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Abstract Melanoma is a serious type of skin cancer that originates from melanocytes. Rodent melanoma models have provided valuable insights into melanoma pathology; however, they often lack applicability to humans owing to genetic, anatomical, physiological, and metabolic differences. Herein, we developed a transgenic porcine melanoma model that closely resembles humans via somatic cell nuclear transfer (SCNT). Our model features the conditional oncogenes cassettes, TP53R167H and human BRAFV600E, controlled by melanocyte-specific CreER recombinase. After SCNT, transgenic embryos developed normally, with the capacity to develop porcine embryonic stem cells. Seven transgenic piglets with oncogene cassettes were born through embryo transfer. We demonstrated that Cre recombination-mediated oncogene activation remarkably triggered the mitogen-activated protein kinase pathway in vitro. Notably, intradermal injection of 4-hydroxytamoxifen activated oncogene cassettes in vivo, resulting in melanocytic lesions resembling hyperpigmented nevi with increased proliferative properties similar to early human melanomas. This melanoma-inducing system, heritably transmitted to offspring, supports large-scale studies. The novel porcine model provides a valuable tool for elucidating melanoma development and metastasis mechanism, advancing translational medicine, and facilitating preclinical evaluation of new anticancer drugs.

Abstract The Fabry-Pérot interferometer, a fundamental component in optoelectronic systems, offers interesting applications such as sensors, lasers, and filters. In this work, we show a tunable Fabry-Pérot cavity consisting of tunable Sagnac loop reflectors (SLRs) and phase shifters based on electrostatic microelectromechanical (MEMS) actuator. The fabrication process of the device is compatible with the standard wafer-level silicon photonics fabrication processes. This electrostatic actuation mechanism provides well-balanced, scalable pathways for efficient tuning methodologies. The extinction ratio of the continuously tunable SLRs’ reflectivity is larger than 20 dB. Full 2π phase shifting is achieved, and response times of all the components are less than 25 μs. Both actuators have extremely low static power, measuring under 20 fW and the energy needed for tuning is both below 20 pJ.

Abstract Pilot balloon palpation is still a commonly used method to evaluate cuff pressure of the endotracheal tube after intubation. This study determined whether the size of the tracheal tube influenced the accuracy of pilot balloon palpation. A prospective observational analysis of 208 patients intubated with an endotracheal tube of internal diameter (ID) 6.0 or 8.0 was conducted. An anesthesiologist judged the cuff pressure by manual pilot balloon palpation, and then measured the cuff pressure with a pressure gauge. Cuff pressure exceeding 20–30 cmH2O was defined as false recognition. The intracuff pressure was significantly higher in ID 6.0 tube than in the ID 8.0 tube (41.9 ± 18.8 cmH2O vs. 30.3 ± 11.9 cmH2O, p

Abstract The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.

Background : : This study aimed to identify chronicity predictors of pediatric primary immune thrombocytopenia (ITP). Methods : : This study retrospectively reviewed the medical records of patients with primary pediatric ITP admitted to a tertiary medical center between 2010 and 2021. Forty-five patients with a platelet count

Abstract Deubiquitinating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-κB activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-κB pathway by hydrolyzing K63-linked ubiquitin chains from NF-κB signaling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-κB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. Mass spectrometric analysis showed that OTUD1 binds KEAP1, and the N-terminal intrinsically disordered region of OTUD1, which contains an ETGE motif, is indispensable for the KEAP1-binding. Indeed, OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1 −/−-mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways.

In this study, we propose an optimization method for occupant protection systems using a machine learning technique. First, a crash simulation model was developed for a Euro NCAP MPDB frontal crash test condition. Second, a series of parametric simulations were performed using a THOR dummy model with varying occupant safety system design parameters, such as belt attachment locations, belt load limits, crash pulse, and so on. Third, metamodels were developed using neural networks to predict injury criteria for a given occupant safety system design. Fourth, the occupant safety system was optimized using metamodels, and the optimal design was verified using a subsequent crash simulation. Lastly, the effects of design variables on injury criteria were investigated using the Shapely method. The Euro NCAP score of the THOR dummy model was improved from 14.3 to 16 points. The main improvement resulted from a reduced risk of injury to the chest and leg regions. Higher D-ring and rearward anchor placements benefited the chest and leg regions, respectively, while a rear-loaded crash pulse was beneficial for both areas. The sensitivity analysis through the Shapley method quantitatively estimated the contribution of each design variable regarding improvements in injury metric values for the THOR dummy.

Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis–discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, γ-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD.

We have assessed the applicability of the thermal-hydraulic system analysis code, SPACE, to a small modular reactor called SMART. For the assessment, the experimental data from a scale-down integral-test facility, SMART-ITL, were used. It was conformed that the SPACE code unrealistically calculates the safety injection flow rate through the CMT and SIT during a small-break loss-of-coolant experiment. This unrealistic behavior was due to the overprediction of interfacial heat transfer at the steam-water interface in a vertically stratified flow in the tanks. In this study, a special thermal-hydraulic component model has been developed to realistically calculate the interfacial heat transfer when a strong non-equilibrium two-phase flow is formed in the CMT or SIT. Additionally, we developed a special heat structure model, which analytically calculates the heat transfer from the hot steam to the cold tank wall. The combination of two models for the tank are called the special component model. We assessed it using the SMART-ITL passive safety injection system (PSIS) test data. The results showed that the special component model well predicts the transient behaviors of the CMT and SIT.

Background A high hematocrit level in patients with erythrocytosis is linked with increased blood viscosity and increased risk of thromboembolism. Therefore, it is necessary to adequately lower the hematocrit level before performing a high-risk surgery. Case A 67-year-old male was scheduled for aortic valve replacement due to severe aortic stenosis. The preoperative hematocrit level of this patient was very high due to secondary polycythemia by hypoxia. We decided to perform acute normovolemic hemodilution after anesthetic induction to reduce the risk of thromboembolism in the patient. The patient was discharged after a successful surgery and a post-operative period without any side effects. Conclusions We estimate that patients with secondary polycythemia may benefit from acute normovolemic hemodilution to reduce their hematocrit levels while undergoing cardiac surgery using cardiopulmonary bypass. However, it is necessary to control the hematocrit level, since a significant decrease can cause side effects.

Acute kidney injury (AKI) is an inflammatory sequence. It can lead to distant organ injury, including damage to the central nervous system (CNS), mediated by increased circulating cytokines and other inflammatory mediators. It can also lead to increased blood–brain barrier (BBB) permeability. However, the effect of AKI on the inflammatory response of the brain has not yet been investigated. Therefore, we observed the effect of AKI on BBB permeability, microglia and astrocyte activation, and neuronal toxicity in the brain. The striatum and ventral midbrain, known to control overall movement, secrete the neurotransmitter dopamine. The activation of microglia and astrocytes present in this area causes neuro-degenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The activation of astrocytes and microglia in the hippocampus and cerebral cortex, which are responsible for important functions, including memory, learning, concentration, and language, can trigger nerve cell apoptosis. The activation of astrocytes and microglia at this site is also involved in the inflammatory response associated with the accumulation of beta-amyloid. In the situation of kidney ischemia reperfusion (IR)-induced AKI, activation of microglia and astrocytes were observed in the striatum, ventral midbrain, hippocampus, and cortex. However, neuronal cell death was not observed until 48 h.

Background and Objectives: The aim of this study was to evaluate the impact of sagittal imbalance based on pelvic incidence–lumbar lordosis (PI-LL) mismatch on the analgesic efficacy of epidural steroid injection in geriatric patients. Materials and Methods: Patients aged 65 years or older who received lumbar epidural steroid injections under fluoroscopy were enrolled. The cutoff of PI-LL mismatch >20° was used as an indicator of a marked sagittal imbalance. The cross-sectional area of the psoas and paraspinal muscles, as well as the paraspinal fat infiltration grade were measured. A 50% or more decrease in pain score at four weeks after injection was considered as good analgesia. Variables were compared between PI-LL ≤ 20° and >20° groups and multivariate analysis was used to identify factors related to pain relief after injection. Results: A total of 237 patients consisting of 150 and 87 patients in the PI-LL ≤ 20° and >20° groups, respectively, were finally analyzed. Female patients, patients with lumbar surgery history, and the smaller cross-sectional area of the psoas muscles were predominantly observed in patients with sagittal imbalance. There was no difference in analgesic outcome after injection according to the PI-LL mismatch (good analgesia 60.0 vs. 60.9%, p = 0.889). Multivariate analysis showed that pre-injection opioid use, moderate to severe foraminal stenosis, and high-graded paraspinal fat infiltration were significantly associated with poor analgesia after injection. Conclusions: There was no significant correlation between sagittal spinopelvic alignment and pain relief after lumbar epidural steroid injection for geriatric patients.

The oncogenic role of nuclear LIM domain only 2 (LMO2) as a transcriptional regulator is well established, but its function in the cytoplasm is largely unknown. Here, we identified LMO2 as a cytoplasmic activator for signal transducer and activator of transcription 3 (STAT3) signaling in glioma stem cells (GSCs) through biochemical and bioinformatics analyses. LMO2 increases STAT3 phosphorylation by interacting with glycoprotein 130 (gp130) and Janus kinases (JAKs). LMO2-driven activation of STAT3 signaling requires the LDB1 protein and leads to increased expression of an inhibitor of differentiation 1 (ID1), a master regulator of cancer stemness. Our findings indicate that the cytoplasmic LMO2-LDB1 complex plays a crucial role in the activation of the GSC signaling cascade via interaction with gp130 and JAK1/2. Thus, LMO2-LDB1 is a bona fide oncogenic protein complex that activates either the JAK-STAT signaling cascade in the cytoplasm or direct transcriptional regulation in the nucleus.

There is no consensus as to whether exposure to noise causes HTN. The objective of this study was to investigate the relationships between occupational noise exposure, pre- HyperTensioN (HTN) and HTN. The study subjects consisted of 107,407 workers who underwent annual special medical check-ups for workers from 2000 to 2004. The control group was an annual medical check-up cohort consisting of 152,790 workers examined over the same time period. The 1:1 nearest age matching of the two groups was done and multivariable logistic regressions were used to evaluate the effects of occupational noise on pre-HTN and HTN. The adjusted odds ratio (OR) of pre-HTN (OR 1.29, 95% CI 1.27–1.32) in noise-exposed workers was significantly higher than that in non-noised exposed workers. The adjusted OR of HTN (OR 1.42, 95% CI 1.38–1.45) in noise-exposed workers was significantly higher than that in non-noised exposed workers. According to this study, occupational noise exposure might be related to pre HTN and HTN.

Abstract Background Genetic engineering technology such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system provides a powerful tool for developing disease models and determining gene functions. Recent interests in canine cancer models have highlighted the necessity of developing genetic engineering tools for dogs. In this study, we attempted to generate optimized CRISPR/Cas9 system to target canine tumor protein 53 (TP53), one of the most crucial tumor suppressor genes, to establish TP53 knockout canine cells for canine cancer research. Results We constructed CRISPR/Cas9 vectors using each of three TP53 gene-targeting guide RNAs (gRNAs) with minimal off-target potential. After transfection, we obtained several clones of TP53 knockout cells containing “indel” mutations in the targeted locus which had infinite cellular life span, resistance to genotoxicity, and unstable genomic status in contrast to normal cells. Of the established TP53 knockout cells, TP53KO#30 cells targeted by TP53 gRNA #30 showed non-cancerous phenotypes without oncogenic activation both in vitro and in vivo. More importantly, no off-target alteration was detected in TP53KO#30 cells. We also tested the developmental capacity of TP53 knockout cells after application of the somatic cell nuclear transfer technique. Conclusions Our results indicated that TP53 in canine cells was effectively and specifically targeted by our CRISPR/Cas9 system. Thus, we suggest our CRISPR/Cas9-derived canine TP53 knockout cells as a useful platform to reveal novel oncogenic functions and effects of developing anti-cancer therapeutics.

Abstract Background The aim of this study was to examine the relationship between the provision of safety and health information (PSHI) and occupational injuries. Methods This study was based on data from the 4th Korean Working Conditions Survey (KWCS) (2014). The sample consisted of data from 24,527 wage workers and was divided into high-risk and low-risk groups, depending on the probability of occupational injury. The high-risk group included subjects who could cause harm to themselves or others due to errors during work. We applied chi-squared tests and logistic regression analyses to examine the relationship between PSHI and occupational injuries. Results In the high-risk group, workers with no PSHI showed an adjusted odds ratio of 1.81 for occupational injury (95% CI 1.33–2.47). In contrast, there was no statistically significant relationship between PSHI and the incidence of occupational injury in the low-risk group. Conclusions To prevent occupational injuries, multi-faceted approaches that take different levels of injury risk into account are needed. Among workers with a high risk of occupational injury, more a stringent safety education program is required.

Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.

Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44-positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compared with that in the control group (p

Background: The aim of this study is to assess the neurodevelopmental status of infant patients who underwent cardiac surgery in infancy and to investigate the factors affecting the neurodevelopmental status. Methods: This retrospective study included 108 patients who underwent cardiac surgery before the age of one. We used the Bayley Scales of Infant Development II to evaluate the neurodevelopmental status. All patients were analyzed according to the presence of the syndrome. Patients without the syndrome were analyzed according to the presence of brain lesions. Results: The mean mental developmental index (MDI) and the mean psychomotor developmental index (PDI) were 76.11 ± 20.17 and 65.95 ± 18.34, respectively, in the first evaluation, and 73.98 ± 22.53 and 69.48 ± 20.86, respectively, in the second evaluation. In the subgroup analysis, no significant difference was observed between the first evaluation and the second evaluation. Conclusions: No significant difference was observed in the degree of development of the patients in the two evaluation periods. Although the presence of syndrome, brain lesion, or gestational age affected the degree of developmental delay, more than half of the patients had developmental delay in the two evaluation periods in any of the subgroup. Therefore, the necessity of early screening and early rehabilitation intervention is emphasized.

Recent advances in somatic cell nuclear transfer (SCNT) in canines facilitate the production of canine transgenic models. Owing to the importance of stable and strong promoter activity in transgenic animals, we tested human elongation factor 1α (hEF1α) and cytomegalovirus (CMV) promoter sequences in SCNT transgenic dogs. After transfection, transgenic donor fibroblasts with the hEF1α-enhanced green fluorescence protein (EGFP) transgene were successfully isolated using fluorescence-activated cell sorting (FACS). We obtained four puppies, after SCNT, and identified three puppies as being transgenic using PCR analysis. Unexpectedly, EGFP regulated by hEF1α promoter was not observed at the organismal and cellular levels in these transgenic dogs. EGFP expression was rescued by the inhibition of DNA methyltransferases, implying that the hEF1α promoter is silenced by DNA methylation. Next, donor cells with CMV-EGFP transgene were successfully established and SCNT was performed. Three puppies of six born puppies were confirmed to be transgenic. Unlike hEF1α-regulated EGFP, CMV-regulated EGFP was strongly detectable at both the organismal and cellular levels in all transgenic dogs, even after 19 months. In conclusion, our study suggests that the CMV promoter is more suitable, than the hEF1α promoter, for stable transgene expression in SCNT-derived transgenic canine model.

Dysregulated glutamate signaling, leading to neuronal excitotoxicity and death, has been associated with neurodegenerative pathologies. 17β-estradiol (E2) is a human steroid hormone having a role in reproduction, sexual maturation, brain health and biological activities. The study aimed to explain the neuroprotective role of E2 against glutamate-induced ROS production, MAP kinase-dependent neuroinflammation, synaptic dysfunction and neurodegeneration in the cortex and hippocampus of postnatal day 7 rat brain. Biochemical and immunofluorescence analyses were applied. Our results showed that a single subcutaneous injection of glutamate (10 mg/kg) induced brain oxidative stress after 4 h by disturbing the homeostasis of glutathione (GSH) and revealed an upsurge in ROS and LPO levels and downregulated the expression of Nrf2 and HO-1 antioxidant protein. The glutamate-exposed P7 pups illustrated increased phosphorylation of stress-activated c-Jun N-terminal kinase (JNK) and p38 kinase (p38) and downregulated expression of P-Erk1/2. This was accompanied by pathological neuroinflammation as revealed by enhanced gliosis with upregulated expression of GFAP and Iba-1, and the activation of proinflammatory cytokines (TNF-α) in glutamate-injected P7 pups. Moreover, exogenous glutamate also reduced the expression of synaptic markers (PSD-95, SYP) and induced apoptotic neurodegeneration in the cortical and hippocampal regions by dysregulating the expression of Bax, Bcl-2 and caspase-3 in the developing rat brain. On the contrary, co-treatment of E2 (10 mg/kg) with glutamate significantly abrogated brain neuroinflammation, neurodegeneration and synapse loss by alleviating brain oxidative stress by upregulating the Nrf2/HO-1 antioxidant pathway and by deactivating pro-apoptotic P-JNK/P-p38 and activation of pro-survival P-Erk1/2 MAP kinase pathways. In brief, the data demonstrate the neuroprotective role of E2 against glutamate excitotoxicity-induced neurodegeneration. The study also encourages future studies investigating if E2 may be a potent neuroprotective and neurotherapeutic agent in different neurodegenerative diseases.

Brain injury is a significant risk factor for chronic gliosis and neurodegenerative diseases. Currently, no treatment is available for neuroinflammation caused by the action of glial cells following brain injury. In this study, we investigated the quinpirole-mediated activation of dopamine D2 receptors (D2R) in a mouse model of traumatic brain injury (TBI). We also investigated the neuroprotective effects of quinpirole (a D2R agonist) against glial cell-induced neuroinflammation secondary to TBI in adult mice. After the brain injury, we injected quinpirole into the TBI mice at a dose of 1 mg/kg daily intraperitoneally for 7 days. Our results showed suppression of D2R expression and deregulation of downstream signaling molecules in ipsilateral cortex and striatum after TBI on day 7. Quinpirole administration regulated D2R expression and significantly reduced glial cell-induced neuroinflammation via the D2R/Akt/glycogen synthase kinase 3 beta (GSK3-β) signaling pathway after TBI. Quinpirole treatment concomitantly attenuated increase in glial cells, neuronal apoptosis, synaptic dysfunction, and regulated proteins associated with the blood–brain barrier, together with the recovery of lesion volume in the TBI mouse model. Additionally, our in vitro results confirmed that quinpirole reversed the microglial condition media complex-mediated deleterious effects and regulated D2R levels in HT22 cells. This study showed that quinpirole administration after TBI reduced secondary brain injury-induced glial cell activation and neuroinflammation via regulation of the D2R/Akt/GSK3-β signaling pathways. Our study suggests that quinpirole may be a safe therapeutic agent against TBI-induced neurodegeneration.

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aβ1−42 (Aβ1−42, 5 μL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aβ1−42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aβ1−42-injected mice to a greater extent than the Aβ1−42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aβ1−42 infused mouse brains; interestingly, these markers were significantly reduced in the Aβ + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aβ1−42-treated mouse brains, whereas these markers were markedly reduced in the Aβ + ALA-cotreated group. Moreover, Aβ1−42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aβ1−42) in the mouse brains, whereas these proteins were markedly reduced in the Aβ + ALA-cotreated group. We also checked the effects of ALA against Aβ-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aβ-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aβ + ALA-cotreated mouse brains.

Laser scribing can be used to enhance the flexibility of polymer films for flexible device applications. To optimize the bending curvature by controlling the scribing parameters—the depth, number, and interval of the scribed grooves, finite element analysis was conducted on the bending tests of scribed polyethylene terephthalate films. Moreover, the influences of the parameters on the stress/strain near the grooves were investigated. The maximum stress/strain and curvature generally increased with an increase in depth, whereas these values decreased with an increase in number and intervals. However, to maintain the mechanical stability of the films, the parameters were limited. The optimization results revealed that the maximum value of the curvature was 2.6 mm −1 at depth = 40 and intervals = 25 μm, for number = 7. An empirical equation relating the curvature to depth and intervals was also provided. The results of the analysis are useful for the design of laser-scribed grooves on various polymer films, for the enhancement of their bending curvature, while minimizing the mechanical instability.

Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to verproside glucuronides (M1 and M2), verproside sulfates (M3 and M4), picroside II (M5), M5 glucuronide (M7), M5 sulfate (M9), isovanilloylcatalpol (M6), M6 glucuronide (M8), M6 sulfate (M10), 3,4-dihydroxybenzoic acid (M11), M11 glucuronide (M12), M11 sulfates (M13 and M14), 3-methyoxy-4-hydroxybenzoic acid (M15), M15 glucuronides (M17 and M18), M15 sulfate (M20), 3-hydroxy-4-methoxybenzoic acid (M16), M16 glucuronide (M19), and M16 sulfate (M21). Incubation of verproside with rat hepatocytes resulted in thirteen metabolites (M1–M11, M13, and M14). Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of verproside, the drug was recovered in bile (0.77% of dose) and urine (4.48% of dose), and O-methylation of verproside to picroside II (M5) and isovanilloylcatalpol (M6) followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of verproside in rats.

Objectives: This study aimed to find gender distinctions in terms of the sociology of the population; to determine work-related factors; to analyze gender differences in daily living, work, sports, and art performances; and to identify gender-related factors that limited performance of daily living and work activities. Methods: A questionnaire was designed that included disabilities of the arm, shoulder, and hand (DASH), accident history, disease history, work duration at current workplace, marital status, job satisfaction, job autonomy, and physical demands of the job. Out of 1,853 workers surveyed, 1,173 questionnaires (63.3%; 987 males, 186 females) included responses to DASH disability and DASH optional work and were judged acceptable for analysis. Results: Upper extremity functional limitation during work and daily living was higher for females than males. The limitations for males increased according to their household work time, accident history, work duration, job satisfaction, physical demand, and job autonomy. Meanwhile, female workers' upper extremity discomfort was influenced by their disease history, job satisfaction, and physical demands. In addition, the size of the company affected male workers’ upper extremity function, while marriage and hobbies influenced that of female workers. Conclusion: This study addressed sociodemographic factors and work-related factors that affect each gender’s upper extremity function during daily living and working activities. Each factor had a different influence. Further studies are needed to identify the effect that role changes, not being influenced by risks at work, have on musculoskeletal disorders.

Normal body tissue or lesion characteristics in T1 images have been evaluated; however, how external parameters effect the change in signal intensity by gadolinium-based contrast agent remains unknown. We investigated how contrast enhancement changed according to echo time (TE) in 3.0T magnetic resonance (MR) T1 imaging and determined the optimal settings for TE in contrast-enhanced T1 imaging. Since there are no guidelines regarding parameters for T1 enhancement when using MR-contrast agents, we analyzed results from varying TEs (between 25 and 7 msec) in both a phantom and clinical study. We obtained the following results: contrast percentage of fat to saline increased from 740.0–1003.6%, response start point increased from 30–90 mmol, max peak signal intensity increased from 1771–2425 a.u., max peak point increased from 2–4 mmol, enhancement percentage of the max peak signal intensity (MPSI) to saline increased from 1671.0–2065.2%, the average of SI on each mol as TE increased from 600.8–996.6 a.u., the average of SI as TE on each molar concentration increased from 378–845 a.u., the AEPSS increased from 44.3–140.3%, and the AEPSC increased from 224.3–647.8%. We confirmed that TE can affect contrast enhancement, and the lowest TE has faster and higher effects on contrast enhancement.

The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP). Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.