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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

Atopic dermatitis is a chronic skin disease affecting quality of life, sleep, and mental health. Traditional evaluation methods focus on clinical assessments, but there is a growing need for tools that incorporate patient-reported outcomes (PROs). To evaluate the effectiveness of the Atopic Dermatitis Control Tool (ADCT) in assessing disease severity in patients with moderate to severe atopic dermatitis and to compare the efficacy of systemic immunosuppressants and dupilumab in patients with moderate to severe atopic dermatitis. A prospective, observational study was conducted across seven centres in Korea, involving 112 patients with moderate to severe atopic dermatitis. The ADCT, Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI) were used for assessing atopic dermatitis severity. In addition, the study assessed the effectiveness of immunosuppressants and dupilumab over the course of one year. The study found significant correlations between ADCT scores and other severity measures (EASI, DLQI). The correlation coefficients were 0.54 (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.

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.

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 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.

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: 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.

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.

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.

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.

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.

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 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.

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.

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.

Background Oocyte retrieval is the most important procedure in in vitro fertilization (IVF). Various anesthetic methods are used to control a patient’s anxiety and pain during IVF; however, there are no recommended anesthetic methods at present. In this study, we retrospectively investigated chemical pregnancy rates according to the anesthetic method used for oocyte retrieval. Methods We reviewed records of patients who underwent oocyte retrieval between January 1, 2012 and December 31, 2017. Patients were divided into the spinal anesthesia (SA) and monitored anesthesia care (MAC) groups. The primary outcome was chemical pregnancy rate after IVF. Results The study included 95 patients. SA was administered in 77 (81%) and MAC in 18 (19%). The overall chemical pregnancy rate was 32.6% (31/95). According to the anesthetic method, the pregnancy rate was 32.5% (25/77) in the SA group and 33.3% (6/18) in the MAC group. There was no statistical difference in the pregnancy rate between the groups (P = 0.575). The procedural time was significantly shorter in the SA group than in the MAC group (P < 0.001). Conclusions Chemical pregnancy rates were not significantly different between the SA and MAC groups. However, the procedure duration was shorter in the SA group than in the MAC group.

Background: Preoperative autologous blood donation (PABD) is a conservation strategy for reducing allogenic blood transfusion (ABT) during minimally invasive cardiac surgery (MICS). We aimed to evaluate the effects of PABD on the frequency of ABT and clinical outcomes in patients undergoing MICS. Methods: We enrolled 113 patients (47.8±13.1 years, 50 men) undergoing MICS without preoperative anemia (hemoglobin ＞11 g/dL) between 2014 and 2017. Of these patients, 69 (the PABD group) donated autologous blood preoperatively and were compared to the non-PABD group (n=44). We analyzed the frequency of perioperative ABT and clinical outcomes. Results: Baseline characteristics did not significantly differ between groups, although preoperative hemoglobin levels were lower in the PABD group. All operations were performed using a minimally invasive approach. Patients’ surgical profiles were similar. There were no cases of mortality or significant differences in early postoperative outcomes. During the early postoperative period, hemoglobin levels were higher in the PABD group. No significant difference was found in the frequency of ABT. Conclusion: Although the PABD group had higher postoperative hemoglobin levels, there was no clear clinical benefit in the early postoperative period, despite a great deal of effort and additional cost. Additional PABD in the setting of strict policies for blood conservation was ineffective in reducing ABT for young and relatively healthy patients who underwent MICS.

Abstract Background Although β-lactam monotherapy may be sufficient in non-critically ill patients with community-acquired pneumonia, the value of combination antibiotic regimens in community-onset neutropenic pneumonia remains unclear. Methods A retrospective cohort study was conducted to compare the effects of combination antibiotic regimens to those of β-lactam monotherapy in cancer patients with community-onset neutropenic pneumonia. Electronic medical records of patients diagnosed with community-onset neutropenic pneumonia between March 1995 and February 2015 at a tertiary care center were reviewed. Results During the study period, 165 cancer patients with community-onset neutropenic pneumonia were identified. Seventy-two patients received β-lactam monotherapy and 93 received combination therapy (β-lactam plus either a macrolide or fluoroquinolone). Causative pathogens were identified in 27.9% of the patients, and only two were positive for atypical pathogens. Although 30-day mortality was higher in the β-lactam group (15.3% versus 4.3%; P = 0.015), combination therapy was not associated with a statistically significant survival benefit in the multivariate analysis (hazard ratio 0.85, 95% confidence interval 0.20–3.67; P = 0.827). Duration of neutropenia, C-reactive protein level, and Multinational Association for Supportive Care in Cancer risk index were significant factors for 30-day mortality. In a subgroup analysis of patients treated with cefepime, the most frequently used β-lactam (63.0%), combination therapy also showed no significant survival benefit. Conclusions Combination antibiotic regimens were not associated with a survival benefit over β-lactam monotherapy in the treatment of community-onset neutropenic pneumonia. Unnecessary combination therapy should be reconsidered in cancer patients who are at high risk for adverse drug reactions and colonization with multi-drug resistant organisms.

PurposeWe aimed to evaluate microvascular changes on optical coherence tomography angiography (OCTA) in patients with rhegmatogenous retinal detachment (RRD) who underwent silicone oil (SO) tamponade and compare changes according to macular involvement.MethodsThis retrospective study included 48 patients with unilateral RRD who underwent vitrectomy and SO tamponade and were stable after SO removal. Control data were obtained from the fellow healthy eye. Ophthalmic examinations, including best corrective visual acuity (BCVA) and OCTA, were conducted. Differences in vascular density (VD) in different sections of the macula and differences in the foveal avascular zone (FAZ) were analyzed between the affected eyes and control eyes. Subgroup analyses according to macular involvement were performed.ResultsBaseline BCVA and duration of SO tamponade were associated with postoperative BCVA (pConclusionSO tamponade could cause microvascular changes, especially in the nasal parafoveal area. The macular-off RRD group were affected more than the macular-on RRD group.

Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood–brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-κB of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases.

Abstract In this study, we examined the influence of the dispersion solvent in three dipropylene-glycol/water (DPG/water) mixtures, with DPG contents of 0, 50, and 100 wt%, on ionomer morphology and distribution, using dynamic light scattering (DLS) and molecular-dynamics (MD) simulation techniques. The DLS results reveal that Nafion-ionomer aggregation increases with decreasing DPG content of the solvent. Increasing the proportion of water in the solvent also led to a gradual decrease in the radius of gyration (Rg) of the Nafion ionomer due to its strong backbone hydrophobicity. Correspondingly, MD simulations predict Nafion-ionomer solvation energies of −147 ± 9 kcal/mol in water, −216 ± 21 kcal/mol in the DPG/water mixture, and −444 ± 9 kcal/mol in DPG. These results suggest that higher water contents in mixed DPG/water solvents result in increased Nafion-ionomer aggregation and the subsequent deterioration of its uniform dispersion in the solvent. Moreover, radial distribution functions (RDFs) reveal that the (-CF2CF2-) backbones of the Nafion ionomer are primarily enclosed by DPG molecules, whereas the sulfonate groups (SO3 −) of its side chains mostly interact with water molecules.

Introduction: During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. Methods: The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4 μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. Results: Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (

BackgroundRebaudioside A and erythritol are nonnutritive sweeteners. There have been several studies of their glycemic effects, but the outcomes remain controversial. The purpose of this study was to evaluate the glycemic effects of rebaudioside A and erythritol as a sweetener in people with glucose intolerance.MethodsThis trial evaluated the glycemic effect after 2 weeks of consumption of rebaudioside A and erythritol as sweeteners in a pre-diabetic population. The patients were evaluated for fructosamine, fasting plasma glucose, C-peptide, insulin, and 2-hour plasma glucose before and after consumption of sweetener. The primary outcome was a change in fructosamine levels from the baseline to the end of treatment. Secondary outcomes were the changes in levels of fasting plasma glucose and 2-hour plasma glucose.ResultsFrom the baseline to the end of experiment, the changes in fructosamine levels after consumption of rebaudioside A and erythritol, did not differ significantly (244.00±19.57 vs. 241.68±23.39 µmol/L, P=0.366). The change in levels from the baseline to end of the study for rebaudioside A and erythritol were fasting plasma glucose (102.56±10.72 vs. 101.32±9.20 mg/dL), 2-hour plasma glucose (154.92±54.53 vs. 141.92±42.22 mg/dL), insulin (7.56±4.29 vs. 7.20±5.12 IU/mL), and C-peptide (2.92±1.61 vs. 2.73±1.31 ng/mL), respectively, and also did not differ significantly (P>0.05 for all).ConclusionOur study suggests that consumption of rebaudioside A and erythritol does not alter the glucose homeostasis in people with glucose intolerance.

The photophysical properties of closo-ortho-carboranyl-based donor–acceptor dyads are known to be affected by the electronic environment of the carborane cage but the influence of the electronic environment of the donor moiety remains unclear. Herein, four 9-phenyl-9H-carbazole-based closo-ortho-carboranyl compounds (1F, 2P, 3M, and 4T), in which an o-carborane cage was appended at the C3-position of a 9-phenyl-9H-carbazole moiety bearing various functional groups, were synthesized and fully characterized using multinuclear nuclear magnetic resonance spectroscopy and elemental analysis. Furthermore, the solid-state molecular structures of 1F and 4T were determined by X-ray diffraction crystallography. For all the compounds, the lowest-energy absorption band exhibited a tail extending to 350 nm, attributable to the spin-allowed π–π* transition of the 9-phenyl-9H-carbazole moiety and weak intramolecular charge transfer (ICT) between the o-carborane and the carbazole group. These compounds showed intense yellowish emission (λem = ~540 nm) in rigid states (in tetrahydrofuran (THF) at 77 K and in films), whereas considerably weak emission was observed in THF at 298 K. Theoretical calculations on the first excited states (S1) of the compounds suggested that the strong emission bands can be assigned to the ICT transition involving the o-carborane. Furthermore, photoluminescence experiments in THF‒water mixtures demonstrated that aggregation-induced emission was responsible for the emission in rigid states. Intriguingly, the quantum yields and radiative decay constants in the film state were gradually enhanced with the increasing electron-donating ability of the substituent on the 9-phenyl group (‒F for 1F < ‒H for 2P < ‒CH3 for 3M < ‒C(CH3)3 for 4T). These features indicate that the ICT-based radiative decay process in rigid states is affected by the electronic environment of the 9-phenyl-9H-carbazole group. Consequently, the efficient ICT-based radiative decay of o-carboranyl compounds can be achieved by appending the o-carborane cage with electron-rich aromatic systems.

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

The structure of the isoflavone compound, 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one (5), was elucidated by 2D-NMR spectra, mass spectrum and single crystal X-ray crystallography. Compound 5, C19H16O6, was crystallized in the monoclinic space group P21/c with the cell parameters; a = 12.0654(5) Å, b =11.0666(5) Å, c = 23.9550(11) Å, β = 101.3757(16)°, V = 3135.7(2) Å3, and Z = 8. The asymmetric unit of compound 5 consists of two independent molecules 5I and 5II. Both molecules exhibit the disorder of each methylene group present in their 1,4-dioxane rings with relative occupancies of 0.599(10) (5I) and 0.812(9) (5II) for the major component A, and 0.401(10) (5I) and 0.188(9) (5II) for the minor component B, respectively. Each independent molecule revealed remarkable discrepancies in bond lengths, bond angles and dihedral angles in the disordered regions of 1,4-dioxane rings. The common feature of the molecules 5I and 5II are a chromone ring and a benzodioxin ring, which are more tilted towards each other in 5I than in 5II. An additional difference between the molecules is seen in the relative disposition of two methoxy substituents. In the crystal, the molecule 5II forms inversion dimers which are linked into chains along an a-axis direction by intermolecular C–H⋯O interactions. Additional C–H⋯O hydrogen bonds connected the molecules 5I and 5II each other to form a three-dimensional network. Hirshfeld surface analysis evaluated the relative intermolecular interactions which contribute to each crystal structure 5I and 5II. Western blot analysis demonstrated that compound 5 inhibited the TNFα-induced phosphorylation of IKKα/β, resulting in attenuating further downstream NF-κB signaling. A molecular docking study predicted the possible binding of compound 5 to the active site of IKKβ. Compound 5 showed an inhibitory effect on the clonogenicity of HCT116 human colon cancer cells. These results suggest that compound 5 can be used as a platform for the development of an anti-cancer agent targeting IKKα/β.

In the title molecule, C19H20O6, the dihedral angle formed by the benzene rings is 36.71 (2)°. The hydroxy group is involved in a weak intramolecular O—H...O hydrogen bond. In the crystal, two weak C—H...O hydrogen bonds link the molecules into chains along [001].

In the title compound, C21H24N2O4, the 1,4-dihydropyridine ring adopts a very flattened boat conformation, with the 3-pyridine substituent in an axial orientation. The pyridine ring is almost orthogonally twisted relative to the 1,4-dihydropyridine skeleton by 85.97 (2)°. In the crystal, pairs of N—H...O hydrogen bonds form inversion dimers enclosing R22(16) rings. Pairs of intermolecular N—H...O hydrogen bonds link the dimers into chains along [100].

The isoflavone compound 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-methoxy-4H-chromen-4-one (6) was prepared and structurally characterized using NMR, mass spectrum and X-ray crystallography. Compound 6, C18H14O5, was crystallized in the monoclinic space group P21/n with the cell parameters; a = 7.1869(4) Å, b = 10.2764(6) Å, c = 19.6771(10) Å, β = 99.442(2)°, V = 1433.57(14) Å3, Z = 4. In the title compound, the chromenone ring system is slightly twisted from planarity and the dihedral angle formed between the plane of the chromenone ring and benzene ring is 47.75°. Several intermolecular hydrogen bonds make the crystal stabilized in the three-dimensional structure, which was confirmed by Hirshfeld surface analysis. Density functional theory (DFT) calculations at the B3LYP/6-311++G(d,p) level were carried out and the calculated geometric parameters were compared with the experimental results. A frontier molecular orbital calculation was performed to reveal that the energy values of highest occupied molecular orbital (HOMO) and lowest un-occupied molecular orbital (LUMO) were −5.8223 eV and −1.8447 eV, and the HOMO–LUMO energy gap was 3.9783 eV. A clonogenic long-term survival assay of compound 6 against HCT116 human colon cancer cells showed an anti-cancer ability, with GI50 value of 24.9 μM. Docking experiments within the active sites of aurora kinase A and B were carried out to explain the anti-cancer property of compound 6.

Closo-o-carboranyl compounds bearing the ortho-type perfectly distorted or planar terphenyl rings (closo-DT and closo-PT, respectively) and their nido-derivatives (nido-DT and nido-PT, respectively) were synthesized and fully characterized using multinuclear NMR spectroscopy and elemental analysis. Although the emission spectra of both closo-compounds exhibited intriguing emission patterns in solution at 298 and 77 K, in the film state, closo-DT mainly exhibited a π-π* local excitation (LE)-based emission in the high-energy region, whereas closo-PT produced an intense emission in the low-energy region corresponding to an intramolecular charge transfer (ICT) transition. In particular, the positive solvatochromic effect of closo-PT and theoretical calculation results at the first excited (S1) optimized structure of both closo-compounds strongly suggest that these dual-emissive bands at the high- and low-energy can be assigned to each π-π* LE and ICT transition. Interestingly, both the nido-compounds, nido-DT and nido-PT, exhibited the only LE-based emission in solution at 298 K due to the anionic character of the nido-o-carborane cages, which cannot cause the ICT transitions. The specific emissive features of nido-compounds indicate that the emissive color of closo-PT in solution at 298 K is completely different from that of nido-PT. As a result, the deboronation of closo-PT upon exposure to increasing concentrations of fluoride anion exhibits a dramatic ratiometric color change from orange to deep blue via turn-off of the ICT-based emission. Consequently, the color change response of the luminescence by the alternation of the intrinsic electronic transitions via deboronation as well as the structural feature of terphenyl rings indicates the potential of the developed closo-o-carboranyl compounds that exhibit the intense ICT-based emission, as naked-eye-detectable chemodosimeters for fluoride ion sensing.

Here we investigated the expressions of apoptosis-associated genes known to induce programed cell death through mRNA expressions of two matrix metalloproteinases (MMPs) that are involved in the degradation of collagen and basal membrane in luteal cells cultured in the treatment media. Our results show that the activity of MMP-2 gelatinase was higher in the CL2 and CL1 of luteal phase, was gradually decreased in the CH2 and CH3 of luteal phase. In particular, the expressions of P4-r and survival-associated genes (IGFr, PI3K, AKT, and mTOR) were strongly induced during CL3 stage, whereas the levels of these genes in corpus luteum (CL) were lower during CL2 and CL1 stages. In the cultured lutein cells analyzed, we found that as MMPs increase, genes related to apoptosis (20α-hydroxy steroid dehydrogenase and caspase-3) also increase. In other words, the results for P4-r and survival-related gene expression patterns in the luteal cells were contrary to the MMPs activation results. These results indicate that active MMPs are differentially expressed to induce the expression of genes associated with programed cell death from the degrading luteal cells. Therefore, our results suggest that the MMPs activation may lead to luteal cell development or death.

In the title salt, C18H18N3O+·Cl−, the aminopyrimidine molecule is protonated at one of the pyrimidine N atoms. The chloride anion interacts with the protonated pyrimidine N—H group and one of the amino N—H groups through two N—H...Cl hydrogen bonds, forming a six-membered ring. The chloride anion interacts further with the other amino N—H group to form an additional N—H...Cl hydrogen bond, which links the molecules along [001] in a helical manner.