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Purpose: Bypass surgery is regarded as the standard treatment option for symptomatic and hemodynamically unstable moyamoya disease (MMD). However, there is ongoing debate about the most effective type of bypass surgery. We aimed to analyze the long-term outcomes of combined and indirect bypasses for MMD patients through intra-individual comparisons., Methods: Of the 896 patients who underwent 1084 bypass surgeries between 2007 and 2021, 24 patients with MMD who underwent combined bypass on one side and indirect bypass on the other side were ultimately enrolled in this study. Clinical, angiographic and hemodynamic outcomes were retrospectively evaluated., Results: Three asymptomatic strokes (12.5%) occurred within 30 postoperative days in each group. Postoperative strokes after 30 days occurred in 3 patients (12.5%) with 3 hemorrhagic events and 1 cerebral infarction, only in indirect bypass, while no stroke occurred in hemispheres treated with combined bypass. The revascularization area relative to supratentorial area was significantly greater in combined bypass than in indirect bypass, both in short-term and long-term periods (64.9% versus 43.9% in short-term and 75.7% versus 54.9% in long-term; P < .001, respectively). Hemodynamic outcomes showed significantly greater increases in acetazolamide-challenged cerebral blood flow (CBF acz ) during short-term follow-up (P = .04) and in both basal CBF (CBF bas ) and CBF acz during long-term follow-up (P = .014 and P = .009, respectively) in combined bypass than in indirect bypass., Conclusion: Combined bypass may be a more effective treatment option for MMD based on its higher revascularization area and favorable hemodynamic results compared to indirect bypass in the same patient., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In this paper, a concept of integrated CO 2 capture and reverse water-gas shift (ICCrWGS) process was proposed using NH 3 as the H 2 carrier. The CO 2 efficiency and total thermal energy consumption for the conventional rWGS, ICCrWGS using H 2 (H 2 -ICCrWGS) and NH 3 (NH 3 -ICCrWGS), were calculated. ICCrWGS using H 2 and NH 3 was conducted over the thermally stable Ni/CaZr dual-function materials (DFMs). NH 3 decomposition, CO 2 capture capacity, CO 2 conversion, and CO selectivity were addressed at different reaction temperatures, and the optimal temperature was determined to be 650 °C. The Ni/CaZr DFMs exhibited stable CO 2 capture capacity and CO productivity during ICCrWGS using the NH 3 carrier. A carbonate spillover mechanism for CO production over the Ni/CaZr DFMs in NH 3 -ICCrWGS was proposed using in situ diffuse reflectance infrared Fourier transform spectroscopy. It was found that CO is produced from the bridged bidentate carbonate route in the Ni-CaO interface.

For successful infection, the life-threatening pathogen Vibrio vulnificus elaborately regulates the expression of survival and virulence genes using various transcription factors (TFs). In this study, a library of the V. vulnificus mutants carrying specific signature tags in 285 TF genes was constructed and subjected to 16 phenotypic analyses. Consequently, 89 TFs affecting more than one phenotype of V. vulnificus were identified. Of these, 59 TFs affected the in vitro survival including growth, stress resistance, biofilm formation and motility, and 64 TFs affected the virulence of V. vulnificus. Particularly, 27 of the 64 TFs enhanced the in vitro hemolytic or cytotoxic activities, and 8 of the 27 TFs also increased the in vivo brine shrimp or murine infectivities of V. vulnificus. Among the eight TFs, HlyU, IscR, NagC, MetJ and Tet2 did not affect the growth of V. vulnificus but still regulated the expression of major exotoxin genes, including rtxA, vvhA and plpA, thereby emerging as potential drug targets for anti-virulence therapies with low selective pressure for developing resistance. Altogether, this study characterized the functions of TFs at a genome-wide scale and identified novel targets to control the virulence of V. vulnificus., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: The objective of this study was to compare clinical outcomes between in situ fixation and fixation after closed reduction (CR) in patients aged 50 and above with valgus impacted femoral neck fractures using data from multiple centers., Methods: Design: Retrospective multicenter cohort study., Setting: Five tertiary-care university hospitals., Patient Selection Criteria: Patients aged 50 and above, treated with operative fixation of valgus impacted femoral neck fractures using multiple cannulated screws from 2003 to 2019., Outcome Measures and Comparisons: Complications such as fixation failure, osteonecrosis of femoral head (ONFH), and reoperation were compared between the groups (in situ fixation group and fixation after CR group). Postoperative EuroQol-5 Dimension (EQ-5D), Harris Hip Score (HHS), and Koval's grade were compared., Results: The mean age of the 206 patients (161 in situ fixation group, 45 in fixation after CR group) who met the inclusion criteria was 68.9 ± 10.9 years (range, 50 to 95 years). There were 39 men and 167 women. Fixation failure occurred in 11.2% (6.8% of in situ fixation group vs 26.7% of fixation after CR group, p = 0.002). Reoperation was required for 10.2% (7.5% of in situ fixation group vs 20% of fixation after CR group, p = 0.023). Fixation failure and reoperation rates were significantly higher in the fixation after CR group than in the in-situ fixation group (odds ratio = 4.757, p = 0.002 and odds ratio = 3.104, p = 0.023, respectively). At the two-year follow-up, ONFH occurred in 5.8% (9 out of 161, in situ fixation group vs 3 out of 45, fixation after CR group). There was no significant difference in the occurrence of ONFH between the two groups (p = 0.727). The Koval's grade at 6 and 12 months demonstrated better results in the in-situ group (p = 0.027, 0.044, respectively). Postoperative EQ-5D and HHS scores showed no statistically significant differences between the two groups., Conclusion: In patients aged 50 years or older with valgus impacted femoral neck fractures, when fixation was done after reduction, the reoperation rate was higher due to fixation failure compared to in-situ fixation. There was no significant difference in the incidence of ONFH in valgus impacted femoral neck fractures regardless of whether reduction was performed., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/ IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigen-B27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Proline is a major substrate in collagen biosynthesis and is required for collagen molecule formations. However, detailed explanations of the molecular basis through which proline functions in collagen biosynthesis have yet to be provided. Thus, genome-wide screening was employed to elucidate these in the pre-osteoblastic MC3T3-E1 and human periodontal ligament fibroblast (hPDLF) cell lines. Indeed, both cell lines represent important sources for collagen biosynthesis and tissue regeneration in the dental region, specifically treating extracellular proline during cultivations. The altered gene expression patterns were identified, and the precise expression patterns were confirmed by microarray. Cell viability and osteogenic differentiation patterns were examined using a range of experimental methods, such as the MTS assay, ALP staining, ARS staining, and collagen (COL)-type1A ELISA. Overall, we revealed a cell line-specific function of exogenous proline in collagen biosynthesis during osteogenic differentiation conditions with the candidate signaling pathways. These putative signaling networks could represent plausible answers to understanding collagen biosynthesis for regenerating connective tissues such as skin, muscle, and bone., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Ethnopharmacological Relevance: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD)., Aim of the Study: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA)., Materials and Methods: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured., Results: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside., Conclusions: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD., 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.)

Objectives: The purposes of this study were to investigate the frequency of screwdriver stripping in the head of the locking screw that attaches to the side plate to the femur shaft among the patients who underwent implant removal after Femoral Neck System (FNS) for femoral neck fracture, to determine the risk factors for locking head screw stripping in FNS treatment of femoral neck fracture, and to suggest a surgical tip that removes FNS, which is difficult to remove due to screw stripping., Methods: Design: Retrospective cohort study., Setting: Eight Urban tertiary referral academic hospitals., Patient Selection Criteria: Included were patients with OTA/AO 31-B1, 31-B2, and 31-B3 femoral neck fractures who underwent surgical fixation with FNS from Nov 2019 to Feb 2023., Outcome Measures and Comparisons: The frequency of locking head screw stripping of FNS during the implant removal was evaluated., Results: Among the 47 patients (18 (38%) men and 29 (62%) women) who met the inclusion criteria with average age of 59.2 years (range, 28 to 94 years), 13 (27.7%) experienced screwdriver stripping in the head of the distal locking screw during FNS removal surgery. A higher BMI showed a borderline significant association with the stripping in the adjusted model (OR = 1.233; 95% CI: 0.988-1.539; p = 0.064). No other variables showed significant association with the stripped locking head screw (p>0.05)., Conclusions: Stripping of the screwdriver within the head of the distal locking screw occurred in over one quarter of cases. While a higher BMI demonstrated a borderline significant association, none of the other variables examined showed a statistically significant relationship with the stripped locking head screw., Levels of Evidence: Level III (retrospective cohort study)., Competing Interests: Conflict of interest: Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In drug discovery, human organ-on-a-chip (organ chip) technology has emerged as an essential tool for preclinical testing, offering a realistic representation of human physiology, real-time monitoring, and disease modeling. Polydimethylsiloxane (PDMS) is commonly used in organ chip fabrication owing to its biocompatibility, flexibility, transparency, and ability to replicate features down to the nanoscale. However, the porous nature of PDMS leads to unintended absorption of small molecules, critically affecting the drug response analysis. Addressing this challenge, the precision drug testing organ chip (PreD chip) is introduced, an innovative platform engineered to minimize small molecule absorption while facilitating cell culture. This chip features a PDMS microchannel wall coated with a perfluoropolyether-based lubricant, providing slipperiness and antifouling properties. It also incorporates an ECM-coated semi-porous membrane that supports robust multicellular cultures. The PreD chip demonstrates its outstanding antifouling properties and resistance to various biological fluids, small molecule drugs, and plasma proteins. In simulating the human gut barrier, the PreD chip demonstrates highly enhanced sensitivity in tests for dexamethasone toxicity and is highly effective in assessing drug transport across the human blood-brain barrier. These findings emphasize the potential of the PreD chip in advancing organ chip-based drug testing methodologies., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

This study investigates the impact of sodium channel protein type 1 subunit alpha (SCN1A) gene knockout (SCN1A KO) on brain development and function using cerebral organoids coupled with a multiomics approach. From comprehensive omics analyses, we found that SCN1A KO organoids exhibit decreased growth, dysregulated neurotransmitter levels, and altered lipidomic, proteomic, and transcriptomic profiles compared to controls under matrix-free differentiation conditions. Neurochemical analysis reveals reduced levels of key neurotransmitters, and lipidomic analysis highlights changes in ether phospholipids and sphingomyelin. Furthermore, quantitative profiling of the SCN1A KO organoid proteome shows perturbations in cholesterol metabolism and sodium ion transportation, potentially affecting synaptic transmission. These findings suggest dysregulation of cholesterol metabolism and sodium ion transport, with implications for synaptic transmission. Overall, these insights shed light on the molecular mechanisms underlying SCN1A-associated disorders, such as Dravet syndrome, and offer potential avenues for therapeutic intervention., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm 2 ) ECD., Methods: We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm 2 and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery., Results: Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57-76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07-89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01)., Conclusions: R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings., (© 2024. The Author(s).)

Background: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis., Results: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069)., Conclusion: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor., 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.)

Seamless integration and conformal contact of soft electronics with tissue surfaces have emerged as major challenges in realizing accurate monitoring of biological signals. However, the mechanical mismatch between the electronics and biological tissues impedes the conformal interfacing between them. Attempts have been made to utilize soft hydrogels as the bioelectronic materials to realize tissue-comfortable bioelectronics. However, hydrogels have several limitations in terms of their electrical and mechanical properties. In this study, we present the development of a 3D-printable modulus-tunable hydrogel with multiple functionalities. The hydrogel has a cross-linked double network, which greatly improves its mechanical properties. Functional fillers such as XLG or functionalized carbon nanotubes (fCNT) can be incorporated into the hydrogel to provide tunable mechanics (Young's modulus of 10-300 kPa) and electrical conductivity (electrical conductivity of ∼20 S/m). The developed hydrogel exhibits stretchability (∼1000% strain), self-healing ability (within 5 min), toughness (400-731 kJ/m 3 ) viscoelasticity, tissue conformability, and biocompatibility. Upon examining the rheological properties in the modulated region, hydrogels can be 3D printed to customize the shape and design of the bioelectronics. These hydrogels can be fabricated into ring-shaped strain sensors for wearable sensor applications., 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.)

Objective: To determine if insomnia-related factors differ depending on the presence of depression in patients with epilepsy., Methods: This cross-sectional multicenter study collected data on depressive symptoms, insomnia symptoms, and excessive daytime sleepiness, which were defined as a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10, an Insomnia Severity Index (ISI) score of ≥ 15, and an Epworth Sleepiness Scale (ESS) of ≥ 11, respectively. Further, uncontrolled seizures were defined as one or more seizures per month during antiseizure medications treatment. A stepwise logistic regression analysis was conducted, with a logistic regression with interaction terms performed to identify differences in insomnia-related factors depending on depressive symptoms., Results: Of 282 adults with epilepsy (men, 58 %; mean age, 40.4 ± 13.9 years), a PHQ-9 score ≥ 10, an ISI score ≥ 15, an ESS score ≥ 11 were noted in 23.4 % (n = 66), 20.2 % (n = 57), and 12.8 % (n = 36), respectively. More patients with depressive symptoms had an ISI score ≥ 15 (56.1 % vs. 9.3 %; p < 0.001) than those without. In multiple logistic regression, uncontrolled seizures (odds ratio [OR], 4.896; p < 0.01), daytime sleepiness (OR, 5.369; p < 0.05), and a history of psychiatric disorders (OR, 3.971; p < 0.05) were identified as significant factors that were more likely to be associated with an ISI score ≥ 15; however, this was only true in patients without depressive symptoms. In contrast, use of perampanel (OR, 0.282; p < 0.05) was less likely associated, while female sex (OR, 3.178; p < 0.05) was more likely associated with an ISI score ≥ 15 only in patients with depressive symptoms., Conclusions: Insomnia-related factors in patients with epilepsy may differ between patients with and without depression. Our findings of different insomnia-related factors based on the presence of depression may facilitate the management of patients with epilepsy., 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 Inc. All rights reserved.)

This study aimed to investigate the anti-allergic activity of compounds isolated from Geranium wilfordii Maxim. and to suggest potential therapeutic agents for allergies. Nine compounds were isolated from an ethanolic G. wilfordii extract using chromatographic methods and identified chemically and by spectroscopic analysis. These compounds were identified using reported literature data as brevifolin carboxylic acid ( 1 ), chlorogenic acid ( 2 ), corilagin ( 3 ), ellagic acid ( 4 ), geraniol ( 5 ), kaempferol 3- O -dirhamnoside ( 6 ), kaempferol 3- O -neohesperidoside ( 7 ), protocatechuic acid ( 8 ), and gallic acid ( 9 ). All nine identified compounds were assessed for including IL-4 mRNA expression and β-hexosaminidase release in RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA. IL-4 gene expression assay showed that corilagin ( 3 ) potently inhibited IL-4 production, and β-hexosaminidase release assay showed that protocatechuic acid ( 8 ) markedly reduced histamine release. The study shows that of the nine compounds isolated from G. wilfordii , corilagin ( 3 ), and protocatechuic acid ( 8 ) are potential treatments for allergy-related diseases.

Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group ( n = 40, 450 mg ThinkGIN™/day) or a placebo group ( n = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.

Background: Hemiarthroplasty is frequently used to treat displaced femoral neck fractures in elderly patients, but it has a higher risk of postoperative dislocation. We introduced the posterior approach and inferior capsulotomy (PAICO) to enhance joint stability after bipolar hemiarthroplasty for femoral neck fracture. We evaluated whether the PAICO would have a lower dislocation rate than the conventional posterior approach with superior capsulotomy., Methods: From January 2021 to December 2021, we prospectively recruited 25 patients (25 hips) aged 50 years or older who underwent bipolar hemiarthroplasty for femoral neck fractures due to low-energy trauma as the PAICO group. We compared the PAICO group with a historical control group who had undergone hemiarthroplasty in 7 institutes between 2010 and 2020. The primary endpoint was dislocation within 1 year after the surgery. We compared data from the PAICO group with the data from the historical control group from the Korean Hip Fracture Registry which was carried out in South Korea., Results: A total of 25 patients (25 hips) were enrolled in the present study; 3,477 patients (3,571 hips) who underwent bipolar hemiarthroplasty were reviewed as the historical control group. In the PAICO group, we observed no dislocation, whereas the dislocation rate in the control group was 1.3%., Conclusions: In patients with displaced femoral neck fractures, the PAICO approach demonstrated comparable results in operation time and complication rates when compared to bipolar hemiarthroplasty using superior capsulotomy. Notably, there were no observed cases of dislocation among patients who underwent the PAICO approach. We recommend this PAICO approach to surgeons using the posterior approach, hoping to prevent dislocation in bipolar hemiarthroplasty., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Long-term hepatic damage is associated with human morbidity and mortality owing to numerous pathogenic factors. A variety of studies have focused on improving liver health using natural products and herbal medicines. We aimed to investigate the effect of enzyme-treated Zizania latifolia ethanol extract (ETZL), which increases the content of tricin via enzymatic hydrolysis, for 8 weeks on liver-related outcomes, lipid metabolism, antioxidant activity, and fatigue compared to a placebo. Healthy Korean adult males aged 19-60 years were randomized into ETZL treatment and placebo groups, and alcohol consumption was 24.96 and 28.64 units/week, respectively. Alanine transaminase, a blood marker associated with liver cell injury, significantly decreased after 8 weeks compared to the baseline in the ETZL treatment group ( p = 0.004). After 8 weeks, the treatment group showed significant changes in the levels of high-density lipoprotein and hepatic steatosis index compared to the baseline ( p = 0.028 and p = 0.004, respectively). ETZL treatment tended to reduce antioxidant-activity-related factors, total antioxidant status, and malondialdehyde, but there was no significant difference. In the multidimensional fatigue scale, ETZL treatment showed a significant reduction in general fatigue and total-fatigue-related values after 8 weeks compared to the baseline ( p = 0.012 and p = 0.032, respectively). Taken together, the 8-week treatment of enzyme-treated Zizania latifolia ethanol extract demonstrated positive effects on liver-related outcomes, lipid metabolism, and mental fatigue without adverse effects on safety-related parameters.

Introduction: Prohibitin (PHB) is an essential scaffold protein that modulates signaling pathways controlling cell survival, metabolism, inflammation, and bone formation. However, its specific role in periodontium development remains less understood. This study aims to elucidate the expression pattern and function of PHB in periodontium development and its involvement in alveolar bone formation. Methods: Immunolocalization of PHB in the periodontium of postnatal (PN) mice were examined. Phb morpholino was micro-injected into the right-side mandible at PN5, corresponding to the position where the alveolar bone process forms in relation to the lower first molar. The micro-injection with a scramble control (PF-127) and the left-side mandibles were used as control groups. Five days post-micro-injection, immunohistochemical analysis and micro-CT evaluation were conducted to assess bone mass and morphological changes. Additionally, expression patterns of signaling molecules were examined following Phb downregulation using 24-h in vitro cultivation of developing dental mesenchyme at E14.5. Results: The immunostaining of PHB showed its localization in the periodontium at PN5, PN8, and PN10. The in vitro cultivation of dental mesenchyme resulted in alterations in Bmps, Runx2, and Wnt signalings after Phb knock-down. At 5 days post-micro-injection, Phb knocking down showed weak immunolocalizations of runt-related transcription factor (RUNX2) and osteocalcin (OCN). However, knocking down Phb led to histological alterations characterized by decreased bone mass and stronger localizations of Ki67 and PERIOSTIN in the periodontium compared 1 to control groups. The micro-CT evaluation showed decreased bone volume and increased PDL space in the Phb knock-down specimens, suggesting its regulatory role in bone formation. Discussion: The region-specific localization of PHB in the margin where alveolar bone forms suggests its involvement in alveolar bone formation and the differentiation of the periodontal ligament. Overall, our findings suggest that Phb plays a modulatory role in alveolar bone formation by harmoniously regulating bone-forming-related signaling molecules during periodontium development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aryal, Han, Rana, Neupane, Kim, Pokharel, Ha, Jung, An, Kim, Yamamoto, Lee, An, Suh, Kim and Sohn.)

Objective: To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA)., Methods: Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted., Results: In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men., Conclusions: RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction : Basicervical femoral neck fracture (FNF) is an uncommon type of femoral neck fracture and is associated with an increased risk of fixation failure due to its inherent instability. The purpose of this study was to compare the surgical parameters and reoperation rate between the use of a multiple cannulated screw (MCS) and fixed angle device (FAD) in treating basicervical FNFs. Methods : We retrospectively reviewed the records of 885 patients who underwent internal fixation between May 2004 and August 2019 to determine basicervical FNF with at least 12 months of follow-up. Among the identified 77 patients with basicervical FNF, 17 patients who underwent multiple cannulated screw (MCS) fixation and 36 patients who underwent fixed angle device (FAD) fixation were included. We compared the rates of fracture-site collapse and reoperations according to the fixation device. Results : Among the 53 patients with basicervical FNF, 13 patients (24.5%) sustained surgical complications (8 collapses of fracture site and 5 reoperations). The reoperation rate in the MCS group was significantly higher than that in the FAD group (23.5% vs. 2.8%, p = 0.016), without any significant difference in the collapse of the fracture site (11.8% vs. 16.7%, p = 0.642). Conclusions : Although basicervical FNF was rare among hip fractures, fracture site collapse was prevalent and prone to fixation failure. Surgeons should keep this in mind, and consider FAD for basicervical FNF.

Periodontitis is known to be affected by high-glucose conditions, which poses a challenge to periodontal tissue regeneration, particularly in bone formation. In this study, the potential effects of resveratrol (3,5,4'-trihydroxystilbene, RSV) in facilitating bone formation under high-glucose conditions after periodontitis has been investigated. We focused on the analysis of osteoblasts and periodontal ligament cells, which are essential for bone formation including cell proliferation and differentiation. And we aimed to investigate the impact of RSV on bone healing, employed diabetic mouse model induced by streptozotocin and confirmed through histological observation. High-glucose conditions adversely affected cell proliferation and ALP activity in both MC3T3-E1 and hPDLF in vitro , with more significant impact on MC3T3-E1 cells. RSV under high-glucose conditions had positive effects on both, showing early-stage effects for MC3T3-E1 cells and later-stage effects for hPDLF cells. RSV seemed to have a more pronounced rescuing role in MC3T3-E1 cells. Increased ALP activity was observed and the expression levels of significant genes, such as Col 1, TGF-β1, ALP, and OC, in osteogenic differentiation were exhibited stage-specific expression patterns. Upregulated Col 1 and TGF-β1 were detected in the early stage, and then ALP and OC expressions became more pronounced in the later stages. Similarly, stronger positive reactions against RUNX2 were detected in the RSV-treated group compared to the control. Furthermore, in in vivo experiment, RSV stimulates the growth and differentiation of osteoblasts, thereby promoting bone formation. High-glucose levels have the potential to impair cellular functions and the regenerative capacity to facilitate bone formation with MC3T3-E1 rather than hPDLF cells. Resveratrol appears to facilitate the inherent abilities of MC3T3-E1 cells compared with hPDLF cells, indicating its potential capacity to restore functionality during periodontal regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hwang, Kim, Kim, Kim, Park, Lee, Kim and Suh.)

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc&#95;1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc&#95;1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc&#95;1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc&#95;1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health., (© 2024. The Author(s).)

Purpose: Studies on attention-deficit hyperactivity disorder (ADHD) are scarce in adults with epilepsy. This study aimed to investigate the risk factors for ADHD and determine whether ADHD is directly associated with the risk of suicide in adults with epilepsy., Methods: ADHD was assessed using the Structured Clinical Interview for the DSM-5 Disorders Clinical Version. The Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0, Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and Generalized Anxiety Disorder-7 (GAD-7) were also used. Suicide risk was defined as a MINI suicidality score of ≥ 1. Stepwise logistic regression and mediation analyses were conducted., Results: Of the 157 adults with epilepsy, 19 (12.1 %) were diagnosed with ADHD, including inattentive (5.7 %), hyperactive (3.8 %), and combined (2.5 %) types. Thirty-two subjects (20.4 %) had a risk of suicide. ADHD was insignificantly associated with any epilepsy-related factors. The diagnosis of ADHD was not associated with suicide risk independent of NDDIE ≥ 14 and GAD-7 ≥ 7. Mediation effects of ADHD on suicidality using NDDIE ≥ 14 (odds ratio [OR] 2.850, 95 % confidence interval [CI] 1.398-5.811, p = 0.004) or GAD-7 ≥ 7 (OR 3.240, 95 % CI 1.537-6.828, p = 0.002) were statistically significant, with the proportion mediated being 84.5 % or 92.0 % of the total ADHD effect, respectively. These models were adjusted for age, sex, and composite epilepsy severity scores., Conclusions: ADHD was diagnosed in 12.1% of adults with epilepsy and was not associated with any epilepsy-related factors. ADHD was indirectly associated with the risk of suicide resulting from depression and anxiety in adults with epilepsy., 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 Inc. All rights reserved.)

Nymphoides peltata has been used as a medicinal herb in traditional medicines to treat strangury, polyuria, and swelling. The phytochemical investigation of the MeOH extract of N. peltata roots led to the isolation of three iridoid glycosides and three coumarin glycoside derivatives, which were characterized as menthiafolin ( 1 ), threoninosecologanin ( 2 ), callicoside C ( 3 ), and scopolin ( 4 ), as well as two undescribed peltatamarins A ( 5 ) and B ( 6 ). The chemical structures of the undescribed compounds were determined by analyzing their 1 dimensional (D) and 2D nuclear magnetic resonance (NMR) spectra and using high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS), along with the chemical reaction of acid hydrolysis. The wound healing activities of the isolated compounds 1 - 6 were evaluated using a HaCaT cell scratch test. Among the isolates, scopolin ( 4 ) and peltatamarin A ( 5 ) promoted HaCaT cell migration over scratch wounds, and compound 5 was the most effective. Furthermore, compound 5 significantly promoted cell migration without adversely affecting cell proliferation, even when treated at a high dose (100 μM). Our results demonstrate that peltatamarin A ( 5 ), isolated from N. peltata roots, has the potential for wound healing effects.

Black ginseng (BG) is processed ginseng traditionally made in Korea via the steaming and drying of ginseng root through three or more cycles, leading to changes in its appearance due to the Maillard reaction on its surface, resulting in a dark coloration. In this study, we explored markers for differentiating processed ginseng by analyzing the chemical characteristics of BG. We elucidated a new method for the structural identification of ginsenoside metabolites and described the features of processed ginseng using UPLC-QTOF-MS in the positive ion mode. We confirmed that maltose, glucose, and fructose, along with L-arginine, L-histidine, and L-lysine, were the key compounds responsible for the changes in the external quality of BG. These compounds can serve as important metabolic markers for distinguishing BG from conventionally processed ginseng. The major characteristics of white ginseng, red ginseng, and BG can be distinguished based on their high-polarity and low-polarity ginsenosides, and a precise method for the structural elucidation of ginsenosides in the positive ion mode is presented.

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance ( 1 H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1 H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.

Despite the extensive global consumption of architectural paint, the toxicological effects of aged exterior paint particles on terrestrial biota remain largely uncharacterized. Herein, we assessed the toxic effect of aged paint particles on soil environments using the nematode Caenorhabditis elegans ( C. elegans ) as a test organism. Various types of paint particles were generated by fragmentation and sequential sieving (500-1000, 250-500, 100-250, 50-100, 20-50 μm) of paint coatings collected from two old residential areas. The paint particles exerted different levels of toxicity, as indicated by a reduction in the number of C. elegans offspring, depending on their size, color, and layer structure. These physical characteristics were found to be closely associated with the chemical heterogeneity of additives present in the paint particles. Since the paint particle sizes were larger than what C. elegans typically consume, we attributed the toxicity to leachable additives present in the paint particles. To assess the toxicity of these leachable additives, we performed sequential washings of the paint particles with distilled water and ethanol. Ethanol washing of the paint particles significantly reduced the soil toxicity of the hydrophobic additives, indicating their potential environmental risk. Liquid chromatography-mass spectrometry analysis of the ethanol leachate revealed the presence of alkyl amines, which exhibited a high correlation with the toxicity of the paint particles. Further toxicity testing using an alkyl amine standard demonstrated that a paint particle concentration of 1.2% in soil could significantly reduce the number of C. elegans offspring. Our findings provide insights into the potential hazards posed by aged paint particles and their leachable additives in the terrestrial environment.

Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk -deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced β-catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk -deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca 2+ -NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 ( Opg/Rankl ) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk -deficient mice compared with wild-type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis., Competing Interests: All the authors state that they have no conflicts of interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

New approaches for elucidating mechanisms of diseases including environmental diseases, cancer, metabolic diseases, infectious diseases are challenging. After the presentation on elucidating the mechanism of cancer and infectious diseases, lectures by Dr. Tae-Young Kim (Korea) on metabolic deuterium oxide labeling in environmental diseases, Dr. Rosalia Rodriguez-Rodriguez (Spain) on targeting the hypothalamus with nanomedicines to treat metabolic diseases, Dr. Chang-Beom Park (Korea) on methodological approach for evaluation of the environmental diseases were presented. The deeper understanding of the global research approaches on diseases will be expected based on the fruitful discussion at the international symposium.

Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca 2+ ] i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and anti-arthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors., (© 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of Bifidobacterium longum NBM7-1 (CKD1) with anti-diabetic medicines, Lobeglitazone Ⓡ (LO), Sitagliptin Ⓡ (SI), and Metformin Ⓡ (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic β-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, β-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with Metformin Ⓡ . This combination induced an increase in the abundance of Rikenellaceae and Alistipes related negatively to the T2DM incidence while reducing the causative species of Cryptosporangium, Staphylococcaceae , and Muribaculaceae . These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of B. longum NBM7-1(CKD1) reduced the medicines' dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota.

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG-35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type-specific responses, with AMG-35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG-35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF-β1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG-35 elicits osteoblast differentiation through TGF-β1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-β1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG-35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment., (© 2023 Wiley Periodicals LLC.)

Nymphoides peltata (Menyanthaceae) has been used as a medicinal herb in traditional medicines to treat conditions such as strangury, polyuria, swelling, and as a diuretic and antipyretic. In our ongoing research to discover novel structural and/or biological natural products in natural resources, five flavonoids, quercetin ( 1 ), quercitrin ( 2 ), isoquercetin ( 3 ), quercetin-3- O -vicianoside ( 4 ), and rutin ( 5 ), as well as a new flavonoid glycoside, 3‴- O -foliamenthoyl-rutin ( 6 ), were isolated from the MeOH extract of N. peltata roots. The chemical structure of the new compound ( 6 ) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR) electrospray ionization mass spectroscopy (ESIMS), along with a chemical reaction. The wound-healing activities of the isolated compounds ( 1 - 6 ) were evaluated using a HaCaT cell scratch test. Among the isolates, isoquercetin ( 3 ), quercetin-3- O -vicianoside ( 4 ), and 3‴- O -foliamenthoyl-rutin ( 6 ) promoted HaCaT cell migration over scratch wounds, with compound 4 being the most effective. Our findings provide experimental data supporting the potential of quercetin-3- O -vicianoside ( 4 ) as a wound-healing agent.

Competing Interests: The authors report no conflicts of interest.

Background: The modulation of immune responses by probiotics is crucial for local and systemic immunity. Recent studies have suggested a correlation between gut microbiota and lung immunity, known as the gut-lung axis. However, the evidence and mechanisms underlying this axis remain elusive., Results: In this study, we screened various Lactobacillus (L.) strains for their ability to augment type I interferon (IFN-I) signaling using an IFN-α/β reporter cell line. We identified L. paracasei (MI29) from the feces of healthy volunteers, which showed enhanced IFN-I signaling in vitro. Oral administration of the MI29 strain to wild-type B6 mice for 2 weeks resulted in increased expression of IFN-stimulated genes and pro-inflammatory cytokines in the lungs. We found that MI29-treated mice had significantly increased numbers of CD11c + PDCA-1 + plasmacytoid dendritic cells and Ly6C hi monocytes in the lungs compared with control groups. Pre-treatment with MI29 for 2 weeks resulted in less weight loss and lower viral loads in the lung after a sub-lethal dose of influenza virus infection. Interestingly, IFNAR1 -/- mice did not show enhanced viral resistance in response to oral MI29 administration. Furthermore, metabolic profiles of MI29-treated mice revealed changes in fatty acid metabolism, with MI29-derived fatty acids contributing to host defense in a Gpr40/120-dependent manner., Conclusions: These findings suggest that the newly isolated MI29 strain can activate host defense immunity and prevent infections caused by the influenza virus through the gut-lung axis. Video Abstract., (© 2023. The Author(s).)

With rapid industrialization, urbanization, and climate change, the impact of environmental factors on human health is becoming increasingly evident and understanding the complex mechanisms involved is vital from a healthcare perspective. Nevertheless, the relationship between physiological stress resulting from environmental stressors and environmental disease is complex and not well understood. Chronic exposure to environmental stressors, such as air and water contaminants, pesticides, and toxic metals, has been recognized as a potent elicitor of physiological responses ranging from systemic inflammation to immune system dysregulation causing or progressing environmental diseases. Conversely, physiological stress can exacerbate susceptibility to environmental diseases. Stress-induced alterations in immune function and hormonal balance may impair the ability to detoxify harmful substances and combat pathogens. Additionally, prolonged stress can impact lifestyle choices, leading to harmful behaviors. Understanding the link between physiological stress and environmental disease requires a systematic, multidisciplinary approach. Addressing this complex relationship necessitates the establishment of a global research network. This perspective discusses the intricate interplay between physiological stress and environmental disease, focusing on common environmental diseases, cancer, diabetes, and cognitive degeneration. Furthermore, we highlight the intricate and reciprocal nature of the connection between physiological stress and these environmental diseases giving a perspective on the current state of knowledge as well as identifying where further information is necessary. Recognizing the role of physiological stress in environmental health outcomes will aid in the development of comprehensive strategies to safeguard public health and promote ecological balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Esterhuizen, Park, Kim, Kim, Yoon, Andres, Rodriguez-Rodriguez and Tanabe.)

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation of the methanolic extract of N. peltata roots led to the isolation of 15 compounds ( 1 - 15 ), which were structurally determined as α-spinasterol ( 1 ), 3- O - β -D-glucopyranosyl-oleanolic acid 28- O - β -D-glucuronopyranoside ( 2 ), 4-hydroxybenzoic acid ( 3 ), protocatechuic acid ( 4 ), vanillic acid ( 5 ), p -coumaric acid ( 6 ), caffeic acid ( 7 ), ferulic acid ( 8 ), neochlorogenic acid (neo-CQA) ( 9 ), chlorogenic acid (CQA) ( 10 ), cryptochlorogenic acid (crypto-CQA) ( 11 ), isochlorogenic acid B (3,4-DCQA) ( 12 ), isochlorogenic acid A (3,5-DCQA) ( 13 ), isochlorogenic acid C (4,5-DCQA) ( 14 ), and 3,4,5-tri- O -caffeoylquinic acid (TCQA) ( 15 ). Of these 15 compounds, compound 2 was a new oleanane saponin, the chemical structure of which was characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry (HRESIMS), as well as chemical reaction. Biological evaluation of the isolated compounds revealed that 3,4,5-tri- O -caffeoylquinic acid (TCQA) significantly improved Nrf2 levels in an Nrf2-ARE reporter HaCaT cell screening assay. TCQA was found to potently inhibit the Nrf2/HO-1 pathway and to possess strong anti-wrinkle activity by modulating the MAPK/NF-κB/AP-1 signaling pathway and thus inhibiting MMP-1 synthesis in HaCaT cells exposed to UVB. Our results suggest that TCQA isolated from N. peltata might be useful for developing effective antioxidant and anti-wrinkle agents.

In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.

Hydrogels are used in wound dressings because of their tissue-like softness and biocompatibility. However, the clinical translation of hydrogels remains challenging because of their long-term stability, water swellability, and poor tissue adhesiveness. Here, tannic acid (TA) is introduced into a double network (DN) hydrogel consisting of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) to realize a tough, self-healable, nonswellable, conformally tissue-adhesive, hemostatic, and antibacterial hydrogel. The TA within the DN hydrogel forms a dynamic network, enabling rapid self-healing (within 5 min) and offering effective energy dissipation for toughness and viscoelasticity. Furthermore, the hydrophobic moieties of TA provide a water-shielding effect, rendering the hydrogel nonswellable. A simple chemical modification to the hydrogel further strengthens its interfacial adhesion with tissues (shear strength of ≈31 kPa). Interestingly, the TA also can serve as an effective hemostatic (blood-clotting index of 58.40 ± 1.5) and antibacterial component, which are required for a successful wound dressing. The antibacterial effects of the hydrogel are tested against Escherichia coli and Staphylococcus aureus. Finally, the hydrogel is prepared in patch form and applied to a mouse model to test in vivo biocompatibility and hemostatic performances., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The molecular mechanism of perfluorobutanesulfonic acid (PFBS), an alternative to legacy perfluorooctanesulfonic acid (PFOS), is not fully understood yet. Therefore, we conducted a developmental toxicity evaluation on zebrafish embryos exposed to PFBS and PFOS and assessed neurobehavioral changes at concentrations below each point of departure (POD) determined by embryonic mortality. Using transcriptomics, proteomics, and metabolomics, biomolecular perturbations in response to PFBS were profiled and then integrated for comparison with those for PFOS. Although PFBS (7525.47 μM POD) was approximately 700 times less toxic than PFOS (11.42 μM POD), altered neurobehavior patterns and affected kinds of endogenous neurochemicals were similar between PFBS and PFOS at the corresponding POD-based concentrations. Multi-omics analysis revealed that the PFBS neurotoxicity mechanism was associated with oxidative stress, lipid metabolism, and glycolysis/glucogenesis. The commonalities in developmental neurotoxicity-related mechanisms between PFBS and PFOS interconnected by knowledge-based integration of multi-omics included the calcium signaling pathway, lipid homeostasis, and primary bile acid biosynthesis. Despite being less toxic than PFOS, PFBS exhibited similar dysregulated molecular mechanisms, suggesting that chain length differences do not affect the intrinsic toxicity mechanism. Overall, carefully managing potential toxicity of PFBS can secure its status as an alternative to PFOS., 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 © 2023 Elsevier B.V. All rights reserved.)

Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided., Competing Interests: CONFLICT OF INTEREST: Young-Kyun Lee has been an editorial board member since January 2023, but had no role in the decision to publish this article. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Hip Society.)

Herein, a standalone software equipped with a graphic user interface (GUI) is developed to predict liquid chromatography mass spectrometry (LC-MS) retention times (RTs) of dansylated metabolites. Dansylation metabolomics strategy developed by Li et al. narrows down a vast chemical space of metabolites into the metabolites containing amines and phenolic hydroxyls. Combined with differential isotope labeling, e.g., 12 C-reagent labeled individual samples spiked with a 13 C-reagent labeled reference or pooled sample, LC-MS analysis of the dansylated samples enables accurate relative quantification of all labeled metabolites. Herein, the LC-RTs for dansylated metabolites are predicted using an artificial neural network (ANN) machine-learning model. For the ANN modeling, 315 dansylated urine metabolites obtained from the DnsID database are used. The ANN LC-RT prediction model was reliable, with a mean absolute deviation of 0.74 min for the 30 min LC run. In the RT model, a deviation of more than 2 min was observed in only 3.2% of the total 315 metabolites, while a deviation of 1.5 min or more was observed in 11% of the metabolites. Furthermore, it was found that the LC-RT prediction was also reliable even for metabolites containing both amine and phenolic functional groups that can undergo dansylation on either one of the two functional groups, resulting in the generation of two isomeric forms. This RT-prediction model is embedded into a user-friendly GUI and can be used for identifying nontargeted dansylated metabolites with unknown RTs, along with accurate mass measurements. Furthermore, it is demonstrated that the developed software can help identify metabolites from a urine sample of an anonymous healthy pregnant woman., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyzes, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. 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 © 2023 Elsevier B.V. All rights reserved.)

Mori Folium ( Morus alba leaf, MF) and Mori Cortex Radicis ( Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1 , Ppargc1a , Cbp/p300-interacting transactivator ( Cited ), Prdm16 , Tbx1 , and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

Enteropathogenic bacteria express two-component systems (TCSs) to sense and respond to host environments, developing resistance to host innate immune systems like cationic antimicrobial peptides (CAMPs). Although an opportunistic human pathogen Vibrio vulnificus shows intrinsic resistance to the CAMP-like polymyxin B (PMB), its TCSs responsible for resistance have barely been investigated. Here, a mutant exhibiting a reduced growth rate in the presence of PMB was screened from a random transposon mutant library of V. vulnificus, and response regulator CarR of the CarRS TCS was identified as essential for its PMB resistance. Transcriptome analysis revealed that CarR strongly activates the expression of the eptA , tolCV2 , and carRS operons. In particular, the eptA operon plays a major role in developing the CarR-mediated PMB resistance. Phosphorylation of CarR by the sensor kinase CarS is required for the regulation of its downstream genes, leading to the PMB resistance. Nevertheless, CarR directly binds to specific sequences in the upstream regions of the eptA and carRS operons, regardless of its phosphorylation. Notably, the CarRS TCS alters its own activation state by responding to several environmental stresses, including PMB, divalent cations, bile salts, and pH change. Furthermore, CarR modulates the resistance of V. vulnificus to bile salts and acidic pH among the stresses, as well as PMB. Altogether, this study suggests that the CarRS TCS, in responding to multiple host environmental signals, could provide V. vulnificus with the benefit of surviving within the host by enhancing its optimal fitness during infection. IMPORTANCE Enteropathogenic bacteria have evolved multiple TCSs to recognize and appropriately respond to host environments. CAMP is one of the inherent host barriers that the pathogens encounter during the course of infection. In this study, the CarRS TCS of V. vulnificus was found to develop resistance to PMB, a CAMP-like antimicrobial peptide, by directly activating the expression of the eptA operon. Although CarR binds to the upstream regions of the eptA and carRS operons regardless of phosphorylation, phosphorylation of CarR is required for the regulation of the operons, resulting in the PMB resistance. Furthermore, the CarRS TCS determines the resistance of V. vulnificus to bile salts and acidic pH by differentially regulating its own activation state in response to these environmental stresses. Altogether, the CarRS TCS responds to multiple host-related signals, and thus could enhance the survival of V. vulnificus within the host, leading to successful infection., Competing Interests: The authors declare no conflict of interest.

Background/objectives: The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage., Materials/methods: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks., Results: ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation., Conclusions: Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

To understand the mechanisms underlying tooth morphogenesis, we examined the developmental roles of important posttranslational modification, O-GlcNAcylation, which regulates protein stability and activity by the addition and removal of a single sugar (O-GlcNAc) to the serine or threonine residue of the intracellular proteins. Tissue and developmental stage-specific immunostaining results against O-GlcNAc and O-GlcNAc transferase (OGT) in developing tooth germs would suggest that O-GlcNAcylation is involved in tooth morphogenesis, particularly in the cap and secretory stage. To evaluate the developmental function of OGT-mediated O-GlcNAcylation, we employed an in vitro tooth germ culture method at E14.5, cap stage before secretory stage, for 1 and 2 days, with or without OSMI-1, a small molecule OGT inhibitor. To examine the mineralization levels and morphological changes, we performed renal capsule transplantation for one and three weeks after 2 days of in vitro culture at E14.5 with OSMI-1 treatment. After OGT inhibition, morphological and molecular alterations were examined using histology, immunohistochemistry, real-time quantitative polymerase chain reaction, in situ hybridization, scanning electron microscopy, and ground sectioning. Overall, inhibition of OGT resulted in altered cellular physiology, including proliferation, apoptosis, and epithelial rearrangements, with significant changes in the expression patterns of β-catenin, fibroblast growth factor 4 (fgf4), and sonic hedgehog (Shh). Moreover, renal capsule transplantation and immunolocalizations of Amelogenin and Nestin results revealed that OGT-inhibited tooth germs at cap stage exhibited with structural changes in cuspal morphogenesis, amelogenesis, and dentinogenesis of the mineralized tooth. Overall, we suggest that OGT-mediated O-GlcNAcylation regulates cell signaling and physiology in primary enamel knot during tooth development, thus playing an important role in mouse molar morphogenesis., (© 2023 Wiley Periodicals LLC.)