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Kwan-Sub Kim,1 Wu-Seop Lee,2 Haejun Cho,3 Sung-Min Shim,4 Soohyun Kwak,5 So-Young Ji,2 SangYoon Jeon,1 Yong-Min Kim61Department of Anesthesiology and Pain Medicine, Dongkang Medical Center, Ulsan, South Korea; 2Department of Plastic Surgery, Dongkang Medical Center, Ulsan, South Korea; 3Department of Medical Education, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Anesthesiology and Pain Medicine, Gangneung Asan Medical Center, University of Ulsan College of Medicine, Gangneung, South Korea; 5Department of Rehabilitation Medicine, Semin Hospital, Ulsan, South Korea; 6Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, Hong KongAbstract: Although various cases of neuralgia and its treatments have been reported, not enough evidence is present to recommend a single type of treatment as the most effective. The patient we have dealt with experienced significant interferences in his daily life due to chronic allodynia, but the symptom could not be resolved via previously reported treatments. We report a case of which a patient who presented infraorbital neuralgia after trauma was successfully treated by a novel treatment strategy. The patient was treated by applying infraorbital nerve block and pulsed radiofrequency cautery side by side. Through this report, we evaluate proper prevention and treatment strategies for patients who develop infraorbital neuralgia through similar etiologies.Keywords: pulsed radio frequency, infraorbital nerve block, orbital wall fracture, ultrasound-guided, stellate ganglion block

Background: Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status., Patients and Methods: We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care., Results: With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, P < .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, P < .001)., Conclusions: The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency., Objectives: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life., Methods: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway., Results: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1β), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks., Conclusions: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the trends in the usage of antimicrobial drugs by patients with pneumonia with prescriptions from long-term care (LTC) hospitals in the Republic of Korea., Method: This retrospective study was conducted from 2011 to 2022 using the National Health Insurance Review and Assessment Service claim data in Korea. We calculated antibiotic usage expressed as a daily defined dose (DDD) per 1000 patients per day (DID)., Results: The number of patients with pneumonia in LTC hospitals increased by 2.7 times, from 30,000 in 2011 to 79,000 in 2022. Furthermore, antibiotic consumption per episode by patients with pneumonia in LTC hospitals increased from 17.14 DDD in 2011 to 18.11 DDD in 2022. Among the Access, Watch, and Reserve classification groups, the Watch group showed the highest usage; further, the Access group showed a decreasing trend, whereas the Watch and Reserve groups showed an increasing trend (p < 0.01). In the Watch group, the most commonly used antibiotic was J01CR05 (piperacillin and beta-lactamase inhibitor), followed in order by J01DD04 (ceftriaxone), J01MA12 (levofloxacin), and J01DH02 (meropenem). In the Reserve group, J01XB01 (colistin) and J01AA12 (tigecycline) were commonly used., Conclusion: The antibiotics prescribed for pneumonia in LTC hospitals have continuously increased the use of broad-spectrum antibiotics. Accordingly, appropriate use of antibiotics in LTC hospital settings and assessment of antibiotics used are warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: We performed this study to investigate the effect of intraoperative brainstem auditory evoked potential (IBAEP) changes on the development of postoperative nausea and vomiting (PONV) after microvascular decompression (MVD) for neurovascular cross compression., Methods: A total of 373 consecutive cases were treated with MVD. The use of rescue antiemetics after surgery was used as an objective indicator of PONV. IBAEP monitoring was routinely performed in all., Results: The use of rescue antiemetics was significantly associated with female sex (OR = 3.427; 95% CI, 2.077-5.654; P < 0.001), PCA use (OR = 3.333; 95% CI, 1.861-5.104; P < 0.001), and operation time (OR = 1.017; 95% CI, 1.008-1.026; P < 0.001). A Wave V peak delay of more than 1.0 milliseconds showed a significant relation with the use of rescue antiemetics (OR = 1.787; 95% CI, 1.114-2.867; P = 0.016) and a strong significant relation with the use of rescue antiemetics more than 5 times (OR = 2.426; 95% CI, 1.372-4.290; P = 0.002)., Conclusions: A wave V peak delay of more than 1.0 milliseconds might have value as a predictor of PONV after MVD. More detailed neurophysiological studies will identify the exact pathophysiology underlying PONV after MVD., (Copyright © 2024. Published by Elsevier Inc.)

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN., (© 2024. The Author(s).)

Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the β-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-G i1 complexes bound to three agonists with divergent signaling profiles. Combined with functional assays, we have identified "twin hotspots" in APLNR as key determinants for signaling bias, guiding the rational design of two exclusive G-protein-biased agonists WN353 and WN561. Cryo-EM structures of WN353- and WN561-stimulated APLNR-G protein complexes further confirm that the designed ligands adopt the desired poses. Pathophysiological experiments have provided evidence that WN561 demonstrates superior therapeutic effects against cardiac hypertrophy and reduced adverse effects compared with the established APLNR agonists. In summary, our designed APLNR modulator may facilitate the development of next-generation cardiovascular medications., Competing Interests: Declaration of interests A patent describing the G-protein-biased agonists targeting APLNR has been filed by Zhejiang University listing Y.Z. (ZJU), W.-W.W., and S.-Y.J. as inventors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Postoperative nausea and vomiting (PONV) occurs frequently after microvascular decompression (MVD). Fentanyl, an opioid, is strongly related to the development of PONV, and ketorolac, a nonsteroidal anti-inflammatory drug, has been approved for postoperative pain management. However, how ketorolac-based patient-controlled analgesia (PCA) causes PONV or how its efficacy differs from that of fentanyl-based PCA after MVD is unclear. In this study, the authors compared ketorolac-based with fentanyl-based PCA in terms of the incidence and severity of PONV and analgesia after MVD., Methods: This prospective, double-blind, single-center, randomized controlled trial conducted from December 2021 to February 2023 included patients with MVD who were randomly allocated to the ketorolac- or fentanyl-based PCA group postoperatively. The incidence (primary outcome) and severity of PONV and rescue antiemetic requirements were determined during the first 48 hours postoperatively. Additionally, postoperative pain scores, rescue analgesic requirement, PCA usage, and satisfaction scores were assessed during the study period. PONV severity and postoperative pain scores were assessed using an 11-point numeric rating scale (0 = none, 10 = extremely). Satisfaction scores for PONV and pain were determined (0 = very dissatisfied, 10 = very satisfied). Categorical variables were analyzed using the chi-square or Fisher's exact test. Continuous variables were analyzed using the Student t-test or Mann-Whitney U-test based on normal distribution., Results: Of 185 screened patients, 91 were excluded based on predetermined exclusion criteria; 87 patients (43 in the ketorolac group and 44 in the fentanyl group) were analyzed and showed no significant differences in demographic data between groups. PONV incidence (48.8% vs 79.5%, p = 0.003) and severity (p = 0.004) were lower in the ketorolac-based PCA group than in the fentanyl-based PCA group. In the ketorolac group, there was a significant reduction in rescue antiemetic requirements compared with the fentanyl group (p = 0.049). The number of discontinuations was lower in the ketorolac-based PCA group than in the fentanyl-based PCA group (p = 0.001), whereas no significant differences in postoperative pain were found between the two groups., Conclusions: In patients with MVD, ketorolac-based PCA resulted in a decrease in PONV incidence and severity compared with fentanyl-based PCA, with analgesic effects similar to those of fentanyl-based PCA. This study provides clinical evidence that ketorolac-based PCA may be a valid alternative to fentanyl-based PCA in postoperative care.

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background/aim: Glioma is often refractory. The accumulation of amyloid beta (Aβ) in the brain is commonly associated with Alzheimer's disease (AD), but there are studies suggesting that Aβ has tumor suppressor potential. The aim of this study was to identify a novel, non-invasive candidate biomarker for histological prediction and prognostic assessment of glioma., Patients and Methods: Serum was prepared from blood samples collected preoperatively from 48 patients with WHO grade II-IV glioma between October 2004 and December 2017 at a single tertiary institution. The concentration of Aβ42 was measured using the SMCxPRO immunoassay (Merck). The clinical and histological characteristics of the patients, including molecular subtypes, were reviewed., Results: The mean age of the patients was 52.2±12.5 years. The mean value of serum Aβ42 concentration was 7.6±7.8 pg/ml in the anaplastic astrocytoma (WHO grade III) group and 6.4±6.5 pg/ml in the glioblastoma multiforme (WHO grade IV) group. The Negative epidermal growth factor receptor (EGFR) expression was associated with higher serum Aβ42 levels (p=0.020). Kaplan-Meier analysis demonstrated that patients with high serum Aβ42 (>11.78 pg/ml) had significantly longer progression-free survival (PFS) (p=0.038) and overall survival (OS) (p=0.018)., Conclusion: This study investigated serum Aβ42 levels as a potential biomarker for glioma. The results showed that low serum Aβ42 levels were associated with EGFR expression and poor PFS and OS. Overall, these findings suggest a potential role of Aβ42 as a prognostic marker in astrocytomas., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs., Methods: A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed., Results: The median age was 55 years old. The median tumor volume was 0.089 cm 3 , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm 3 , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration., Conclusions: Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and myogenin) and decreased the expression levels of E3 ubiquitin ligases (atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

Lactobacilli have been widely used as probiotics because of their benefits for intestinal health and physiological functions. Among a variety of Lactobacillus genera, Limosilactobacillus reuteri has been studied for its ability to exert anti-inflammatory functions and its role in controlling metabolic disorders, as well as the production of the antimicrobial compound reuterin. However, the effects and mechanisms of L. reuteri on enhancing immune responses in the immunosuppressed states have been relatively understudied. In this study, we isolated an immunomodulatory strain, namely, L. reuteri KBL346 (KBL346), from a fecal sample of a 3-month-old infant in Korea. We evaluated the immunostimulatory activity and hematopoietic function of KBL346 in macrophages and cyclophosphamide (CPA)-induced immunosuppressed mice. KBL346 increased the phagocytic activity against Candida albicans MYA-4788 in macrophages, and as biomarkers for this, increased secretions of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) were confirmed. Also, the secretions of innate cytokines (TNF-α, IL-1β, and IL-6) were increased. In CPA-induced immunosuppressed mice, KBL346 at a dosage of 10 10 CFU/kg protected against spleen injury and suppressed levels of immune-associated parameters, including NK cell activity, T and B lymphocyte proliferation, CD4 + and CD8 + T cell abundance, cytokines, and immunoglobulins in vivo. The effects were comparable or superior to those in the Korean red ginseng positive control group. Furthermore, the safety assessment of KBL346 as a probiotic was conducted by evaluating its antibiotic resistance, hemolytic activity, cytotoxicity, and metabolic characteristics. This study demonstrated the efficacy and safety of KBL346, which could potentially be used as a supplement to enhance the immune system.

Introduction: Pulsed field ablation (PFA) is a nonthermal ablative strategy that achieves cell death via electroporation. Herein, we investigated the preclinical safety and efficacy of PFA using two novel 8-French, 16-electrode spiral PFA/mapping catheters (ElePulse; CRC EP, Inc.)., Methods: Bipolar PFA (>1.8 kV) was performed using 30 s, single-shot, QRS-gated applications. Altogether, 94 atrial structures were ablated in 23 swine, one canine, and one ovine, including right and left atria and atrial appendages, pulmonary veins, and superior and inferior (IVC) vena cavae. We also examined the impact of PFA on the phrenic nerve (14 swine) and on a deviated esophagus after delivery of PFA from inside the IVC (five swine)., Results: All applications were single-shot without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle twitching/activation (mean acceleration: 0.05 m/s 2 ). There was a marked reduction in post-PFA versus pre-PFA atrial electrogram amplitude (0.17 ± 0.21 vs. 1.18 ± 1.08 mV; p < .0001). Lesion durability was demonstrated up to 3 months in all targeted tissues. Histologically, lesions were contiguous and transmural, except in the atrial appendage, and without any thermal effects. Magnetic resonance, gross, and histologic examinations of the brain, rete mirabile, and kidneys revealed no thromboembolism. No acute/long-term phrenic nerve dysfunction was encountered. Although within 2 h of ablation, histologic examinations of the esophagus revealed acute PFA-related changes in the muscular layer, these completely resolved by 21 ± 5 days., Conclusion: A novel, single-shot, spiral PFA system is capable of safely creating large, durable atrial lesions without significant adverse effects on the phrenic nerve or the esophagus., (© 2023 Wiley Periodicals LLC.)

The objectives of the present study were to determine the nutrient digestibility of fish meal, defatted black soldier fly larvae (BSFL), and adult flies and to develop equations for estimating in vitro nutrient digestibility of BSFL for pigs. in vitro digestion procedures were employed to mimic the digestion and absorption of nutrients in the pig intestine. Correlation coefficients between chemical composition and in vitro nutrient digestibility of BSFL were calculated. In Exp. 1, in vitro ileal digestibility (IVID) of dry matter (DM) and crude protein (CP) and in vitro total tract digestibility (IVTTD) of DM and organic matter in defatted BSFL meal were less ( p < 0.05) than those in fish meal but were greater ( p < 0.05) than those in adult flies. In Exp. 2, CP concentrations in BSFL were negatively correlated with ether extract ( r = -0.91) concentration but positively correlated with acid detergent fiber (ADF; r = 0.98) and chitin ( r = 0.95) concentrations. ADF and chitin concentrations in BSFL were negatively correlated with IVID of DM ( r = -0.98 and -0.88) and IVTTD of DM ( r = -1.00 and -0.94) and organic matter ( r = -0.99 and -0.98). Prediction equations for in vitro nutrient digestibility of BSFL were developed: IVID of CP (%) = -0.95 × ADF (% DM) + 95 ( r 2 = 0.75 and p = 0.058) and IVTTD of DM (%) = -2.09 × ADF + 113 ( r 2 = 0.99 and p < 0.001). The present in vitro experiments suggest that defatted BSFL meal was less digestible than fish meal but was more digestible than adult flies, and nutrient digestibility of BSFL can be predicted using ADF as an independent variable., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2023 Korean Society of Animal Science and Technology.)

Environmental exposure to urban particulate matter (UPM) is a serious health concern worldwide. Although several studies have linked UPM to ocular diseases, no study has reported effects of UPM exposure on senescence in retinal cells. Therefore, this study aimed to investigate the effects of UPM on senescence and regulatory signaling in human retinal pigment epithelial ARPE-19 cells. Our study demonstrated that UPM significantly promoted senescence, with increased senescence-associated β-galactosidase activity. Moreover, both mRNA and protein levels of senescence markers (p16 and p21) and the senescence-associated secretory phenotype, including IL-1β, matrix metalloproteinase-1, and -3 were upregulated. Notably, UPM increased mitochondrial reactive oxygen species-dependent nuclear factor-kappa B (NF-κB) activation during senescence. In contrast, use of NF-κB inhibitor Bay 11-7082 reduced the level of senescence markers. Taken together, our results provide the first in vitro preliminary evidence that UPM induces senescence by promoting mitochondrial oxidative stress-mediated NF-κB activation in ARPE-19 cells., 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.)

Although many studies have been conducted on the use of median and transverse incisions in various surgeries in the field of human medicine, related studies in veterinary medicine are lacking. This study aimed to present treatment options for dogs requiring cholecystectomy by reporting the pros and cons of 121 cholecystectomies performed via transverse incision at our hospital over 10 years. In most included cases, nonelective cholecystectomy was performed in an unstable emergency situation. The perioperative mortality rate was 23.14%, which was not significantly different from that of cholecystectomy performed via the conventional midline approach. However, the overall operation time (46.24 ± 6.13 min; range 35-65 min) was shortened by securing an adequate surgical field of view. The transverse incision approach facilitates fast and accurate surgery without increasing the fatality rate in small-breed dogs, in whom securing an adequate surgical field of view is difficult. Thus, transverse incision should be actively considered in dogs undergoing cholecystectomy due to emergency conditions, such as bile leakage or biliary tract obstruction, since prolonged anesthesia can be burdensome. This study may improve cholecystectomy outcomes in small-breed dogs with difficult-to-secure surgical fields.

Objective: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards., Materials and Methods: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t., Results: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%)., Conclusion: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area., Competing Interests: Seung Hong Choi, a contributing editor of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Background: Monosodium urate (MSU) crystals are associated with gouty inflammatory diseases. MSU-associated inflammation is majorly triggered by NOD-like receptor protein 3 (NLRP3) inflammasome that promotes interleukin (IL)-1β secretion. Although diallyl trisulfide (DATS) is well-known polysulfide garlic compounds with anti-inflammatory effects, its action in MSU-induced inflammasome activation has not been known yet., Purpose: The objective of the current study was to investigate anti-inflammasome effects and mechanisms of DATS in RAW 264.7 and bone marrow-derived macrophages (BMDM)., Methods: The concentrations of IL-1β were analyzed with enzyme-linked immunosorbent assay. The MSU-induced mitochondrial damage and reactive oxygen species (ROS) production were detected by fluorescence microscope and flow cytometry. The protein expressions of NLRP3 signaling molecules, NADPH oxidase (NOX) 3/4 were assessed with Western blotting., Results: DATS suppressed MSU-induced IL-1β and caspase-1 accompanied by decreased inflammasome complex formation in RAW 264.7 and BMDM. In addition, DATS restored mitochondrial damage. DATS downregulated NOX 3/4 that were upregulated by MSU as predicted by gene microarray and confirmed by Western blotting., Conclusion: This study first reports mechanistic finding that DATS alleviates MSU-induced NLRP3 inflammasome by mediating NOX3/4-dependent mitochondrial ROS production in macrophages in vitro and ex vivo, suggesting DATS could be effective therapeutic candidate for gouty inflammatory condition., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Phloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from Ecklonia cava , a brown alga belonging to the family Laminariaceae , has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (H 2 O 2 )-induced oxidative damage in murine-derived C2C12 myoblasts. Our results revealed that phloroglucinol suppressed H 2 O 2 -induced cytotoxicity and DNA damage while blocking the production of reactive oxygen species. We also found that phloroglucinol protected cells from the induction of apoptosis associated with mitochondrial impairment caused by H 2 O 2 treatment. Furthermore, phloroglucinol enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) as well as the expression and activity of heme oxygenase-1 (HO-1). However, such anti-apoptotic and cytoprotective effects of phloroglucinol were greatly abolished by the HO-1 inhibitor, suggesting that phloroglucinol could increase the Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress. Taken together, our results indicate that phloroglucinol has a strong antioxidant activity as an Nrf2 activator and may have therapeutic benefits for oxidative-stress-mediated muscle disease.

Background/objectives: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH., Materials/methods: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated., Results: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone., Conclusions: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway., 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.)

Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba ( U. alba ) was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E 2 , and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively. Using immunofluorescence staining combined with western blot analysis, the activation of NF-κB was further investigated. NRF2 activity was also measured using a luciferase reporter assay. UaB abrogated protein and mRNA expressions of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages, thereby suppressing the production of proinflammatory mediators and cytokines. This was further validated when a concentration-dependent decrease in NO and ROS production was observed in zebrafish ( Danio rerio ) larvae. UaB also increased NRF2 activity in HaCaT/ARE cell line and attenuated NF-κB activation by inhibiting the nuclear translocation of transcription factor p65 in RAW 264.7 macrophages. Nontargeted LC-MS analysis of UaB revealed the presence of the flavonols quercitrin ( 1 ), quercetin ( 2 ), rutin ( 3 ), kaempferol ( 4 ), and kaempferol 3- O -rutinoside ( 5 ). Molecular docking indicates that major flavonol aglycones have high affinity toward COX-2 NSAID-binding sites, TNF-α, and TNF-α converting enzyme, while the glycosylated flavonoids showed strong binding toward iNOS and IKK-all possessing dynamic stability when performing molecular dynamics simulations at 140 ns. This is the first report to have elucidated the mechanistic anti-inflammatory potential of the Philippine endemic plant U. alba ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: Rathke's cleft cysts (RCCs) are nonneoplastic cysts. Most of them are asymptomatic and stable; when symptomatic, RCCs are surgically fenestrated and drained. However, the outcomes remain unclear. The authors evaluated the outcomes of RCC decompression., Methods: Between 2004 and 2019, 32 RCCs were decompressed in a single tertiary institution. The clinical characteristics, intraoperative findings, postoperative complications, and endocrinological and surgical outcomes were retrospectively reviewed. Patients who underwent sequential imaging at least twice and at least 12 months after surgery were included in the analysis., Results: Patients' mean age was 40.8±14.9 years, and 62.5% were women. The mean follow-up duration was 62.3±48.6 months. In 21 patients (65.6%), no residual cysts were identified on postoperative magnetic resonance imaging. Of the 18 patients with preoperative visual field defects, 17 (94.4%) experienced postoperative visual improvement. Postoperative complications included endocrinological deterioration in 11 patients (34.4%), permanent diabetes insipidus in 11 (34.4%), infection in four (12.5%), intrasellar hemorrhage in three (9.4%), and cerebrospinal fluid leak in two (6.3%). Follow-up images revealed cyst recurrence in nine patients (28.1%), an average of 20.4 months after surgery; in three patients, the cysts were symptomatic, and resection was repeated. Multivariable analysis revealed that postoperative endocrinological deterioration was the only independent factor associated with cyst recurrence (p=0.028; hazard ratio, 6.800)., Conclusion: Our findings showed that although only cyst fenestration for decompression was performed to preserve pituitary function, more pituitary dysfunction occurred than expected. Besides, the postoperative hormonal deterioration itself acted as a risk factor for cyst recurrence. In conclusion, surgery for RCC should be more careful.

Purpose: Numerous studies have linked particulate matter2.5 (PM 2.5 ) to ocular surface diseases, but few studies have been conducted on the biological effect of PM 2.5 on the cornea. The objective of this study was to evaluate the harmful effect of PM2.5 on primary rat corneal epithelial cells (RCECs) in vitro and identify the toxic mechanism involved., Materials and Methods: Primary cultured RCECs were characterized by pan-cytokeratin (CK) staining. In PM2.5-exposed RCECs, cell viability, microarray gene expression, inflammatory cytokine levels, mitochondrial damage, DNA double-strand break, and signalling pathway were investigated., Results: Exposure to PM 2.5 induced cytotoxicity and morphological changes in RCECs. In addition, PM 2.5 markedly up-regulated pro-inflammatory mediators but down-regulated the wound healing-related transforming growth factor-β. Furthermore, PM 2.5 promoted mitochondrial reactive oxygen species (ROS) production and mediated cellular damage to mitochondria and DNA, whereas these cellular alterations induced by PM 2.5 were markedly suppressed by a potential ROS scavenger. Noteworthy, removal of ROS selectively down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation of the nuclear factor-κB (NF-κB) p65 in PM 2.5 -stimulated cells. Additionally, SB203580, a p38 MAPK inhibitor, markedly suppressed these PM 2.5 -mediated cellular dysfunctions., Conclusions: Taken together, our findings show that PM 2.5 can promote the ROS/p38 MAPK/NF-κB signalling pathway and lead to mitochondrial damage and DNA double-strand break, which is ultimately caused inflammation and cytotoxicity in RCECs. These findings indicate that the ROS/p38 MAPK/NF-κB signalling pathway is one mechanism involved in PM 2.5 -induced ocular surface disorders.

The ability to couple with multiple G protein subtypes, such as G s , G i/o , or G q/11 , by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G s protein, have been determined. However, no structure of class B GPCRs with G q/11 has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G 11 and G o . We compare these structures with the structure of CRF2R in complex with G s to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes., (© 2022. The Author(s).)

Objective: This prospective, randomized, double-blinded trial aimed to evaluate the efficacy and safety of prophylactic ramosetron administration against postoperative nausea and vomiting (PONV) in patients undergoing microvascular decompression (MVD)., Methods: In this study, 100 patients undergoing MVD were randomly allocated to the control (normal saline, 2 mL) or ramosetron (ramosetron, 0.3 mg) groups at the end of surgery. The incidence and severity of PONV, need for rescue antiemetics, patient satisfaction score, duration of hospital stay, and the occurrence of adverse events were evaluated 48 hours post-surgery., Results: Data obtained from 97 patients were included in the final analysis. The incidence of PONV was significantly lower in the ramosetron group than in the control group throughout the 48-hour postoperative period (29.2% vs. 51.0%, p=0.028). A similar trend was observed with regard to PONV severity (p=0.041). The need for rescue antiemetics, satisfaction score, duration of hospital stays, and the occurrence of adverse events did not significantly differ between the groups., Conclusion: Prophylactic ramosetron administration reduced the incidence and severity of PONV in patients undergoing MVD without causing serious adverse events. Thus, ramosetron use may improve patient recovery following MVD.

A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd 2+ due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cd 2+ coordination, and the resulting optical signal changes make the ratiometric detection of Cd 2+ possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd 2+ removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd 2+ removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd 2+ , and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs., 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 © 2022 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to determine whether dietary black soldier fly (Hermetia illucens, HI) larvae oil (HILO) could serve as an alternative fat source to soybean oil (SBO) in laying hen diets., Methods: We randomly assigned 25-week-old Hy-line Brown laying hens (n = 144) to receive (n = 6 hens/group; eight replicates) a control or an experimental diet in which SBO was replaced with 50% (50HILO) or 100% HILO (100HILO)., Results: Dietary HILO did not negatively affect body weight or productive performance during the study. The eggs also had similar quality parameters, proximate composition, and cholesterol levels. However, the yolk color index was significantly higher (p<0.01) in the 100HILO than in the other groups. Dietary HILO significantly altered the composition of fatty acids (FAs) in abdominal fat and eggs. Total saturated fatty acids (SFAs) and total polyunsaturated FAs (PUFAs) were significantly increased and decreased in the 50HILO and 100HILO groups, respectively, compared with those in the control group (p<0.001 and p<0.0001, respectively). Specifically, the medium-chain FAs lauric and myristic acids were remarkably increased in the abdominal fat of laying hens fed HILO (p<0.0001), whereas only myristic acid increased in eggs (p<0.0001). Undesirable heavy metal (aluminum, fluorine, arsenic, lead, mercury, and cadmium) concentrations were below permissible limits in eggs., Conclusion: We considered that HILO could be an alternative dietary fat to SBO for laying hens with maintained productive performance and good egg quality.

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to G s and G q , whereas CCK2R primarily couples to G q . Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G s signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G q complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain-gut axis., (© 2022. The Author(s).)

Objective: Intraoperative language mapping under general anesthesia is imperative for brain tumor surgery because awake surgery is not always feasible. Monitoring corticocortical evoked potential (CCEP) is known to be a useful method for tracking neuronal connectivity and localizing functional areas. The authors evaluated the clinical benefit of intraoperative CCEP monitoring for language function preservation in patients undergoing glioma surgery., Methods: Between January 2019 and June 2021, the authors performed a total of 29 consecutive glioma surgeries using CCEP monitoring under general anesthesia because of a risk of speech impairment; these were analyzed. Language area mapping was implemented by the anterior language area to posterior language area CCEP method for arcuate fasciculus mapping, and tumor resection was performed while avoiding the localized language areas. Language function before and after surgery was evaluated by the Controlled Oral Word Association Test (COWAT)., Results: Intraoperative CCEP was successfully monitored in 25 patients (86.2%), and a valid signal was undetectable in the other 4 patients. Language function evaluation was possible before and after surgery in a total of 20 patients. Overall, the preservation rate of language function was 65.0%, and the deterioration rate was 35.0% after tumor resection with CCEP monitoring. Among those 8 patients with preoperative COWAT scores ≥ 18, 5 patients (62.5%) successfully preserved their language function, with COWAT scores > 18 after tumor resection. Among the 12 patients with preoperative deteriorated language function (COWAT score < 18), 8 patients (66.7%) showed improvement or preserved language function after surgery., Conclusions: Intraoperative CCEP monitoring of the arcuate fasciculus is an acceptable technology for the preservation of language function under general anesthesia in glioma surgery in patients in whom awake surgery is not feasible.

Objective: The objective was to test additivity of digestible energy and nutrient concentrations in the hatchery byproduct mixture fed to nursery pigs., Methods: In the previous studies, energy, phosphorus, calcium, and amino acid digestibility of infertile eggs, unhatched eggs, culled chicks, and a mixture of 3 hatchery byproduct ingredients was determined in nursery pigs (initial body weight = 9.4 to 14.2 kg). An additivity test was conducted using these determined values., Results: No difference was observed between determined and predicted metabolizable energy values in the mixture (3,998 and 3,990 kcal/kg as-is basis, respectively). Measured standardized total tract digestible phosphorus in the mixture was less than the predicted value (4.5 vs 5.3 g/kg as-is basis, respectively; p<0.05). Measured standardized total tract digestible calcium in the mixture was greater compared with the predicted value (40.0 vs 31.7 g/kg as-is basis, respectively; p<0.05). Measured standardized ileal digestible tryptophan in the mixture was greater than the predicted value (3.7 vs 3.1 g/kg as-is basis, respectively; p<0.05) whereas other amino acid values were additive., Conclusion: Energy and most of amino acid concentrations in hatchery byproducts are additive in the mixture fed to nursery pigs.

Integrating magnetic and optical properties into a metal-organic framework (MOF) remains a great challenge. Herein, we have reasonably constructed two 3D magnetooptical MOFs by incorporating a [Ir III (ppy) 2 (bpy)] + -based fluorescent metalloligand and magnetic Ln III centers. The alternating arrangements of Δ- or Λ-[Ir III (ppy) 2 (bpy)] + endow these MOFs with enhanced optical properties. Moreover, the use of Dy III leads to field-induced slow magnetic relaxation. This work provides an effective strategy for the preparation of magnetooptical bifunctional MOFs.

Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors., (© 2022. The Author(s).)

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L . brevis BJ20 and L . plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.

This study investigated the effect of exposure to flutriafol based on residues in pigs. Pigs were exposed to different concentrations (0.313, 0.625, 3.125, 6.25, and 12.5 mg/kg bw/d, n=20) for 4 wk in different treatment groups. Serum biochemical analysis, residue levels, and histological analysis were conducted using the VetTest chemistry analyzer, liquid chromatography mass spectrometry, and Masson's trichrome staining, respectively. The body weight (initial and final) was not significantly different between groups. Parameters such as creatinine, blood urea nitrogen, alanine aminotransferase, and lipase levels were significantly different as compared to the control group. Flutriafol increased the residue limits in individual tissue of the pigs in a dose dependent manner. Flutriafol exposures indicated the presence of fibrosis, as confirmed from Masson's trichrome staining. These results suggest that flutriafol affects the morphology and serum levels in pigs. The dietary flutriafol levels can provide a basis for maximum residue limits and food safety for pork and related products., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Background/objectives: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages., Materials/methods: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E 2 (PGE 2 ), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model., Results: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE 2 , which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae., Conclusions: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (©2021 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Quantum defects have been shown to play an essential role in nonradiative recombination in metal halide perovskites (MHPs). Nonetheless, the processes of charge transfer assisted by defects are still ambiguous. Herein, we theoretically study the nonradiative multiphonon processes among different types of quantum defects in MHPs using Markvart's model for the induced mechanisms of electron-electron and electron-phonon interactions. We find that the charge carrier can transfer between the neighboring levels of the same type of shallow defects by multiphonon processes, but it will be distinctly suppressed with an increase in the defect depth. For the nonradiation multiphonon transitions between donor- and acceptor-like defects, the processes are very fast and not sensitive to the defect depth, which provides a possible explanation for the phenomenon of blinking of photoluminescence spectra. We also discuss the temperature dependence of these multiphonon processes and find that their variational trends depend on the comparison of the Huang-Rhys factor with the emitted phonon number. These theoretical results not only fill some of the gaps in defect-assisted nonradiative processes in the perovskite materials but also provide deeper physical insights into producing higher-performance perovskite-based devices.

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

This study estimated the effect of exposure to propiconazole through implementation and residues in finishing pigs. We analyzed the expression of fibrosis-related genes and performed histological analysis of the blood, liver, kidney, muscle, ileum, and fat tissues. The animals were exposed for 28 d to different concentrations of propiconazole (0.09, 0.44, 0.88, 4.41, and 8.82 mg/kg bw/d). Quantitative, gene expression, and histological analyses in tissues were performed using liquid chromatography mass spectrometry, real-time PCR, and Masson's trichrome staining, respectively. Final body weight did not differ among groups. However, genes involved in fibrosis were significantly differentially regulated in response to propiconazole concentrations. Glucose, alanine aminotransferase, and total bilirubin levels were significantly increased compared with those in the control group, while alkaline phosphatase level was decreased (p<0.05) after exposure to propiconazole. The residue limits of propiconazole were increased in the finishing phase at 4.41 and 8.82 mg/kg bw/d. The liver, kidney, and ileum showed blue staining after propiconazole treatment, confirmed by Masson's trichrome staining. In conclusion, these findings suggest that propiconazole exposure disturbs the expression of fibrosis-related genes. This study on dietary propiconazole in pigs can provide a basis for determining maximum residue limits and a better understanding of metabolism in pigs and meat products., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Objective: The objectives of the present study were to determine digestible energy (DE), metabolizable energy (ME), and standardized total tract digestibility (STTD) of phosphorus (P) in meat meal (MM) and to compare these values with those in fish meal (FM), and soybean meal (SBM) fed to pigs., Methods: Two experiments were conducted to determine energy concentrations and STTD of P in MM, FM, and SBM fed to growing pigs. In Exp. 1, DE and ME in the 3 test ingredients were measured using 24 barrows with initial body weight (BW) of 77.7±8.3 kg. A corn-based diet and 3 diets containing corn and 22% to 30% of each test ingredient were prepared. In Exp. 2, the STTD of P in the 3 test ingredients was measured using 24 barrows (90.9±6.6 kg BW). Three diets were formulated to contain each test ingredient as the sole source of P., Results: In Exp. 1, the DE and ME values in MM (3,310 and 2,856 kcal/kg dry matter [DM]) were less (p<0.05) than those in FM (4,121 and 3,572 kcal/kg DM) and SBM (4,390 and 4,032 kcal/kg DM). In Exp. 2, FM (64.3%) had greater (p<0.05) STTD of P than SBM (44.8%) with MM (55.8%) having intermediate STTD of P., Conclusion: The MM contains less energy concentrations compared with FM and SBM, and digestibility of phosphorus in MM does not differ from that in FM and SBM.

Mori Ramulus, the dried twigs of Morus alba L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H 2 O 2 ) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H 2 O 2 -induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H 2 O 2 -treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H 2 O 2 -triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome c release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H 2 O 2 . Furthermore, AEMR diminished H 2 O 2 -induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H 2 O 2 -induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H 2 O 2 -induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy.

Insects are a potential source of proteins and fats which can be incorporated into diets of broiler chickens. Accordingly, black soldier fly larvae oil (BSFLO) needs to be tested as an appropriate fat source to produce healthy chickens for consumers. Therefore, the objective of the present study was to evaluate the effects of the replacement of soybean oil (SBO) with BSFLO in broiler diets on intestinal health and blood profiles. A total of 210 one-day-old male broilers were randomly allocated to three dietary treatments (10 replicates of seven birds per group): a control diet and two experimental diets in which SBO was replaced with 50% (50 BSFLO) or 100% (100 BSFLO) BSFLO. At the end of the study (35 days), 18 birds (six broilers per treatment) were slaughtered to determine the intestinal morphology, digestibility, and volatile fatty acid (VFA) profile. Blood samples were collected from 24 randomly selected birds (eight broilers per treatment) to determine the blood profiles. BSFLO supplementation positively affected villus height but did not affect digestibility. BSFLO showed no adverse effects on the VFA and blood profiles. In conclusion, the results of this study suggest that SBO can be replaced by BSFLO without any adverse effects on broiler health., Competing Interests: The authors declare no conflict of interest.