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Abstract Kidney fibrosis causes irreversible structural damage in chronic kidney disease and is characterized by aberrant extracellular matrix (ECM) accumulation. Although glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is a crucial enzyme involved in proline-rich protein synthesis, its role in kidney fibrosis remains unclear. The present study revealed that EPRS1 expression levels were increased in the fibrotic kidneys of patients and mice, especially in fibroblasts and proximal tubular epithelial cells, on the basis of single-cell analysis and immunostaining of fibrotic kidneys. Moreover, C57BL/6 EPRS1tm1b heterozygous knockout (Eprs1 +/−) and pharmacological EPRS1 inhibition with the first-in-class EPRS1 inhibitor DWN12088 protected against kidney fibrosis and dysfunction by preventing fibroblast activation and proximal tubular injury. Interestingly, in vitro assays demonstrated that EPRS1-mediated nontranslational pathways in addition to translational pathways under transforming growth factor β-treated conditions by phosphorylating SMAD family member 3 in fibroblasts and signal transducers and activators of transcription 3 in injured proximal tubules. EPRS1 knockdown and catalytic inhibition suppressed these pathways, preventing fibroblast activation, proliferation, and subsequent collagen production. Additionally, we revealed that EPRS1 caused mitochondrial damage in proximal tubules but that this damage was attenuated by EPRS1 inhibition. Our findings suggest that the EPRS1-mediated ECM accumulation induces kidney fibrosis via fibroblast activation and mitochondrial dysfunction. Therefore, targeting EPRS1 could be a potential therapeutic target for alleviating fibrotic injury in chronic kidney disease.

Objective The present study aimed to investigate the effectiveness of dietary β-mannanase supplementation on growth performance, intestinal morphology, digesta viscosity, and dietary nutrient utilization in broiler chickens through a meta-analysis. The effects were further examined by a meta-regression analysis with activity levels of β-mannanase in broiler diets. Methods A total of 23 studies, which were conducted in 11 countries and completed between December 2003 and August 2023, were selected for this meta-analysis. The standardized mean difference and its 95% confidence interval were calculated as the effect size metrics using random effect model, with I2 value being utilized to measure heterogeneity. Investigated measurements included body weight gain (BWG), feed intake, feed conversion ratio (FCR), villus height (VH), crypt depth (CD), VH:CD ratio, digesta viscosity, nitrogen-corrected metabolizable energy (AMEn), apparent ileal digestibility (AID), and apparent total tract retention (ATTR) of dry matter (DM), gross energy (GE), and nitrogen (N). All statistical analyses were performed using R version 4.3.3. Results Results revealed significant positive effects of dietary β-mannanase supplementation on BWG (p = 0.005), FCR (p

ABSTRACT: The current study aimed to investigate the effect of increasing supplementation of dietary glycine (Gly) on growth performance, meat quality, liver characteristics, and intestinal health in broiler chickens raised under heat stress (HS) conditions. A total of one thousand six hundred 25-d-old broiler chickens were randomly allotted to 1 of 5 dietary treatments with 8 replicates. Each replicate comprised 20 male and 20 female birds. A negative control (NC) diet was prepared to meet or exceed energy and nutrient requirement estimates, whereas a positive control (PC) diet was formulated to contain increasing concentrations of AMEn by 50 kcal/kg as well as those of digestible amino acids, total Ca, and available P by 10% compared with the respective concentrations in the NC diet. Three additional diets were prepared by supplementing the NC diet with 0.4, 0.8, or 1.6% Gly. All chickens were raised under cyclic HS conditions at 29°C ± 0.89°C for 10 h/d and 23°C ± 1.45°C for the remaining time over an 18-d feeding trial. Results indicated that broiler chickens fed the NC diet had a greater (P < 0.05) FCR than those fed the PC diet under HS conditions. Increasing supplementation of up to 1.6% Gly in diets decreased (linear, P < 0.001) FCR in broiler chickens. Increasing supplementation of dietary Gly tended to increase (linear, P = 0.070) water holding capacity in the breast meat. Increasing supplementation of dietary Gly decreased (linear, P < 0.05) serum aspartate aminotransferase concentrations and tended to decrease blood heterophil:lymphocyte (linear, P = 0.083) and liver malondialdehyde concentrations (quadratic, P = 0.084). A tendency for increased villus height (linear, P = 0.086) and a significant increase in villus height:crypt depth ratio and goblet cell numbers (linear, P < 0.05) were identified following increasing Gly supplementation. In conclusion, increasing supplementation of dietary Gly improved feed efficiency, meat quality, liver health, and intestinal morphology possibly by mitigating oxidative stress and stress response in broiler chickens raised under HS conditions.

The current study aimed to investigate the effect of decreasing P concentrations in diets and phytase supplementation on growth performance, stress response, and intestinal health in broiler chickens. A total of four hundred 8-d-old Ross broiler chicks were randomly allotted to 1 of 4 dietary treatments with 10 replicates. Three treatment diets were formulated to contain different concentrations of available P (aP): adequate P (0.44 % aP), low P (0.30 % aP), and very low P (0.10 % aP) levels. One additional diet was prepared by supplementing 1,000 FTU/kg phytase in very low-P diets to maintain its aP concentrations equal to those in low-P diets. The experiment lasted for 25 d. It was observed that growth performance and toe ash concentrations were decreased (P < 0.05) in birds fed very low-P diets compared with those fed other treatment diets. Birds fed very low-P diets exhibited a greater (P < 0.05) blood heterophil:lymphocyte ratio than those fed other treatment diets. Jejunal villus height in birds fed adequate P diets or low-P diets was greater (P < 0.05) than those fed very low-P diets or very low-P diets with phytase. The malondialdehyde concentrations in the jejunal mucosa were greater (P < 0.05) for very low-P treatment than for other treatments. The expression levels of IL-4 and OCLN in the jejunal mucosa were less (P < 0.05) for adequate P treatment than for low-P treatment and very low-P with phytase treatment. Expression levels of P transporter genes in the jejunal mucosa were not affected by dietary treatments. In conclusion, feeding very low-P diets impaired growth performance, bone development, and jejunal morphology in broiler chickens with elevated stress response and intestinal lipid peroxidation. However, feeding low-P diets or very low-P diets with phytase maintained bone development, stress response, and antioxidant status in broiler chickens. The gene expression of intestinal P transporters were not influenced by decreasing P concentrations in diets and phytase supplementation in very low-P diets under the current experimental condition.

Abstract Background Red pepper paste is a common ingredient used in food in Korea. The discrimination of the geographical origin of agricultural products is important to protect the agricultural industry and customers from the misinformation regarding the product origin. Several studies have attempted to identify the geographical origin of red pepper based on its characteristic features using diverse methods, such as inorganic elemental analysis. However, similar studies on red pepper pastes have not been conducted thus far. Results In, this study, we established methods based on inductively coupled plasma optical emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) for determining inorganic elements in red pepper pastes. The limit of detection (LOD) of ICP-AES was in the range of 0.006–0.531 mg∙kg−1 and the limit of quantification (LOQ) was 0.017–1.593 mg∙kg−1. In addition, LOD and LOQ ranges for ICP-MS were 0.001–1.553, and 0.002–5.176 μg∙kg−1, respectively. The concentrations of Ca, K, Mg, Na, P, S, Cr, Mn, Co, Ni, Cu, Ga, As, Sr, Zr, Mo, Pd, Cd, Sn, Sb, Ce, Pt, Pb, and U were high in the Korean red pepper paste. All the employed discrimination models could clearly distinguish between Korean and Chinese red pepper pastes. In particular, among the four different models, CDA showed the most accurate ability to discriminate the geological origin of Korean and Chinese red pepper paste compared to that achieved using the other models with 100% accuracy. Conclusions Based on, the findings of this study, the use of ICP-AES and ICP-MS analyses for discriminating the inorganic elements in food products in combination with the aforementioned statistical analysis models could help the mitigation of issues associated with the misinformation of the geographical origin of agricultural products, aiding customer protection. Graphical Abstract

Abstract Background White standard Dendranthema grandiflorum (D. grandiflorum) is widely used for ornamental purposes. The volatile organic components (VOCs) of D. grandiflorum vary depending on the geographical origin and cultivar, which influence the market value. Here, we applied headspace extraction coupled with gas chromatography–mass spectrometry (HS–GC–MS) for the first time to determine the different origins (Korea, China, Vietnam) of D. grandiflorum in three genotypes (Baekgang, Jinba, Iwa-no-hakusen) based on volatile fingerprints and to assess the correlation among the metabolites identified in Korean and non-Korean D. grandiflorum. Results A total of 41 VOCs, mainly monoterpenoids, sesquiterpenoids, alcohols, and fatty acids, were identified. Principal component analysis showed that instead of geographical origin, genotype influences D. grandiflorum fingerprints. Cultivar discrimination was mainly affected by the metabolites associated with the alpha-terpinyl cation pathway. The orthogonal partial least squares discriminant analysis model achieved 100% and 93.3% accuracies in the calibration and validation sets, respectively. The results of volcano plots and clustering analysis, sesquiterpenoids were significantly more abundant in non-Korean than in Korean, whereas monoterpenoids were abundant in Korean samples. Conclusions 41 makers confirmed robustness maintenance over two years. These findings can be useful for reliably identifying the geographical origin of D. grandiflorum and providing a comprehensive understanding of VOCs in D. grandiflorum cultivars grown in different countries of origins. Graphical Abstract

Abstract Background Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.

Probiotics, prebiotics, and synbiotics are known to improve aquatic animals' growth and health conditions. In this study, we investigated the effect of Bacillus sp. KRF-7 (KRF-7), Bacillus sp. PM8313 (PM8313), β-glucooligosaccharide (BGO), and their synbiotics on the growth, digestive physiology, immunity, and gut microbiota of abalone, Haliotis discus hannai. The control diet (CON) was sprayed with 108 CFU/g KRF-7 (PRO1) or PM8313 (PRO2) as probiotics, 0.10% BGO (PRE) as prebiotic, and their combinations (SYN1: PRO1 + BGO; SYN2: PRO2+ BGO) as synbiotic treatments. These diets (triplicates) were given once daily to the abalone (initial body weight: 1.32 ± 0.05 g, initial shell length: 21. 69 ± 0.19 mm) for 12 weeks. The results showed that the PRE diet induced a significant 15% shell length and body weight increase against the CON (SLGR: 45.77% vs. 53.04%; WGR: 182.77% vs. 210.22%), the highest among dietary supplements (P < 0.05). The level of IGF and IGFBP in the cell-free hemolymph, protein expression of IGF signaling, and gene expression of myosin heavy chain in the adductor muscle increased significantly (P < 0.05) following dietary supplementation. Correspondingly, PRE-, PRO1-, and PRO2-fed abalone had the highest trypsin, lipase, and amylase secretion in the hepatopancreas (P < 0.05) and increased histomorphometry (stomach epithelial thickness and intestinal villi height) (P < 0.05). Regarding antioxidative capacity and immunity, the hepatopancreatic expression of SOD, CAT, IRAK-4, NF-Kb, TNF-α, and β-defensin were significantly upregulated in abalone fed with dietary additives compared to the CON (P < 0.05). In terms of gut microbiota profile, PRE-fed abalone had a significant reduction in microbial richness (P < 0.05). The phylum level was similarly occupied, while a diet-specific core microbiota at the genus level was apparent. The findings illustrated that BGO, KRF-7, and PM8313 can be used in abalone aquaculture as growth-promoting and immune-stimulating supplements.

Background/Aims: Among several methods used to prevent endoscopic submucosal dissection (ESD) bleeding, the recently developed hemostatic powder (HP) has few technical limitations and is relatively easy-to-use. This study aimed to analyze the hemostatic effects and mechanisms of two HPs using a porcine upper gastrointestinal hemorrhage model. Methods: We evaluated HPs (Endospray and epidermal growth factor [EGF]-endospray) for adhesion, waterproofing ability, permeability, and absorption in vitro. ESD was performed to induce bleeding ulcers in the porcine stomachs. In a total of three pigs, three bleeding ulcers per animal were generated. Hemostasis and rebleeding were evaluated endoscopically. After 72 hours, the animals were sacrificed, and histologically analyzed. Results: The water absorption of HPs was over 20 times the initial value within 30 minutes. The gelated HPs completely blocked water penetration into the applied site within 5 minutes and strongly adhered to the Petri-dish surface for up to 6 hours. The initial hemostasis rates within 5 minutes were 33.3%, 100.0%, and 66.7%, and the rebleeding rates at 6 to 72 hours after HP application were 33.3%, 16.7%, and 33.3% (control, Endospray, and EGF-endospray groups, respectively). Histological analysis revealed the thickness of the regenerated mucosa (522.1, 514.5, and 680.3 μm) and the submucosal layer (1,510.3, 2,848.2, and 3,062.3 μm) and the number of newly formed blood vessels (15.3, 17.9, and 20.5) in the control, Endospray, and EGF-endospray groups, respectively. Conclusions: The endoscopic HPs demonstrated the ability to elicit effective initial hemostasis and the histological ulcer-healing effect of EGF in an animal model of hemorrhagic gastric ulcers.

Background: Research on the reproductive physiology of Water and Sika deer, an endemic in Korea, still needs to be completed. This study analyzed the ovarian development and morphological characteristics of wild Water deer and Sika deer. Methods: Water deer and Sika deer ovaries were collected from the Korean Peninsula and Russia–Korean Peninsula border during the estrus and pregnancy seasons, respectively. And, morphological and physiological analysis and immunohistochemistry were conducted to confirm the detection of Ca2+ and assess the morphological changes in the ovaries. Results: The results of morphological analysis of ovaries during pregnancy and estrus, the development of the corpus luteum and follicles of Water deer showed similar patterns to other mammals. In contrast, the corpus luteum of Sika deer differed in tissue morphology and composition from Water deer. Ca2+ related to tissue metabolism was detected in the theca cells zone of Water deer on the estrus and was highly detected in the luteum cells zone during pregnancy. The hormone receptor protein expression patterns were generally higher in the ovaries of Water deer on the estrus and the pregnancy than in Sika deer. The expression of LH receptor was relatively low in the lutein cell zone, unlikely that of Water deer. The expression of VEGF was also different from Water deer, and the response in Sika deer was relatively very low compared to Water deer in expressing all proteins-related development. Conclusions: Therefore, the results of the study were shown that the composition of the corpus luteum of Sika deer is not clear compared to Water deer, and there are many differences in the functional and morphological formation of the corpus luteum.

Abstract The use of an identical electrolyte in electrochemical metallization (ECM)-based neuron and synaptic devices has not yet been achieved due to their different resistive-switching characteristics. Herein, we describe ECM devices comprising the same ferroelectric PbZr0.52Ti0.48O3 (PZT) electrolyte, which can sustain both neuron and synaptic behavior depending on the identity of the active electrode. The Ag/PZT/La0.8Sr0.2MnO3 (LSMO) threshold switching memristor shows abrupt and volatile resistive switching characteristics, which lead to neuron devices with stochastic integration-and-fire behavior, auto-recovery, and rapid operation. In contrast, the Ni/PZT/LSMO memory switching memristor exhibits gradual, non-volatile resistive switching behavior, which leads to synaptic devices with a high on/off ratio, low on-state current, low variability, and spike-timing-dependent plasticity (STDP). The divergent behavior of the ECM devices is attributed to greater control of cation migration through the ultrathin ferroelectric PZT. Thus, ECM devices with an identical ferroelectric electrolyte offer promise as essential building blocks in the construction of high-performance neuromorphic computing systems.

Abstract Activation of hypoxia‐inducible factor 1α (HIF1α) contributes to blood‐retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor‐associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB‐U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium‐dependent protease calpain‐1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.

ABSTRACT: This study aimed to investigate the effect of increasing fat supplementation in diets on productive performance, egg quality, and fatty liver incidence in laying hens during the entire laying cycle. A total of three hundred eighty-four 18-wk-old Hy-Line Brown laying hens were randomly allotted to 1 of 3 dietary treatments with 8 replicates for a 52-wk feeding trial. Each replicate comprised 16 consecutive cages with 1 hen per cage. The experimental diets were prepared by supplementing 0, 1.5, or 3.0% tallow to a basal diet, but all nutrients and energy in 3 diets were formulated to be equalized according to the recommended nutrient and energy concentrations at each phase of laying hens. Results indicated that increasing fat supplementation in diets decreased (linear, P < 0.01) feed conversion ratio (FCR) by increased egg mass (linear, P < 0.05) but decreased feed intake (linear and quadratic, P < 0.05) in laying hens during overall periods. Increasing fat supplementation in diets decreased (linear and quadratic, P < 0.05) egg yolk color during overall periods. Increasing fat supplementation in diets had no effects on liver color and hemorrhagic score measured at 60 wk (phase 3) and 70 wk of age (phase 4) without affecting hepatic fat concentrations during overall periods. However, the relative abdominal fat weight in laying hens was increased (linear and quadratic, P < 0.05) during overall periods by increasing fat supplementation in diets. In conclusion, increasing fat supplementation up to 3.0% in diets improves FCR with no impacts on fatty liver incidence and economics in laying hens throughout the entire laying cycle.

Background Herpes zoster (HZ) is one of the most common cutaneous adverse reactions associated with the coronavirus disease 2019 (COVID-19) vaccine and has been widely reported. This study aimed to evaluate HZ following COVID-19 vaccination from the viewpoint of pain management. Methods A retrospective study was conducted on 42 patients with HZ who visited the pain clinic between August 2021 and October 2021. Medical records were reviewed to compare pain severity, treatment methods, treatment duration, and incidence rate of postherpetic neuralgia (PHN) in patients who received COVID-19 vaccination within 6 weeks prior to developing symptoms compared with other patients with HZ. Results Fourteen patients developed HZ within 6 weeks after vaccination and were significantly younger than the other HZ groups. There were no significant differences in the frequency of prodromal pain, location of pain, pain severity, treatment methods, treatment duration, or incidence of PHN compared with the other HZ groups. Conclusions COVID-19 vaccination-related HZ showed clinical features similar to those of the other HZ.

Background Pre-anesthetic evaluation is an important aspect of perioperative patient management. However, anesthesiologists often encounter challenges during anesthesia due to conditions that are not detected during pre-anesthetic evaluations. Case Case 1 involved a 74-year-old female patient scheduled for cranioplasty and meningioma excision. Severe pancytopenia was detected during anesthesia. Cranioplasty was only performed, the surgery was terminated, and drug-induced pancytopenia was diagnosed and treated. The pre-anesthetic test results were normal, except for anemia. Case 2 involved a 71-year-old male patient who discovered large ecchymosis during general anesthesia preparation in the operating room for choledochal cyst surgery. Surgery was canceled to evaluate the bleeding tendency, and acquired coagulation factor VIII deficiency was diagnosed and treated. The pre-anesthetic tests were normal, except for prolongation of the activated partial thromboplastin time. Conclusions Abrupt hematologic and hemostatic changes may occur during anesthesia even though pre-anesthetic evaluation findings are normal.

Abstract Background Rg3-ginsenoside, a protopanaxadiol saponin, is a well-known adaptogen used for the prevention of cancer and inflammation. However, despite its distinct biological activity, the concentration of Rg3 in the total ginseng extract is insufficient for therapeutic applications. This study aims to convert PPD-class of major ginsenosides into a mixture of minor ginsenoside, to analyze its immune-regulatory role in macrophage cells. Results Using heat and organic acid treatment, three major ginsenosides, Rc, Rd, and Rb1, were converted into a mixture of minor ginsenosides, GRg3-mix [Rg3(S), Rg3(R), Rg5, and Rk1]. Purity and content analysis of the transformed compound were performed using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), compared with their standards. Preceding with the anti-inflammatory activity of GRg3-mix, lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells were treated with various concentrations of GRg3-mix (6.25, 12.5, 25, and 50 μg/mL). The cell viability assay revealed that the level of cell proliferation was increased, while the nitric oxide (NO) assay showed that NO production decreased dose-dependently in activated RAW264.7 cells. The obtained results were compared to those of pure Rg3(S) ≥ 98% (6.25, 12.5, and 25 μg/mL). Preliminary analysis of the CCK-8 and NO assay demonstrated that GRg3-mix can be used as an anti-inflammatory mediator, but mRNA and protein expression levels were evaluated for further confirmation. The doses of GRg3-mix significantly suppressed the initially upregulated mRNA and protein expression of inflammation-related enzymes and cytokines, namely inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-κB), tumor necrosis factor (TNF-α), and interleukins (IL-6 and IL1B), as measured by reverse transcription-polymerase chain reaction and western blotting. Conclusions Our pilot data confirmed that the mixture of minor ginsenosides, namely GRg3-mix, has high anti-inflammatory activity and has an easy production procedure.

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick's disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied.

The lack of net magnetization in antiferromagnets makes them technologically promising, but it also makes detecting the spin orders challenging. Here, using electrical transport measurement, Song et al show how the planar Hall effect can detect different cluster magnetic multipoles in antiferromagnetic Nd2Ir2O7 film.

Asthma is a chronic inflammatory disease of the airways characterized by varying and recurrent symptoms, reversible airway obstruction, and bronchospasm. In this paper, clinical important studies on asthma published between March 2021 and February 2022 were reviewed. A study on the relationship between asthma and chronic rhinosinusitis, bronchiectasis, and hormone replacement therapy was published. A journal on the usefulness of fractional exhaled nitric oxide for the prediction of severe acute exacerbation was also introduced. Studies on the effect of inhaler, one of the most important treatments for asthma, were published. Studies on the control of severe asthma continued. Phase 2 and 3 studies of new biologics were also published. As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, many studies have explored the prevalence and mortality of COVID-19 infection in asthma patients.

The 5d pyrochlore iridate family (R2Ir2O7, where R is a rare earth ion) has garnered significant attention due to its topological properties, such as Weyl semimetallic phases and axion insulator. However, the investigation of these properties has been impeded by severe iridium loss during growth, which results in the formation of defects and impurities. Herein, we demonstrate a method for controlling impurities and defects in strained Nd2Ir2O7 (NIO-227) films by compensating for iridium loss during growth. By increasing the amount of IrO2 target ablated, we enhance the morphological quality and electrical transport properties of the fabricated films. Furthermore, our results show that the anomalous Hall effects of the films have a strong dependency on the amount of IrO2 target ablated, which is attributed to the structural inhomogeneity in the NIO-227 films. Our work provides a way to control defects and impurities and would promote the investigation of topological phases in the family R2Ir2O7.

Abstract Background Canine cloning technology based on somatic cell nuclear transfer (SCNT) combined with genome-editing tools such as CRISPR-Cas9 can be used to correct pathogenic mutations in purebred dogs or to generate animal models of disease. Results We constructed a CRISPR-Cas9 vector targeting canine DJ-1. Genome-edited canine fibroblasts were established using vector transfection and antibiotic selection. We performed canine SCNT using genome-edited fibroblasts and successfully generated two genome-edited dogs. Both genome-edited dogs had insertion-deletion mutations at the target locus, and DJ-1 expression was either downregulated or completely repressed. Conclusion SCNT successfully produced genome-edited dogs by using the CRISPR-Cas9 system for the first time.

Abstract Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient’s age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

IntroductionHouse dust mites (HDM) are regarded as essential environmental allergens not only in human, but also in canine atopic dermatitis (CAD), however, there are only a few studies on the influence of indoor HDM concentration on the disease.MethodsOur study analyzed the correlation between the indoor HDM concentration, the severity of CAD, and the residential environments in client-owned 35 AD and 13 healthy dogs. We measured the extent of CAD and severity index-04 (CADESI-04), pruritus visual analog scale (PVAS), and transepidermal water loss (TEWL), indoor relative humidity (RH) and analyzed the residential environment questionnaires to evaluate AD severity.ResultsThe Der f 1 concentration had an inverse association with TEWL, and no association with CADESI-04 and PVAS. The Der f 1 concentration was significantly high in the group living near the green area and 40% or higher RH.DiscussionOur results suggest two possibilities: (1) Living around green areas and maintaining an appropriate indoor climate may help to improve CAD clinical symptoms. (2) The HDM may contain endotoxin and when present in high concentrations in CAD, they play a preventive role by enhancing the skin barrier function. Further studies with a larger number of dogs may help further elucidate an association between CAD and Der f 1.

The necessity for additional macroalgal biomass is warranted amid the ongoing expansion of abalone aquaculture. In the current study, an in-depth investigation of the food value of Sargassum horneri as a replacement for Undaria pinnatifida on growth, body composition, body histology, gut microbiota, and the taste sensory profile of abalone Haliotis discus hannai was carried out. After a 12-week feeding trial, the results indicated that 25% replacement (SH25) induced the highest shell-growth performance and best feed utilization values, although there was no significant difference in weight-related growth parameters with the basal (no inclusion of S. horneri) and 50% replacement (SH50) diets. Interestingly, the highest protein content was detected in abalone fed the basal diet followed by SH25 and SH50. The high replacement of S. horneri in the diet showed signs of structural integrity loss in the digestive gland. The results from the pyrosequencing of the genomic DNA from the gut of the abalone indicated an insignificant difference in α-diversity parameters and only a clear boundary was observed between SH0 and SH100 diets based on principal coordinate analysis. The bacterial genera Psychrilobacter, Vibrio, and Mycoplasma predominantly occupied the gut of the abalone, although there is a difference in their relative abundance. The taste screening experiment through the use of an electronic tongue showed a comparable taste profile of the abalone and is independent of the diets given. The findings of the present study showed that S. horneri, up to 50% replacement of macroalgal ingredients, can be utilized in feed formulation for H. discus hannai. These, in turn, contribute to the expanding knowledge on the utilization of biofouling and non-traditional macroalgae for sustainable abalone aquaculture practices.

Typical bacterial symptoms, water-soaking brown and black leaf spots with yellow halo, were observed on watermelon seedlings in nursery and field of Gyeongnam and Jeonnam provinces. Bacterial isolates from the lesion showed strong pathogenicity on watermelon and zucchini. One of them was rod-shaped with 4 polar flagella by observation of transmission electron microscopy. They belonged to LOPAT group 1. The phylogenical trees with nucleotide sequences of 16S rRNA and multi-locus sequencing typing with the 4 house-keeping genes (gapA, gltA, gyrB, and rpoD) of the isolates showed they were highly homologous to Pseudomonas syringae pv. syringae and grouped together with them, indicating that they were appeared as P. syringae genomospecies group 1. Morphological, physiological, and genetical characteristics of the isolates suggested they are P. syringae pv. syringae. We believe this is the first report that P. syringae pv. syringae caused leaf spot disease on watermelon in the Republic of Korea.

The reduction in esters, nitriles, and imines requires harsh conditions (highly reactive reagents, high temperatures, and pressures) or complex metal-ligand catalytic systems. Catalysts comprising earth-abundant and less toxic elements are desirable from the perspective of green chemistry. In this study, we developed a green hydroboration protocol for the reduction in esters, nitriles, and imines at room temperature (25 °C) using pinacolborane as the reducing agent and a commercially available Grignard reagent as the catalyst. Screening of various alkyl magnesium halides revealed MeMgCl as the optimal catalyst for the reduction. The hydroboration and subsequent hydrolysis of various esters yielded corresponding alcohols over a short reaction time (~0.5 h). The hydroboration of nitriles and imines produced various primary and secondary amines in excellent yields. Chemoselective reduction and density functional theory calculations are also performed. The proposed green hydroboration protocol eliminates the requirements for complex ligand systems and elevated temperatures, providing an effective method for the reduction in esters, nitriles, and imines at room temperature.

Olive flounder (Paralichthys olivaceus) muscle satellite cells (OFMCs) were obtained by enzymatic primary cell isolation and the explant method. Enzymatic isolation yielded cells that reached 80% confluence within 8 days, compared to 15 days for the explant method. Optimal OFMC growth was observed in 20% fetal bovine serum at 28 °C with 0.8 mM CaCl2 and the basic fibroblast growth factor (BFGF) to enhance cell growth. OFMCs have become permanent cell lines through the spontaneous immortalization crisis at the 20th passage. Olive flounder skeletal muscle myoblasts were induced into a mitogen-poor medium containing 2% horse serum for differentiation; they fused to form multinucleate myotubes. The results indicated complete differentiation of myoblasts into myotubes; we also detected the expression of the myogenic regulatory factors myoD, myogenin, and desmin. Upregulation (Myogenin, desmin) and downregulation (MyoD) of muscle regulation factors confirmed the differentiation in OFMCs.

Abstract Background The present study extensively aimed to evaluate the underlying mechanism of the immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium (PLM). Methods To assess whether PLM influences the production of markers related to inflammation, Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with PLM (50, 100, 200, and 500 μg/mL). Splenocyte, thymus, peritoneal exudate cells (PEC), and peripheral blood mononuclear cells (PBMC) were isolated from the Balb/c mice treated with Korean red ginseng or PLM once a day for 5 weeks. Moreover, all mice except normal mice were stimulated with 10% proteose peptone (PP) treated 3 days before the sacrifice and 2% starch treated 2 days before the sacrifice. Subsequently, the cytotropic substance was evaluated by using flow cytometry analysis and ELISA assay. Results PLM200 treatment significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and inhibited the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α dose-dependently in the LPS-stimulated RAW264.7 cells. PLM200 supplementation showed a significant increase in IL-2, IL-12, and interferon (IFN)-γ production and upregulated the ratio of IFN-γ (T-helper type 1, Th1) to IL-4 (T-helper type 2, Th2) in splenocytes. After PLM200 treatment, the significant elevation of CD4+CD25+, CD4+&CD8+, and CD4+CD69+ treatment were detected in thymus. Moreover, CD4+ and CD4+CD69+ in PBMC and CD69+ in PEC were also shown in a significant increase. Conclusions Taken together, these results showed an immunomodulatory effect of PLM about an elevated INF-γ/IL4 ratio, as an index of Th1/Th2, as well as the anti-inflammatory effect in the LPS-stimulated RAW264.7 cells. Therefore, our findings demonstrate that PLM possesses immunostimulatory and anti-inflammatory effects.

Abstract Moving along with daily life, urban residents and commuters create characteristic spatiotemporal patterns which vary extensively with the time of day. These patterns are formed via traffic flows: accordingly, understanding the impact of transportation system is essential for urban planners to evaluate expected urban activities. To explore them, we examine specifically population distributions in Seoul City by analyzing hourly population data based on mobile phone location records in combination with a couple of indicators of the Seoul Subway system. Through clustering and principal component analyses, we first demonstrate that the spatial distribution of the population is categorized according to the time of day, i.e., night, daytime, and evening, variations across which reflect the morphology of land use. We then examine the influence of the subway system on the population, employing ridership and accessibility as indicators. Our linear regression analysis shows that both are associated with the daytime and the evening populations, which implies that only commercial activities are substantially coupled to the subway system. Further, we find that the distinctive difference of night population is encoded in the probability distributions; this is elucidated by means of a multiplicative growth model for the morphological evolution of Seoul, revealing decentralization of residential areas and centralization of commercial areas. This study sheds light on the interplay of a public transportation system and land use, which is of relevance to planners and policymakers wishing to develop neighborhoods in support of sustainable modes.

Metastasis of pleomorphic adenoma (PA) is rare and usually presented as a locoregional recurrence developed many years after excision of the primary tumor although the PA is the most common neoplasm in the parotid gland. We described a case of a 48-year-old male with a parotid tumor with multiple enlarged ipsilateral lymph nodes which suggested a malignancy. The tumors had been neither evaluated nor excised and preoperative evaluation revealed benign PA in both lesions. After the complete surgical excision, the final pathology was notable for benign PA with metastasis to regional lymph nodes. At 1 year follow up he was clinically and radiographically free of disease. This implies that pleomorphic adenoma can occur as initially metastasis to regional lymph node even though benign neoplasm.

Abstract Background Recently, the possibility of tumour classification based on genetic data has been investigated. However, genetic datasets are difficult to handle because of their massive size and complexity of manipulation. In the present study, we examined the diagnostic performance of machine learning applications using imaging-based classifications of oral squamous cell carcinoma (OSCC) gene sets. Methods RNA sequencing data from SCC tissues from various sites, including oral, non-oral head and neck, oesophageal, and cervical regions, were downloaded from The Cancer Genome Atlas (TCGA). The feature genes were extracted through a convolutional neural network (CNN) and machine learning, and the performance of each analysis was compared. Results The ability of the machine learning analysis to classify OSCC tumours was excellent. However, the tool exhibited poorer performance in discriminating histopathologically dissimilar cancers derived from the same type of tissue than in differentiating cancers of the same histopathologic type with different tissue origins, revealing that the differential gene expression pattern is a more important factor than the histopathologic features for differentiating cancer types. Conclusion The CNN-based diagnostic model and the visualisation methods using RNA sequencing data were useful for correctly categorising OSCC. The analysis showed differentially expressed genes in multiwise comparisons of various types of SCCs, such as KCNA10, FOSL2, and PRDM16, and extracted leader genes from pairwise comparisons were FGF20, DLC1, and ZNF705D.

Foot-and-mouth disease (FMD) is a highly infectious disease affecting cloven-hoofed animals and causes significant economic losses to the livestock industry. The Type O PanAsia-2 (O PA-2) vaccine strain is protective against a wide range of serotype O FMD virus (FMDV) strains in East Asia, and A22 Iraq/24/64 (A22 IRQ) is the most widely used vaccine strain in FMD vaccine antigen banks. The aim of this study was to produce antigens from O PA-2 and A22 IRQ viruses using a 100 L bioreactor and evaluate the protective efficacy of varying antigen concentrations in pigs. More than 2 μg/mL of the antigen was recovered from the O PA-2 and A22 IRQ virus-infected supernatants. Further, inactivation of O PA-2 and A22 IRQ by binary ethyleneimine revealed that the viral titers decreased below 10−7 TCID50/mL within 13 h and 9 h, respectively. The O PA-2 and A22 IRQ vaccines, containing 10 μg and 5 μg of antigen, respectively, provided protection against homologous viruses in pigs. This is the first report demonstrating that the antigens obtained from the pilot-scale production of O PA-2 and A22 IRQ are viable candidate vaccines. These results will pave the way for industrial-scale FMD vaccine production in South Korea.

Background The direct entry of the camera under the epiglottis may provide a better view of the glottis than the indirect lifting of the epiglottis by placing the Macintosh blade tip on the vallecula when using the video laryngoscope. This study aimed to compare the efficiency of two different methods of lifting the epiglottis during the visualization of glottis using video laryngoscopy in the same patient. Methods This prospective study enrolled 60 patients who underwent general anesthesia with tracheal intubation. In each patient, glottic views were obtained by directly (group DE) and indirectly lifting the epiglottis (group IE). These two methods were compared using the modified Cormack and Lehane grade and the percentage of glottis opening (POGO) score as assessment parameters. Results Modified Cormack and Lehane grade showed a significant difference between the groups DE and IE (P = 0.004). The difference in the POGO score between the groups DE and IE was also statistically significant (87.5% and 64.4%, respectively; P < 0.001). Conclusions Our results, therefore, revealed that the method of directly lifting epiglottis was better at exposing glottis than the method of indirectly lifting epiglottis using a video laryngoscope.

Although somatic cell nuclear transfer (SCNT) is frequently employed to produce cloned animals in laboratories, this technique is expensive and inefficient. Therefore, the handmade cloning (HMC) technique has been suggested to simplify and advance the cloning process, however, HMC wastes many oocytes and leads to mitochondrial heteroplasmy. To solve these problems, we propose a modified handmade cloning (mHMC) technique that uses simple laboratory equipment, i.e., a Pasteur pipette and an alcohol lamp, applying it to porcine embryo cloning. To validate the application of mHMC to pig cloning, embryos produced through SCNT and mHMC are compared using multiple methods, such as enucleation efficiency, oxidative stress, embryo developmental competence, and gene expression. The results show no significant differences between techniques except in the enucleation efficiency. The 8-cell and 16-cell embryo developmental competence and Oct4 expression levels exhibit significant differences. However, the blastocyst rate is not significantly different between mHMC and SCNT. This study verifies that cloned embryos derived from the two techniques exhibit similar generation and developmental competence. Thus, we suggest that mHMC could replace SCNT for simpler and cheaper porcine cloning.

Cumulus-oocyte complexes (COCs), which contain immature oocytes, are matured in vitro for in vitro embryo production. Oocyte and cumulus cells are then separated using hyaluronidase. To date, there have only been a few reported cases of the toxic effects of hyaluronidase on porcine oocytes. The aim of this study was to compare the effects of bovine testis-derived hyaluronidase and recombinant human hyaluronidase on oocyte denudation and quality. Porcine COCs were matured for 44 h and denuded using different hyaluronidase concentrations and exposure times. Then, oocytes were activated by electrical parthenogenesis. In experiment 1, COCs were denuded using bovine-derived, ovine-derived (Hirax), and human recombinant (ALT-BC4) hyaluronidases for 10 and 20 min. In experiment 2, bovine-derived and human recombinant (ALT-BC4 and ICSI Cumulase®) hyaluronidases were used to denude the COCs for 2 and 20 min. In both experiments the oocytes were all completely denuded, and there was no degeneration. Rate of embryo development was significantly increased in group treated ALT-BC4 for 2 min and not significantly different in other treatment groups. In general it slightly decreased with longer exposure times. These results have confirmed that different sources of hyaluronidase do not have detrimental effects on the quality of porcine oocytes and suggest that the human recombinant hyaluronidase ALT-BC4 is suitable for oocyte denudation with an increased blastocyst rate.

Background Interscalene brachial plexus block (ISBPB) is commonly used with general anesthesia for postoperative pain management in shoulder surgery. This study investigated the incidence of hypothermia and changes in the body temperature in patients undergoing arthroscopic shoulder surgery under ISBPB with propofol sedation. Methods This retrospective study enrolled 220 patients who underwent arthroscopic shoulder surgery. Patients were divided into general anesthesia (n = 34) and ISBPB with propofol sedation (n = 186) groups, and medical records were retrospectively compared. In addition, patients from the ISBPB group were further divided according to age (elderly [≥ 65 years], n = 98 vs. young [< 65 years], n = 88), and the incidence of hypothermia and changes in the body temperature were compared. Results Twenty-seven patients (12.3%) experienced perioperative hypothermia (range: 35.3–35.9℃). The incidence of perioperative hypothermia was 29.4% and 9.1% in the general anesthesia and ISBPB groups, respectively, and there was a significant difference between the two groups (P = 0.002). The incidence of perioperative hypothermia according to age in the ISBPB group was 9.2% and 9.1% in the elderly and young groups, respectively, and there was no significant difference between the two groups (P = 0.983). Conclusions The incidence of perioperative hypothermia during arthroscopic shoulder surgery under ISBPB with propofol sedation is lower than that under general anesthesia. Furthermore, when using ISBPB with propofol sedation, the incidence of perioperative hypothermia in elderly patients is similar to that in younger patients.

Abstract Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

Background : : Proteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification. Methods : : Patients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains. Results : : A total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively). Conclusion : : Severity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.

Background Endoscopic procedures of the esophagus are more complicated than those of other regions of the gastrointestinal tract. They have a relatively long procedure time and high risk of complications, such as perforation and bleeding. Perforations that occur during the procedure can accompany pneumoperitoneum and pneumomediastinum through leakage of insufflation air and cause severe ventilatory impairment. Case A 58-year-old male patient underwent enucleation of leiomyoma in the esophagus using endoscopy under general anesthesia. Ventilatory impairment occurred 15 min after commencement of the procedure. Subsequently, subcutaneous emphysema and severe abdominal distension were observed. We suggested the possibility of microperforation during the procedure to the endoscopist, and he performed endoscopic clipping around the excision site of leiomyoma. Conclusions Providing anesthetic care by anesthesiologists during endoscopic procedures is considered necessary for patient safety. Complications of endoscopic procedures can be detected and managed early without sequelae during anesthetic care.

Background Herpes zoster ophthalmicus (HZO) is an infectious disease that results from the reactivation of latent varicella zoster virus in the ophthalmic branch of the trigeminal ganglia. HZO manifests with herpes zoster-like symptoms such as rash with or without signs of ocular involvement. Cavernous sinus thrombosis (CST) is a life-threatening condition accompanied by signs and symptoms involving the eyes and the cranial nerves. Case We report a case of septic cavernous sinus thrombosis (caused by Streptococcus constellatus subsp. constellatus) which was masked by the simultaneous occurrence of HZO in this patient, resulting in delayed diagnosis. Conclusions CST may be obscured by HZO, prompt diagnosis and treatment is necessary when such case arrive.

The present study investigated the immunomodulatory effects of extracts of Curcuma longa L. (CLE) and Carthamus tinctorius L. (CTE) on inflamed macrophages and immunosuppressed mouse models. RAW 264.7 Macrophage cells were treated with various concentrations of CLE, CTE, and CLE + CTE to observe cell viability and nitric oxide (NO) production. Results showed that all treatments inhibited NO production, with the CLE + CTE treatment showing the strongest inhibitory effect. Furthermore, expression levels of iNOS and COX-2 were more strongly downregulated by treatment with CLE + CTE via regulation of ERK 1/2 and p38 activation. Moreover, CLE + CTE significantly upregulated the viability of peritoneal cavity cells, natural killer (NK) cell activity, and NK cell-related cytokines expression. All treatments (CLE, CTE, CLE + CTE) upregulated body weights and NK cell activity. Taken together, our results provide scientific evidence for the synergic effect between CLE and CTE as a co-treatment for anti-inflammatory and immunomodulatory effects.

2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of the reticuloendothelial system, including the bone marrow (BM) and spleen, on positron emission tomography/computed tomography (PET/CT) has been shown to be a significant prognostic factor in diverse malignancies. However, the relationship between FDG uptake of the BM and spleen and histopathological findings, including the tumor immune microenvironment, has not been fully evaluated. This study aimed to investigate the relationship of FDG uptake in the BM and spleen with histopathological findings and recurrence-free survival (RFS) in patients with gastric cancer. Seventy patients with gastric cancer who underwent pre-operative FDG PET/CT and subsequent curative surgery were retrospectively enrolled. On image analysis, the BM-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) were measured from PET/CT images, and on immunohistochemical analysis, the densities of immune cell infiltration in the tumor tissue were graded. The BLR and SLR showed significant positive correlations with the grades of CD163 cell and CD8 cell infiltration in the tumor tissue, respectively (p < 0.05). In multivariate survival analysis, both BLR and SLR were significant predictors of RFS (p < 0.05). FDG uptake in the BM and spleen might be potential imaging biomarkers for evaluating tumor immune microenvironment conditions and predicting RFS in patients with gastric cancer.

Trophoblast cells of endometrium during bovine pregnancy with different characteristics undergo dynamic changes during uterine remodeling, which can be observed as continuous changes, as P4 secreted by the mother is replaced by placental hormones. In this context, the present study analyzed tissues’ morphological changes through uterine apoptosis during early pregnancy. In addition, the expression pattern associated with apoptosis genes and 20α-HSD was determined in the endometrium and caruncle tissues. The localization of 20α-HSD, VEGF, Casp3, and mTOR protein was also determined in endometrium and caruncle during early pregnancy. From around 30 days, caruncle trophoblast cells with very high invasiveness expanded the villus section as the gestation period progressed. The surrounding cells detached and reorganized into new cells. In addition, an analysis of the effect of apoptosis on cell reorganization in the caruncle revealed that the expression of 20α-HSD/Casp-3 signals in the villus section gradually increased from 30 to 90 days. However, on the 30th day, glandular epithelial cells occurred sporadically in the trophoblast cell section. Moreover, the apoptosis of trophoblast cells increased at 90 days. Taken together, the results of the present study show that changes in the uterus during early pregnancy promote changes during later pregnancy by inducing the reorganization through the stimulation of 20α-HSD and Casp-3, promoting uterine and caruncle tissues, unlike cell development mediated by hormone signaling.