investigates the impact of heavy rainfall on cyanobacterial abundance, microbial community composition, and functional dynamics in the Nakdong River, South Korea, during typical and exceptionally rainy years. The results reveal distinct responses to rainfall variations, particularly in cyanobacterial dominance and physicochemical characteristics. In 2020, characterized by unprecedented rainfall from mid-July to August, Microcystis blooms were interrupted significantly, exhibiting lower cell densities and decreased water temperature, compared to normal bloom patterns in 2019. Moreover, microbial community composition varied, with increases in Gammaproteobacteria and notably in genera of Limnohabitans and Fluviicola. These alterations in environmental conditions and bacterial community were similar to those of the post-bloom period in late September 2019. It shows that heavy rainfall during summer leads to changes in environmental factors, consequently causing shifts in bacterial communities akin to those observed during the autumn-specific post-bloom period in typical years. These changes also accompany shifts in bacterial functions, primarily involved in the degradation of organic matter such as amino acids, fatty acids, and terpenoids, which are assumed to have been released due to the significant collapse of cyanobacteria. Our results demonstrate that heavy rainfall in early summer induces changes in the environmental factors and subsequently microbial communities and their functions, similar to those of the post-bloom period in autumn, leading to the earlier breakdown of Microcystis blooms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rapeseed ( Brassica napus L.) holds significant commercial value as one of the leading oil crops, with its agronomic features and oil quality being crucial determinants. In this investigation, 73,226 single nucleotide polymorphisms (SNPs) across 95 rapeseed mutant lines induced by gamma rays, alongside the original cultivar ('Tamra'), using genotyping-by-sequencing (GBS) analysis were examined. This study encompassed gene ontology (GO) analysis and a genomewide association study (GWAS), thereby concentrating on agronomic traits (e.g., plant height, ear length, thousand-seed weight, and seed yield) and oil traits (including fatty acid composition and crude fat content). The GO analysis unveiled a multitude of genes with SNP variations associated with cellular processes, intracellular anatomical structures, and organic cyclic compound binding. Through GWAS, we detected 320 significant SNPs linked to both agronomic (104 SNPs) and oil traits (216 SNPs). Notably, two novel candidate genes, Bna.A05p02350D (SFGH) and Bna.C02p22490D (MDN1), are implicated in thousand-seed weight regulation. Additionally, Bna.C03p14350D (EXO70) and Bna.A09p05630D (PI4Kα1) emerged as novel candidate genes associated with erucic acid and crude fat content, respectively. These findings carry implications for identifying superior genotypes for the development of new cultivars. Association studies offer a cost-effective means of screening mutants and selecting elite rapeseed breeding lines, thereby enhancing the commercial viability of this pivotal oil crop.

The purpose of this study was to compare speech outcomes in patients with submucous cleft palate (SMCP) between speech therapy alone and double-opposing Z-plasty (DOZ) combined with speech therapy. The subjects were 67 patients with SMCP (overt type, 45 males, 22 females), who were divided into the observation group (n=18), the speech therapy group (n=24; duration, 17.8 mo), and the DOZ and speech therapy (DOZ-speech therapy) group (n=25; median age at DOZ, 5.3 years, duration, 18.6 mo). The median age at initial and final speech assessments were 3 and 5 years. After age, sex, syndromic status, duration of speech therapy, surgery timing, and speech outcomes were investigated, statistical analysis was performed. After tailored interventions, both isolated and non-isolated SMCP patients experienced significant improvements in speech outcomes, including nasal emission, hypernasality, compensatory articulation, and unintelligible speech. Since comparable improvements were observed, there were no significant differences in the final assessments regardless of initial speech issues between the speech therapy group and the DOZ-speech therapy group (all P>0.05). In the DOZ-speech therapy group, the rate of achieving "socially acceptable" speech was 92.3% in isolated cases and 90% in non-isolated cases. Multivariate analysis revealed that DOZ showed a tendency to reduce hypernasality, compensatory articulation, and "unintelligible" speech; syndromic or developmental conditions influenced outcomes in nasal emission and hypernasality; and initial hypernasality and compensatory articulation were correlated with outcomes. Therefore, DOZ surgery could be recommended to resolve hypernasality and compensatory articulation in SMCP patients before speech issues worsen., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Purpose: Epidemiological evidence shows that physical activity, including continuous stimulus changes and appropriate exercise programs, improves brain degeneration in the hippocampus, prefrontal cortex (PFC), and anterior cingulate cortex (ACC). Therefore, we investigated the possible synergistic effects of physical activity and nutrition in controlling chronic fatigue and reducing oxidative stress in patients at risk for depression and suicide., Methods: We systematically reviewed the literature on various systemic factors related to the effects of 1) suppressing oxidative stress and 2) improving depression through exercise and nutrition. To conduct this review, we searched the PubMed database for papers published until May 1, 2024, using the terms "physical activity OR exercise" and "fatigue" OR "anti-fatigue," "oxidative stress" and "depression" and "suicide." We then reviewed the resulting list of articles related to antioxidant mechanisms., Results: Appropriate physical activity and natural product intake can substantially change whole-body homeostasis and provide a way to overcome the threat of depression and suicide by regulating metabolites, scavenging free radicals, and neurotransmitters., Conclusion: Suicide and depression prevention play crucial roles in improving patients' quality of life. Our review provides evidence supporting the idea that exercise and antioxidant nutrition diminish oxidative stress and fatigue by improving the degeneration of the hippocampus, PFC, and ACC.

Background: Computer-assisted navigation surgery (CAS) during primary total knee arthroplasty (TKA) may help improve outcomes for patients with extra-articular deformity (EAD); however, this has not been extensively studied. Therefore, we aimed to investigate the clinical and radiological outcomes following primary TKA using CAS in patients with EAD., Methods: We searched Medline, Embase, and the Cochrane Library up to March 3, 2023 for studies investigating surgical outcomes of using the navigation system for TKA to treat patients with EAD. From 14 studies, 539 knees with EAD that underwent navigation TKA were enrolled. We investigated the knee range of motion (ROM), outcome scores at final follow-up (Knee Society Score [KSS] and Knee Functional Score [KFS]), and pre- and postoperative mechanical hip-knee-ankle (mHKA) angle using lower extremity scanogram. The meta-analysis was based on the single-arm method, and all data were pooled using a random-effects model., Results: Following our meta-analyses, the mean knee ROM changed from 87.0° (95% confidence interval [CI], 75.9°-98.1°) preoperatively to 109.4° (95% CI, 97.9°-120.8°) postoperatively. The adjusted KSS was 93.45 points (95% CI, 88.36-98.54 points), and the adjusted KFS was 91.57 points (95% CI, 86.80-96.33 points) in knees with EAD that underwent CAS-TKA. As a radiological outcome, the mHKA angle changed from 169.53° (95% CI, 166.90°-172.16°) preoperatively to 178.81° (95% CI, 178.31°-179.30°) postoperatively., Conclusions: CAS-TKA yielded positive clinical results and demonstrated a satisfactory alignment of the lower limb's mechanical axis. CAS-TKA showed promise for primary TKA procedures, demonstrating favorable clinical and radiological outcomes even in complex cases involving EAD., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

The excessive production of melanin can cause skin diseases and hyperpigmentation. In this study, resveratrol contained in Dongjin rice seed (DJ526) was increased through callus induction. The antioxidant capacity of resveratrol-enriched rice callus was evaluated using the ABTS radical scavenging method and was equivalent to that of vitamin C. DJ526 rice callus extract significantly increased antioxidant activities in a concentration-dependent manner. The anti-melanogenesis effects of DJ526 rice callus extract were also evaluated in melan-a cells. Resveratrol-enriched rice callus extract significantly (i) decreased the size and number of melanin-containing cells, (ii) suppressed the activity of cellular tyrosinase and melanin content, (iii) downregulated the expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, (iv) increased the expression of phosphorylated extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) inhibited the activation of phosphorylated p38 in melan-a cells. From the above observations, DJ526 rice callus extract showed strong antioxidant and anti-melanogenesis activity at the concentration test. These findings indicate the potential of resveratrol-enriched rice callus as a novel agent for controlling hyperpigmentation.

Objective: To investigate the growth patterns of the maxillomandibular complex in preadolescent patients with Pierre-Robin sequence (PRS)., Methods: The samples consisted of 20 preadolescent PRS patients who had cleft palate and did not undergo growth-modification therapy or surgical intervention [6 boys and 14 girls; mean age of lateral cephalograms taken, 8.8 y (T1) and 13.7 y (T2)]. According to k-means cluster analysis, four clusters were defined over 3 major groups at T1: (1) Both very retrusive maxilla and mandible group: Cluster-4 [n=4, very large gonial angle, very low facial height ratio (FHR)] and Cluster-1 (n=5, small gonial angle, normal FHR); (2) Retrusive maxilla and very retrusive mandible group (Cluster-3, n=7, normal gonial angle, very low FHR); and (3) Both normal maxilla and mandible group (Cluster-2, n=4, very large gonial angle, low FHR). Seven angular and ratio variables [sella-nasion-A point (SNA), sella-nasion-B point (SNB), A point-nasion-B point (ANB), saddle angle, gonial angle, mandibular-body-length/anterior-cranial-base-length (MBL/ACBL), and FHR] at T1 and T2 and growth change from T1 to T2 were investigated., Results: At T1, SNA, SNB, saddle angle, gonial angle (all P<0.05), and FHR (P<0.01) showed significant difference among 4 clusters. At T2, SNA, SNB and gonial angle (all P<0.05) still showed significant difference among 4 clusters. During T1 to T2, there was no significant change in variables at each cluster except an increase in MBL/ACBL in Cluster-1 and FHR in Cluster-3 (all P<0.05)., Conclusions: Preadolescent PRS patients exhibited diverse skeletal phenotypes at T1, which did not change significantly from their original skeletal patterns by growth during T1 to T2., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea., Methods: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients., Results: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized ( P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients ( P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients ( P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients., Conclusion: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background : Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods : Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results : A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions : Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

Osteoarthritis is the most prevalent type of degenerative arthritis. It is characterized by persistent pain, joint dysfunction, and physical disability. Pain relief and inflammation control are prioritised during osteoarthritis treatment Mume Fructus (Omae), a fumigated product of the Prunus mume fruit, is used as a traditional medicine in several Asian countries. However, its therapeutic mechanism of action and effects on osteoarthritis and articular chondrocytes remain unknown. In this study, we analyzed the anti-osteoarthritis and articular regenerative effects of Mume Fructus extract on rat chondrocytes. Mume Fructus treatment reduced the interleukin-1β-induced expression of matrix metalloproteinase 3, matrix metalloproteinase 13, and a disintegrin and metalloproteinase with thrombospondin type 1 motifs 5. Additionally, it enhanced collagen type II alpha 1 chain and aggrecan accumulation in rat chondrocytes. Furthermore, Mume Fructus treatment regulated the inflammatory cytokine levels, mitogen-activated protein kinase phosphorylation, and nuclear factor-kappa B activation. Overall, our results demonstrated that Mume Fructus inhibits osteoarthritis progression by inhibiting the nuclear factor-kappa B and mitogen-activated protein kinase pathways to reduce the levels of inflammatory cytokines and prevent cartilage degeneration. Therefore, Mume Fructus may be a potential therapeutic option for osteoarthritis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)