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Hyunseong Kim,1 Jin Young Hong,1 Wan-Jin Jeon,1 Junseon Lee,1 Seung Ho Baek,2 In-Hyuk Ha1 1Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896, Republic of Korea; 2College of Korean Medicine, Dongguk University, Goyang-si, 10326, Republic of KoreaCorrespondence: In-Hyuk HaJaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896, Republic of KoreaTel +82-2-2222-2740Fax +82-2-527-1869Email hanihata@gmail.comPurpose: Lycopus lucidus Turcz (LLT) is a potent traditional medicinal herb that exerts therapeutic effects, regulating inflammatory disorders. However, the precise mechanisms by which LLT plays a potent role as an anti-inflammatory agent are still unknown, and in particular, the effects of LLT on cortical neurons and related mechanisms of neuroinflammation have not been studied. The NLRP3 inflammasome pathway is one of the most well known as an important driver of inflammation. We therefore hypothesized that LLT, as an effective anti-inflammatory agent, might have neurotherapeutic potential by inhibiting the NLRP3 inflammasome pathway in cortical neurons.Materials and Methods: Primary cortical neurons were isolated from the embryonic rat cerebral cortex, and H2O2 was used to stimulate neuron damage in vitro. After treatment with LLT at three concentrations (10, 25, and 50 μg/mL), the expression of iNOS, NLRP3, ASC, caspase-1, IL-1β, IL-18, IL-6, and IL-10 was determined by immunocytochemistry, qPCR, and ELISA. Neuron apoptosis was also evaluated using Annexin V-FITC/PI double staining FACS analysis. Neural regeneration-related factors (BDNF, NGF, synaptophysin, NT3, AKT, and mTOR) were analyzed by immunocytochemistry and qPCR.Results: LLT effectively protected cultured rat cortical neurons from H2O2-induced neuronal injury by significantly inhibiting NLRP3 inflammasome activation. In addition, it significantly reduced caspase-1 activation, which is induced by inflammasome formation and regulated the secretion of IL-1β/IL-18. We demonstrated that LLT enhances axonal elongation and synaptic connectivity upon H2O2-induced neuronal injury in rat primary cortical neurons.Conclusion: It was first demonstrated in vitro that LLT suppresses NLRP3 inflammasome activation, attenuates inflammation and apoptosis, and consequently promotes neuroprotection and the stimulation of neuron repair, suggesting that it is a promising therapeutic for neurological diseases.Keywords: Lycopus lucidus Turcz, cortical neuron, hydrogen peroxide, NLRP3 inflammasome, neuroinflammation

Jin-Sun Park,1,* Joon-Han Shin,1,* Taek-Jong Hong,2 Hong-Seog Seo,3 Wan-Joo Shim,4 Sang-Hong Baek,5 Jin-Ok Jeong,6 Youngkeun Ahn,7 Woong-Chol Kang,8 Young-Hak Kim,9 Sang-Hyun Kim,10 Min-Su Hyon,11 Dong-Hoon Choi,12 Chang-Wook Nam,13 Tae-Ho Park,14 Sang-Chol Lee,15 Hyo-Soo Kim16 1Department of Cardiology, Ajou University School of Medicine, Suwon, 2Division of Cardiology, Pusan National University Hospital, Busan, 3Division of Cardiology, Korea University Guro Hospital, Korea University College of Medicine, 4Division of Cardiology, Korea University Anam Hospital, 5Cardiovascular Division, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 6Division of Cardiology, Chungnam National University Hospital, Daejeon, 7Division of Cardiology, Chonnam National University Hospital, Gwangju, 8Division of Cardiology, Gachon University Gil Hospital, Incheon, 9Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, 10Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 11Division of Cardiology, Soonchunhyang University Hospital, 12Division of Cardiology, Yonsei University Severance Hospital, Seoul, 13Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 14Division of Cardiology, Dong-A University Hospital, Busan, 15Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 16Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea *These authors contributed equally to this work Abstract: The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (–52.3% [2.8%] vs –0.6% [3.5%], P

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13 Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP

We report S 121,123 b nuclear quadrupole resonance (NQR) studies on single crystals of the narrow-gap semiconductor Ce3 Au3 Sb 4. Five NQR lines from the two Sb isotopes were successfully identified. The temperature dependence of the nuclear quadrupole frequency (νQ), as well as the static magnetic susceptibility (χ), is well explained by crystal-electric-field effects. The nuclear spin-lattice relaxation rates (T1-1) of both 121Sb and 123Sb increase rapidly with decreasing temperature. The ratio of T1-1 for the two Sb isotopes is constant at high temperature but it decreases at low temperatures, indicating the role of quadrupole fluctuations of the Ce ions. The possible origin of the large specific heat at low temperatures is discussed basing on our results. © 2010 The American Physical Society.

The chemical and biological characteristics of surface waters in Jinhae Bay were investigated over four seasons to understand water quality in light of the growing industrialisation occurring within this area. Jinhae Bay includes four smaller bays: Masan; Hangam; Jindong; and Gohyun. The water quality in Jinhae Bay varied spatially and seasonally. The water quality of both Hangam Bay and Masan Bay was highly degraded, demonstrating high concentrations of ammonia, nitrate, chlorophyllaand particulate organic carbon. Contamination from sewage was the dominant cause of the water quality deterioration in these bays. Conversely, the water quality in Jindong Bay and Gohyun Bay was not as severely affected as that of the above two bays. Water quality in Jinhae Bay was particularly poor in summer when nutrient loading was highest due to the run-off associated with high precipitation. Principal component analysis indicated that nitrogen contamination was a major factor influencing the water quality of Jinhae Bay. The effective reduction in high-nitrogen discharges is essential to improve water quality in Jinghae Bay. [ABSTRACT FROM PUBLISHER]

In this study, we investigated the relationship between seasonal/annual variation in water masses and nutrients, and the effects of nutrients on phytoplankton assemblages in the western Korea/Tsushima Strait. We collected water samples at least once per month from March 2006 to January 2008. There was seasonal variation in nutrient concentrations, with higher values in winter than in summer, and there was annual variation in chlorophyll-aconcentration and phytoplankton abundance during spring, with values being approximately three and 10 times higher, respectively, in 2007 than in 2006. Phytoplankton abundance was also approximately four times higher in 2007 than in 2006 during the stratification periods. Our findings suggest that when the supply of nutrients to the upper layer is increased as a result of the Tsushima Warm Water Current and the effect of typhoons, they regulate the abundance and composition of phytoplankton assemblages in the Korea/Tsushima Strait, inducing a succession from flagellates to diatoms. [ABSTRACT FROM PUBLISHER]

Background: Intra-articular distal radial fractures are frequently accompanied by a scapholunate interosseous ligament injury, which may adversely affect the outcomes. Arthroscopy may not be appropriate as a first-line evaluation method to diagnose these injuries because of time, expense, and availability issues. The purpose of this study was to evaluate the effectiveness of the modified carpal stretch test for screening for scapholunate interosseous ligament injuries in patients with an intra-articular distal radial fracture.Methods: The carpal stretch test is a radiographic evaluation in which disruption of the smooth arc of the proximal carpal row joint line indicates a lack of integrity of the scapholunate interosseous ligament. We modified the original carpal stretch test and prospectively performed the modified test on forty-eight patients with a total of forty-nine unstable intra-articular distal radial fractures. With the patient under anesthesia, the injured wrist was evaluated with the modified carpal stretch test with fluoroscopy. The wrist was then examined arthroscopically to classify the scapholunate interosseous ligament injury. Three observers independently determined whether there was disruption of the proximal carpal row joint line (Gilula's arc II), used as an indicator of a grade-III or IV scapholunate interosseous ligament tear, on fluoroscopic images. The fluoroscopic results were compared with the arthroscopic findings.Results: The average sensitivity of the modified carpal stretch test was 78%, the average specificity was 72%, the average positive predictive value was 60%, the average negative predictive value was 87%, and the average accuracy was 74%. The intraclass correlation coefficient (ICC) for interobserver agreement was 0.73, and the ICCs for intraobserver agreement were 0.86, 0.68, and 0.84 for the three observers.Conclusions: The modified carpal stretch test was useful to rule out grade-III or IV scapholunate interosseous ligament tears associated with intra-articular distal radial fractures, but it was not as useful to confirm the presence of a tear. This test may reduce the necessity for arthroscopic assessment to identify scapholunate interosseous ligament injuries following distal radial fractures and may improve the rates of detection of important carpal ligament injuries accompanying intra-articular distal radial fractures. [ABSTRACT FROM AUTHOR]

Secretory phospholipase A(2) (sPLA(2)) is involved in various cellular physiological and pathological responses, especially in inflammatory responses. Accumulating evidence suggests that inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. However, the involvement of sPLA(2) in cellular senescence is not clear. In this study, we found that sPLA(2) treatment induces cellular senescence in human dermal fibroblasts (HDFs), as confirmed by increases in senescence-associated beta-galactosidase activity, changes in cell morphology, and upregulation of p53/p21 protein levels. sPLA(2)-induced senescence was observed in p16-knockdown HDFs and p16-null mouse fibroblasts, but not in p53-knockdown HDFs and p53-null mouse fibroblasts. Treatment with sPLA(2) increases reactive oxygen species (ROS) production, and an antioxidant, N-acetylcysteine, inhibits sPLA(2)-induced cellular senescence. These results suggest that sPLA(2) has a role in cellular senescence in HDFs during inflammatory response by promoting ROS-dependent p53 activation and might therefore contribute to inflammatory disorders associated with aging. [ABSTRACT FROM AUTHOR]

Keywords:antiphospholipid syndrome; papillary muscle rupture; systemic lupus erythematosus [ABSTRACT FROM PUBLISHER]

Introduction: The objective of this study was to evaluate the short-term effects of clodronate, a first-generation bisphosphonate, on early alveolar bone remodeling and root resorption related to orthodontic tooth movement. Methods: The samples consisted of 54 sex-matched Wistar rats (weight, 180-230 g) allocated to the 2.5 mmol/L clodronate, 10 mmol/L clodronate, and control groups (n = 18 for each group). After application of a nickel-titanium closed-coil spring (force, 60 g) between the maxillary central incisor and first molar, 2.5 mmol/L of clodronate, 10 mmol/L of clodronate, or saline solution was injected into the subperiosteum adjacent to the maxillary first molar every third day. All animals received tetracycline, calcein, and alizarin red by intraperitoneal injection at 1, 6, and 14 days, respectively. The amounts of tooth movement were measured at 3, 6, 9, 12, and 15 days. The animals were killed at 4, 7, and 17 days. Histomorphometric analyses of bone mineral appositional rate, labeled surface, percentage of root resorption area, and number of root resorption lacunae of the mesiobuccal root of the maxillary first molar at 4, 7, and 17 days were done. One-way analysis of variance (ANOVA) with the post-hoc test were done for statistical analyses. Results: Rats in the 10 mmol/L clodronate group had significant decreases of tooth movement (12 and 15 days, P <0.05) and percentages of root resorption area and numbers of root resorption lacunae (7 day, P <0.05), and increases of labeled surface and mineral appositional rates (17 day, P <0.05) over those of the 2.5 mmol/L clodronate and control groups. Conclusions: Although clodronate might decrease root resorption related to orthodontic tooth movement, patients should be informed about a possible decrease in the amount of tooth movement and a prolonged period of orthodontic treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: The purpose of this study was to compare the efficacy and tolerability of amlodipine orotate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS:: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg amlodipine orotate or 5 mg amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either amlodipine orotate or amlodipine besylate) 4 weeks after enrollment if SiDBP was >/=90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement <90 mm Hg at the last clinical follow-up visit or an absolute reduction of >/=10 mm Hg in SiDBP from baseline until the last clinical follow-up visit. In addition, noninferiority of the difference in mean trough sitting systolic blood pressure (SiSBP) changes from baseline was analyzed for amlodipine orotate as compared with amlodipine besylate. The drug compliance rate was estimated by pillcount. RESULTS:: Eligible patients (n = 109; 43 women and 66 men) were randomly assigned to receive amlodipine orotate (n = 53) or amlodipine besylate (n = 56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P = NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the amlodipine orotate group and 50.0% [28/56] in the amlodipine besylate group; P = NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90-109 mm Hg] in the amlodipine orotate group and 100 [6] mm Hg [range, 90-108 mm Hg] in the amlodipine besylate group; P = NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125-179 mm Hg] in the amlodipine orotate group and 146 [10] mm Hg [range, 123-167 mm Hg] in the amlodipine besylate group; p = NS). The mean (SD) changes in SiDBP were -15.6 (6.3) mm Hg for the amlodipine orotate group and -14.5 (5.5) mm Hg for the amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, -0.87 to infinity), and because the lower boundary of the 95% CI was greater than -5 mm Hg, amlodipine orotate was considered noninferior to amlodipine besylate. The response rate was 48 of 51 (94.1%) in the amlodipine orotate group compared with 50 (92.6%) of 54 in the amlodipine besylate group after 8 weeks of treatment (P = NS). The mean (SD) compliance rates were 97.6% (3.6%) in the amlodipine orotate group and 96.5% (4.3%) in the amlodipine besylate group (P = NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the amlodipine orotate group vs 4/55 [7.3%] in the amlodipine besylate group; P = NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the amlodipine besylate group. No severe AEs were found in either group. CONCLUSION:: The reduction in SiDBP after 8 weeks of amlodipine orotate treatment was noninferior to that of amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of amlodipine orotate treatment were not significantly different from those of amlodipine besylate treatment. Both agents were wel tolerated. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a BA synthesis enzyme. In these Cyp8b1 -/- , and in wild-type mice administered CDCA, stroke infarct area was reduced. Elevated glutamate-induced excitotoxicity mediated by aberrant N-methyl-D-aspartate receptor (NMDAR) over-activation contributes to neuronal death in ischemic stroke. We found reduced glutamate-induced excitotoxicity in neurons from Cyp8b1 -/- and CDCA-treated wild-type mice. CDCA decreased NMDAR-mediated excitatory post-synaptic currents by reducing over-activation of NMDAR subunit GluN2B in wild-type brains. Synaptic NMDAR activity was also decreased in Cyp8b1 -/- brains. Expression and synaptic distribution of GluN2B were unaltered in Cyp8b1 -/- mice, suggesting CDCA may directly antagonize GluN2B-containing NMDARs. Supporting our findings, in a case-control cohort of acute ischemic stroke patients, we found lower circulatory CDCA. Together, our data suggest that CDCA, acting in the liver-brain axis, decreases GluN2B-containing NMDAR over-activation, contributing to neuroprotection in stroke., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Risk factors for local recurrence in patients with metastatic spinal cord compression (MSCC) has not been clearly investigated. So, the purpose of this study was to identify risk factors causing local recurrence following surgeries in patients with MSCC., Methods: We conducted a retrospective comparative study on 304 patients who underwent surgery for MSCC between March 2014 and February 2020. Local recurrence rate (LRR) was analyzed according to demographic variables, radiological variables such as level of spinal metastasis, number of non-spinal bone metastases, degree of spinal cord compression, spinal instability, and pathological fracture, and treatment-related variables such as origin of tumor, surgical treatment methods, and pre- and post- operative radiation therapy. Univariate and multivariate logistic regression analyses were performed to reveal the risk factors for local recurrence., Results: Among 304 patients with MSCC, 50 patients (16.4%) experienced local recurrence after surgery. Of the surgical methods, decompression alone (26/50, 52.0%) showed higher LRR compared to decompression with fixation (9/177, 5.1%) or corpectomy (11/89, 12.4%), (P = 0.002 and P = 0.018, respectively). Patients with renal cell carcinoma revealed higher LRR compared to other types (P = 0.014). It was found that the 3 or more level of spinal metastasis (P = 0.001), the 3 or more of extraspinal bone metastases (P = 0.028), and pathologic fracture (P = 0.003) were related with higher LRR. Smoking is also an independent risk factor for local recurrence in patients who underwent fixation (P = 0.026)., Conclusions: Symptomatic local recurrence may be influenced by several factors, including the extent of spinal and extraspinal bone metastasis, pathologic fractures, surgical approach, and tumor origin (RCC). These factors should be carefully considered by surgeons when evaluating the risk of symptomatic local recurrence after surgery., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by our facility’s Institutional Review Board of our institution (IRB number: 2022 − 0684). Informed consent was waived due to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Sphingosine-1-phosphate (S1P) is a multifunctional sphingolipid that has been implicated in regulating cellular activities in mammalian cells. Due to its therapeutic potential, there is a growing interest in developing efficient methods for S1P production. To date, the production of S1P has been achieved through chemical synthesis or blood extraction, but these processes have limitations such as complexity and cost. In this study, we generated an S1P-producing Saccharomyces cerevisiae strain by using metabolic engineering and introducing a heterologous sphingolipid biosynthetic pathway to demonstrate the possibility of microbial S1P production., Results: To construct the sphingosine-producing S. cerevisiae strain, both the sphingolipid delta 4 desaturase gene (DES1) and the alkaline ceramidase gene (ACER1) derived from Homo sapiens were introduced into the genome of S. cerevisiae by deleting the dihydrosphingosine phosphate lyase gene (DPL1) and the sphingoid long-chain base kinase gene (LCB5) to prevent S1P degradation and byproduct formation, respectively. The sphingosine-producing strain, DDLA, produced sphingolipids containing sphingosine. In flask fed-batch fermentation, the DDLA strain showed a higher production level of sphingosine under aerobic conditions with high initial cell density. The S1P-producing strain was generated by expressing the human sphingosine kinase gene (SPHK1) under the control of the inducible promoter, while deleting the ORM1 gene involved in the regulation of sphingolipid biosynthesis. The S1P-producing strain, DDLAOgS, exhibited the highest sphingosine production level under fed-batch fermentation in a bioreactor, achieving a 2.6-fold increase compared to flask fermentation. S1P biosynthesis in the DDLAOgS strain was verified by qualitative analysis using electrospray ionization mass spectrometry (ESI-MS)., Conclusions: We successfully developed a metabolically engineered S. cerevisiae as a platform strain for microbial production of S1P by introducing an exogenous pathway of sphingolipids metabolism. The engineered yeast strains showed significant capabilities for sphingolipid production, including S1P. To our knowledge, this is the first report demonstrating that engineered S. cerevisiae can be a major platform strain for producing microbial S1P., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Cross-coupling among the fundamental degrees of freedom in solids has been a long-standing problem in condensed matter physics. Despite its progress using predominantly three-dimensional materials, how the same physics plays out for two-dimensional materials is unknown. Here, we show that using 31 P nuclear magnetic resonance (NMR), the van der Waals antiferromagnet NiPS 3 undergoes a first-order magnetic phase transition due to the strong charge-spin coupling in a honeycomb lattice. Our 31 P NMR spectrum near the Néel ordering temperatureTN=155 K exhibits the coexistence of paramagnetic and antiferromagnetic phases within a finite temperature range. Furthermore, we observed a discontinuity in the order parameter atTNand the complete absence of critical behavior of spin fluctuations aboveTN, decisively establishing the first-order nature of the magnetic transition. We propose that a charge stripe instability arising from a Zhang-Rice triplet ground state triggers the first-order magnetic transition., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies., Methods: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD., Results: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001)., Conclusion: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR., Competing Interests: Declaration of competing interest Min J-H lectured, consulted, and received Honoria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Sanofi Genzyme, Teva-Handok, UCB, Samsung Bioepis and Mitsubishi Tanabe Pharma, Roche and Janssen, and received a National Research Foundation of Korea grant and an SMC Research and Development Grant., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although lymph node structures may be compromised in severe SARS-CoV-2 infection, the extent and parameters of recovery in convalescing patients remain unclear. Therefore, this study aimed to elucidate the nuances of lymphoid structural recovery and their implications for immunological memory in non-human primates infected with SARS-CoV-2. To do so, we utilized imaging-based spatial transcriptomics to delineate immune cell composition and tissue architecture formation in the lung draining lymph nodes during primary infection, convalescence, and reinfection from COVID-19. We noted the establishment of a germinal center with memory B cell differentiation within lymphoid follicles during convalescence accompanied by contrasting transcriptome patterns indicative of the acquisition of follicular helper T cells versus the loss of regulatory T cells. Additionally, repopulation of germinal center-like B cells was observed in the medullary niche with accumulating plasma cells along with enhanced transcriptional expression of B cell activating factor receptor over the course of reinfection. The spatial transcriptome atlas produced herein enhances our understanding of germinal center formation with immune cell dynamics during COVID-19 convalescence and lymphoid structural recovery with transcriptome dynamics following reinfection. These findings have the potential to inform the optimization of vaccine strategies and the development of precise therapeutic interventions in the spatial context., (Copyright © 2024. Published by Elsevier Inc.)

Background: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay., Methods: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX ® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed., Results: Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups., Conclusion: Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study., (© 2024. The Author(s).)

Thromboembolism, a serious complication in patients with liver abscesses, can lead to organ deterioration if left untreated. However, factors associated with thromboembolism in these patients remain poorly understood. We aimed to identify the factors associated with liver abscess complications, with a focus on thromboembolism and metastatic infection. Data from 325 patients diagnosed with liver abscesses between March 2019 and June 2023 were retrospectively collected. Baseline clinical and laboratory variables associated with thromboembolic events and metastatic infections were analyzed using logistic regression. A nomogram for predicting thromboembolism was constructed using significant predictors. Among the 325 patients, the median age was 68.0 years, and included 129 women. Fifty patients experienced thromboembolic events and 44 had metastatic infections. Significant predictors for thromboembolic events included white blood cell (WBC)  ≥ 20,000/µL (odds ratio [OR] 3.401, p = 0.002), platelet count < 100,000/µL (OR 3.291, p = 0.004), and abscess septation (OR 2.704, p = 0.007). Age ≥ 65 years (OR 0.457, p = 0.040), WBC  ≥ 20,000/µL (OR 3.340, p = 0.005), and abscess septation (OR 2.909, p = 0.008) were identified as factors associated with metastatic infections. A nomogram was constructed to predict thromboembolism using the following four variables: WBC  ≥ 20,000/µL platelet count < 100,000/µL, albumin < 2.8 g/dL, and abscess septation, and demonstrated an AUROC of 0.755. Our study is the first to develop a reliable nomogram for thromboembolism prediction, utilizing easily accessible clinical parameters. This innovative model enables clinicians to efficiently identify high-risk patients, facilitating the implementation of additional studies to mitigate the risk of overlooked thromboembolic events in these at-risk individuals., (© 2024. The Author(s).)

Understanding microscopic mechanisms of polarization retention characteristics in ferroelectric thin films is of great significance for exploring unusual physical phenomena inaccessible in the bulk counterparts and for realizing thin-film-based functional electronic devices. Perovskite (K,Na)NbO 3 is an excellent class of lead-free ferroelectric oxides attracting tremendous interest thanks to its potential applications to nonvolatile memory and eco-friendly energy harvester/storage. Nonetheless, in-depth investigation of ferroelectric properties of (K,Na)NbO 3 films and the following developments of nano-devices are limited due to challenging thin-film fabrication associated with nonstoichiometry by volatile K and Na atoms. Herein, ferroelectric (K,Na)NbO 3 films of which the atomic-level geometrical structures strongly depend on thickness-dependent strain relaxation are epitaxially grown. Nanopillar crystal structures are identified in fully relaxed (K,Na)NbO 3 films to the bulk states representing a continuous reduction of switchable polarization under air environments, that is, polarization retention failures. Protonation by water dissociation is responsible for the humidity-induced retention loss in nano-columnar (K,Na)NbO 3 films. The protonation-driven polarization retention failure originates from domain wall pinning by the accumulation of mobile hydrogen ions at charged domain walls for effective screening of polarization-bound charges. Conceptually, the results will be utilized for rational design to advanced energy materials such as photo-catalysts enabling ferroelectric tuning of water splitting., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: The aim of this study was to analyze the origins of prostatic arteries (PAs) in the Korean population and compare them with those reported in the literature., Materials and Methods: From April 2018 to February 2024, 108 male (mean age ± standard deviation: 71.6 ± 9.7 years) with lower urinary tract symptoms (n = 102) or refractory hematuria (n = 6) underwent prostatic artery embolization (PAE). Computed tomography and angiography images were retrospectively reviewed. The branching pattern of the internal iliac artery (IIA) was classified according to the Yamaki system. The origin of the PA was categorized using the de Assis definition, and the incidence of each type was recorded. A systematic literature review was conducted and the most common types of PA were investigated., Results: PAE was successfully implemented on 211 of the 216 pelvic sidewalls. PA cannulation failed in five sidewalls due to a steno-occlusive state. The most common IIA type was type A, in which the IIA was divided into the superior gluteal artery and gluteal-pudendal trunk (77%). Of 226 PAs analyzed, including 15 in 211 sidewalls exhibiting dual PAs, the most common PA origin was the internal pudendal artery (type IV, 35%), followed by the superior vesical (type I, 25%) and obturator (type III, 21%) arteries. Anterior division of IIA (type II) was less common (10%). Type V (uncommon origins) occurred in 8% of cases, including five distal internal pudendal arteries, four quadfurcations, three inferior gluteal arteries, three trifurcations, two medial femoral circumflex arteries, and two rectal arteries. Two of the five patients with surgically or endovascularly altered anatomy were successfully treated via PAs originating from the medial femoral circumflex arteries. Globally, type I is the most common PA type., Conclusion: In the Korean population, the most common IIA pattern and PA origin were types A and IV, respectively., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

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.)