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In this paper, quantitative analysis was performed focusing on the structural effect on the ferroelectric switching of ferroelectric thin-film transistors (FeTFTs). FeTFTs and ferroelectric capacitor (FeCap) test element groups (TEGs) were designed and fabricated, and positive-up-negative-down (PUND) measurements were performed to analyze the switching characteristics of ferroelectric films in various structures constituting an FeTFT. It was verified that TiN/HZO/a-IGZO/Mo (MFSM, FeTFT source/drain contact) mostly contributed to the memory operation of an FeTFT, while TiN/HZO/a-IGZO (MFS, FeTFT channel) exhibits one-time memory operation with irreversible polarization switching. In addition, the switching characteristics of MFSM and MFS were different from those of MFM, especially after a few cycles, related to the oxygen vacancy migration between a-IGZO channels and HZO films. The extracted 2 P r values for MFS, MFSM and TiN/HZO/Mo (MFM, FeTFT source/drain parasitic capacitor) were 38, 28 and 20 [μC cm -2 ], respectively. Based on the operation differences according to the device structure, it was found that irreversible switching in the MFS region (channel) causes a rapid decrease in the memory window after the first switching in an FeTFT and degradation of a-IGZO and HZO films in the MFSM region (contact) including oxygen vacancy exchange and related defect generation causes subthreshold slope increases and negative threshold voltage shifts as cycling stress was applied.

A hangover is a combination of negative mental and physical symptoms, such as headache, diarrhea, and loss of appetite, that occur after alcohol consumption and can vary depending on individual genetic and environmental factors. To quickly relieve these hangover symptoms, a new hangover relief compound called HK-GCM-H01 has been developed. This compound, HK-GCM-H01, consists of fermented rice germ extracts, yeast extract mixtures, cili extract powder, and concentrated nipafam powder, all of which are known to relieve hangover symptoms. The safety and clinical symptoms of HK-GCM-H01 were evaluated, along with the pharmacokinetic properties of alcohol and acetaldehyde after its administration. This study was conducted on 50 healthy Korean men using a randomized, double-blind, placebo-controlled, single-intake, crossover design. To evaluate clinical symptoms, Acute Hangover Scale and Alcohol Hangover Severity Scale were used, and the pharmacokinetic evaluation parameters included the maximum plasma concentration, the time to peak plasma concentration, the terminal half-life, and the area under the plasma concentration-time curve from X hours to Y hours. A significant reduction in clinical symptoms was observed after alcohol consumption in the group that consumed HK-GCM-H01 with added hangover relief compound, as was a significant decrease in blood exposure to acetaldehyde compared to the placebo group. There were no adverse events or significant changes in liver function indicators reported during the safety evaluation. These findings indicate that HK-GCM-H01 is safe and significantly reduces plasma concentrations of acetaldehyde, the main cause of hangover, suggesting that it improves hangover symptoms., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2024 Translational and Clinical Pharmacology.)

Due to the forensic aspects of drinking and exposure to toxic substances, more sophisticated quantitative technology is needed to quantify the concentration of ethyl alcohol and acetaldehyde in the blood. In this study, we developed a headspace gas chromatography tandem mass spectrometry method that could simultaneously detect ethyl alcohol and acetaldehyde in human plasma. Through a simple preparation process, ethyl alcohol and acetaldehyde were quickly detected within 4 min, and a lower limit of quantification (LLOQ) (20 and 0.2 µg/mL) was obtained; these results confirmed the suitability of the system. According to Food and Drug Administration guidelines, the linearity (correlation coefficient > 0.9996), intraday and intraday accuracy, precision, and both short- and long-term stability and freeze-thaw stability satisfied the evaluation criteria (within 100.0 ± 15.0% and 20.0% of the LLOQ). Carryover and batch size assessment for the evaluation of the sample influence during analysis also satisfied the evaluation criteria. A valid method was applied to the pharmacokinetics study, and the plasma from 43 subjects after oral administration of the placebo or HK-GCM-H01 was analyzed. The developed analysis method for ethyl alcohol and acetaldehyde in blood could be used in various fields, such as forensics and those requiring precise quantification., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2024 Translational and Clinical Pharmacology.)

A gas chromatography coupled to high-resolution mass spectrometry (GC-HR/MS) has been used as the standard method for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), which are regulated at screening and action levels in the environment. However, several alternative methods have been attempted due to the disadvantage of its high cost. Although a gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) has been used in a wide variety of sample matrices, showing that they are interchangeable, there has been a lack of comprehensive studies on statistical agreement with GC-HR/MS. In this study, a pairwise comparison of the total concentrations of PCDDs/Fs in 90 soil field samples obtained by two mass spectrometric methods was performed using the Passing-Bablok (P&B) regression and Bland-Altman (B&A) analysis for the method comparison. According to the result of the B&A analysis, the concentration range of PCDDs/Fs was between 98.2 and 1760 pg/g showed good agreement between two methods at the 95 % confidence level (CL). Although there was a large discrepancy between the two methods in the low concentrations (<16.5 pg/g of PCDDs/Fs), this result was similar to the P&B regression analysis. As the verification results by B&A and P&B regression analysis, the interchangeable concentration range between the two methods was confirmed to be adequate for the monitoring of PCDDs/Fs regulating levels in soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Concerns about dioxin-like compounds have increased; however, the monitoring of polychlorinated naphthalenes (PCNs) in food and the assessment of dietary intake remain limited. In this study, various foods were collected from Korean markets and analyzed for PCNs. Fishery products exhibited the highest mean concentration (48.0 pg/g ww) and toxic equivalent (TEQ) (0.0185 pg-TEQ/g ww). Agricultural products were the largest contributors (35.7%) to the total dietary intake of PCN TEQ , followed by livestock products (33.6%), fishery products (20.2%), and processed foods (10.5%). The mean intake of PCN TEQ for the Korean population was 0.901 pg-TEQ/day for males and 0.601 pg-TEQ/day for females. Generally, males and younger groups had higher daily intakes of PCN TEQ , but they did not exceed the tolerable weekly intakes. Nonetheless, it is important to manage potential health risks associated with PCNs and other dioxin-like compounds by identifying major food items contributing to PCN exposure and considering age and gender differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis., Methods: This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated., Findings: The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%., Implications: Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis., Clinicaltrials: gov identifier: NCT04967014., Competing Interests: Declaration of competing interest The authors have indicated that they have no conflicts of interest regarding the content of article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Charcot neuroarthropathy (CN) is a chronic degenerative disorder of bones and joints, mostly associated with diabetes mellitus and human immunodeficiency virus. CN of the upper limb is rare, with only 58 case reports identified on PubMed with the majority of cases being closely associated with syringomyelia. Very rarely, cervical spondylotic myelopathy (CSM) is associated with CN of the upper limb; with very few literature reporting this association. This case report presents a rare case of Charcot arthropathy of the shoulder caused by CSM. A 57-year-old female presented to the emergency department following trauma to the right shoulder. On clinical examination, there was evidence of tenderness, extensive swelling, and bruising with a lack of range of motion along with numbness in the right arm and legs. Through radiographic and laboratory investigations, a diagnosis of CN secondary to CSM was made. A reverse total shoulder arthroplasty was performed however, this was complicated at two weeks with an atraumatic glenoid fracture and dislocation. First-stage revision surgery was then performed to allow fracture healing pending second-stage revision surgery. This report provides insight into the very rare possibility of the association of CN of the shoulder with CSM. A review of the literature suggests reverse shoulder arthroplasty is the gold standard for cases of severe bone and soft tissue damage. When undergoing investigations for Charcot neuroarthropathy, physicians must undertake a full detailed history along with a detailed neurological examination and imaging of the cervical spine to not miss the association with CSM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Park et al.)

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 ​mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM)., Methods: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL)., Results: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438)., Conclusions: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m 2 ) in a subsequent larger study., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca 2+ ) and other metal ions, such as zinc (Zn 2+ ) and magnesium (Mg 2+ ), into the cytosol. This Ca 2+ influx at the presynaptic terminal triggers the release of Zn 2+ and glutamate to the postsynaptic terminal. Zn 2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn 2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn 2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn 2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn 2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence., Trial Registration: ClinicalTrials.gov Identifier: NCT06147908., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2024 Translational and Clinical Pharmacology.)

Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) were assessed in coastal sediments from industrial bays in South Korea to evaluate the pollution levels and their environmental impact. The mean sediment concentrations of Σ 17 PCDD/Fs, Σ 18 PCBs, and Σ 15 PCNs were 198 ± 140, 3427 ± 7037, and 85 ± 336 pg/g dw, respectively. Generally, pollutant concentrations in the inner bay were higher than those in the outer bay, indicating the influence of industrial emissions and harbor activities. The primary sources were identified as steel manufacturing and wastewater treatment plants for PCDD/Fs, harbor and shipbuilding activities for PCBs, and combustion-related sources for PCNs. Notably, PCDD/F concentrations exceeded sediment guideline values. The combined effects of PCDD/Fs and PCBs demonstrated adverse impacts on aquatic organisms. Hence, the release of toxic pollutants into the marine environment could have potential biological effects due to the combined impact of these various compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The extent of postoperative pain following transoral thyroidectomy is not well-understood and remains a subject of debate. This study aims to analyze and compare postoperative pain levels between patients undergoing transoral and conventional transcervical thyroidectomy., Methods: A prospective evaluation on postoperative pain was conducted in 310 patients undergoing conventional thyroidectomy and 194 undergoing transoral thyroidectomy. Pain levels were evaluated using the numerical rating scale (NRS, ranging from 0 to 10) through preoperative and postoperative questionnaires at specified time points: 1, 3, and 6 days, and 1 and 3 months following surgery. Propensity score-matched analysis was carried out based on six covariates: sex, age, body mass index, extent of thyroidectomy, tumor size, and central neck dissection., Results: After propensity score matching based on the six covariates, 121 patient pairs were identified from each group. Within this matched cohort, postoperative pain scores significantly worsened 1 day after surgery but showed progressive recovery up to 3 months post-surgery in both groups. The transoral group exhibited higher postoperative pain scores than the conventional group from day 1 (4.43 ± 2.6 vs. 3.11 ± 2.5, p < 0.001) to day 6 (1.76 ± 1.9 vs. 1.13 ± 1.6, p = 0.016) post-surgery, with no significant difference noted at 1 month. Among transoral procedures, pain scores were significantly higher for the endoscopic approach compared to the robotic approach on days 1 (5.52 ± 2.3 vs. 4.29 ± 2.3, p = 0.028) and 3 (3.52 ± 2.5 vs. 2.64 ± 2.0, p = 0.047) post-surgery., Conclusions: Postoperative pain was significantly higher in transoral thyroidectomy compared to conventional thyroidectomy up to 6 days post-surgery. Within the transoral group, the robotic procedure resulted in lower pain levels than the endoscopic approach during the early postoperative period., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Famotidine, an H 2 receptor antagonist (H 2 RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine., Materials and Methods: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses., Results: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (t max,ss ) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUC T,ss ) and maximum concentration of drug in plasma in steady state (C max,ss ) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively., Conclusion: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.

Long-term nationwide atmospheric monitoring of organochlorine pesticides (OCPs) was performed in South Korea during 2008-2017. Their occurrences, seasonal and temporal variability, sources, and effect of ambient temperature were investigated. The OCPs are pronounced with a mean concentration of total OCPs ranging from 5.2 to 256 pg/Sm 3 . However, a decrease of 54 % was observed in the mean concentration of total OCPs from 2008 to 2017 associated with regulatory actions. OCP concentrations did not show any variations between the different site types, and OCPs were ubiquitously present at all site types. The mean concentration of total OCPs in summer was two-fold higher than in winter. The concentrations of DRINs, DDTs, ENDOs, and HCHs were significantly higher in summer, but the concentrations of chlordane and heptachlor were higher in winter. The diagnostic ratios identified major sources as ongoing sources, past use, and atmospheric transport. Clausius Clapeyron plots strongly suggested the re-emission of α-endosulfan, β-endosulfan, α-HCH, and β-HCH, and ΔH sa (enthalpy of surface air exchange) values suggested the influence of the transport and/or new sources on aldrin, dieldrin, and chlordane. The occurrence of OCPs due to re-emissions, ongoing sources, and long-range atmospheric transport could be a challenge towards the complete phase-out of OCPs in South Korea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ex situ conservation is used to protect endangered wildlife. As captive and wild long-tailed gorals are known to be similar, individuals under ex situ conservation can be reintroduced into nature. However, there is no appropriate indicator to evaluate them. Here, we amplified the internal transcribed spacer 2 (ITS2) region and compared the gut ecological information (eco-information) of captive and wild long-tailed gorals. We validated the existing ITS86F and ITS4 universal primers using reference sequences of the National Center for Biotechnology Information (NCBI) and improved their matching rates. We compared the gut eco-information of captive and wild long-tailed gorals obtained through experiments using the improved primer pair and found that the gut ecological diversity of captive gorals was low. Based on this, we suggested that the gut eco-information can be used as an evaluation index before reintroducing captive long-tailed gorals. Furthermore, we identified four plant types from the gut eco-information of wild long-tailed gorals, which can be the additional food sources to enhance the reduced intestinal ecological diversity of the captive animals.

Background: CT-P47 is a candidate tocilizumab biosimilar. This study assessed the pharmacokinetic (PK) equivalence of CT-P47 and European Union-approved reference tocilizumab (EU-tocilizumab) in healthy Asian adults., Research Design and Methods: This double-blind, multicenter, parallel-group trial randomized healthy adults (1:1) to receive a single (162 mg/0.9 mL) subcutaneous dose of CT-P47 or EU-tocilizumab. The primary endpoint (Part 2) was PK equivalence by area under the concentration - time curve (AUC) from time zero to last quantifiable concentration (AUC 0-last ), AUC from time zero to infinity (AUC 0-inf ), and maximum serum concentration (C max ). PK equivalence was concluded if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the 80-125% equivalence margin. Additional PK endpoints, immunogenicity, and safety were evaluated., Results: In Part 2, 289 participants were randomized (146 CT-P47; 143 EU-tocilizumab); 284 received study drug. AUC 0-last , AUC 0-inf , and C max were equivalent between CT-P47 and EU-tocilizumab: 90% CIs for the ratios of gLSMs were within the 80-125% equivalence margin. Secondary PK endpoints, immunogenicity, and safety were comparable between groups., Conclusions: CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults., Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT05188378.

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies.

Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.

Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-Cre ERT2 ; PKM2 f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

Glutathione (GSH) is necessary for maintaining physiological antioxidant function, which is responsible for maintaining free radicals derived from reactive oxygen species at low levels and is associated with improved cognitive performance after brain injury. GSH is produced by the linkage of tripeptides that consist of glutamic acid, cysteine, and glycine. The adequate supplementation of GSH has neuroprotective effects in several brain injuries such as cerebral ischemia, hypoglycemia, and traumatic brain injury. Brain injuries produce an excess of reactive oxygen species through complex biochemical cascades, which exacerbates primary neuronal damage. GSH concentrations are known to be closely correlated with the activities of certain genes such as excitatory amino acid carrier 1 (EAAC1), glutamate transporter-associated protein 3-18 (Gtrap3-18), and zinc transporter 3 (ZnT3). Following brain-injury-induced oxidative stress, EAAC1 function is negatively impacted, which then reduces cysteine absorption and impairs neuronal GSH synthesis. In these circumstances, vesicular zinc is also released into the synaptic cleft and then translocated into postsynaptic neurons. The excessive influx of zinc inhibits glutathione reductase, which inhibits GSH's antioxidant functions in neurons, resulting in neuronal damage and ultimately in the impairment of cognitive function. Therefore, in this review, we explore the overall relationship between zinc and GSH in terms of oxidative stress and neuronal cell death. Furthermore, we seek to understand how the modulation of zinc can rescue brain-insult-induced neuronal death after ischemia, hypoglycemia, and traumatic brain injury.

P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1 , and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects. The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined. Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean C max , AUC inf , and AUC 0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL ( p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL ( p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL ( p = 0.2678), respectively. In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects., Competing Interests: Conflict of Interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare, (Copyright © 2022 Translational and Clinical Pharmacology.)

Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells. Under normal conditions, ceramide plays an important role in various physiological functions, such as differentiation and apoptosis. However, under pathological conditions, excessive ceramide production is toxic and activates the neuronal-death pathway. Therefore, we hypothesized that the inhibition of ASMase activity by imipramine would reduce ceramide formation and thus prevent TBI-induced neuronal death. To test our hypothesis, an ASMase inhibitor, imipramine (10 mg/kg, i.p.), was administrated to rats immediately after TBI. Based on the results of this study, we confirmed that imipramine significantly reduced ceramide formation, dendritic loss, oxidative stress, and neuronal death in the TBI-imipramine group compared with the TBI-vehicle group. Additionally, we validated that imipramine prevented TBI-induced cognitive dysfunction and the modified neurological severity score. Consequently, we suggest that ASMase inhibition may be a promising therapeutic strategy to reduce hippocampal neuronal death after TBI.

During seizure activity, glucose and Adenosine triphosphate (ATP) levels are significantly decreased in the brain, which is a contributing factor to seizure-induced neuronal death. Dichloroacetic acid (DCA) has been shown to prevent cell death. DCA is also known to be involved in adenosine triphosphate (ATP) production by activating pyruvate dehydrogenase (PDH), a gatekeeper of glucose oxidation, as a pyruvate dehydrogenase kinase (PDK) inhibitor. To confirm these findings, in this study, rats were given a per oral (P.O.) injection of DCA (100 mg/kg) with pyruvate (50 mg/kg) once per day for 1 week starting 2 h after the onset of seizures induced by pilocarpine administration. Neuronal death and oxidative stress were assessed 1 week after seizure to determine if the combined treatment of pyruvate and DCA increased neuronal survival and reduced oxidative damage in the hippocampus. We found that the combined treatment of pyruvate and DCA showed protective effects against seizure-associated hippocampal neuronal cell death compared to the vehicle-treated group. Treatment with combined pyruvate and DCA after seizure may have a therapeutic effect by increasing the proportion of pyruvate converted to ATP. Thus, the current research demonstrates that the combined treatment of pyruvate and DCA may have therapeutic potential in seizure-induced neuronal death.

Peach gummosis disease has been identified as a serious challenge in Korean agriculture and has developed to become a major cause of agricultural productivity losses. However, treatments for gummosis have not been systemically established and studies of the microbiome closely related to this plant disease are lacking. Therefore, we analyzed the bacterial and fungal communities in the bark and rhizosphere soil of healthy peach trees and those with gummosis. Through high-throughput sequencing, we obtained unprecedented insights into the bacterial and fungal dynamics of each group, including their diversity and taxonomic classification, as well as network analyses. We found that the presence of gummosis drives a significantly higher alpha diversity in the bark bacterial community. Peach gummosis bark mycobiomes included greater numbers of opportunistic pathogens such as Ascochyta , Botryosphaeria , Saccharomyces , Nectriaceae&#95;NA , Trametes , and Valsaceae&#95;NA. However, the microbiome also included bacteria beneficial to plant growth and the production of polysaccharides-namely, 1174-901-12 , Catenibacterium , Cutibacterium , Friedmanniella , Methylobacterium-Methylorubrum , Pseudomonas , Rhodobacter , and Sphingomonas . Furthermore, we confirmed that gummosis induced a more complex structure in the bark microbiome network. We conclude that the findings of this study provide a valuable aid in profiling the overall peach tree microbial ecosystem, which can be utilized to develop precise biomarkers for the early diagnosis of gummosis.

Organochlorine pesticides in soil samples across urban, suburban, agricultural, and industrial sites were analyzed every year between 2013 and 2016 in South Korea. The study aims to understand the residual status, diminution of occurrence from the South Korean environment, and its risk to humans after three decades of the ban. A general decreasing trend of OCPs has been observed over the years. The OCP concentrations were below the guideline values prescribed for soil pollution. Metabolites like p,p'-DDD and endosulfan sulfate contributed a major portion to the total OCP concentration over the years. The agricultural sites showed higher OCP levels than other site types. Compositional profile and diagnostic ratios suggested that the occurrence of DDT and endosulfan residues were due to historical inputs, but those of HCH and chlordane reflect recent usage in some pockets. The calculated incremental lifetime cancer risk was within the safety limit for all age groups across the genders in the majority of the sites. It is evident that the OCP load on soil is decreasing since the ban on usage. However, regular monitoring with a special focus on metabolites can be an effective control measure to regulate and eliminate the contamination of OCPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Owing to the emergence and improvement of high-throughput technology and the associated reduction in costs, next-generation sequencing (NGS) technology has made large-scale sampling and sequencing possible. With the large volume of data produced, the processing and downstream analysis of data are important for ensuring meaningful results and interpretation. Problems in data analysis may be encountered if researchers have little experience in using programming languages, especially if they are clinicians and beginners in the field. A strategy for solving this problem involves ensuring easy access to commercial software and tools. Here, we observed the current status of free web-based tools for microbiome analysis that can help users analyze and handle microbiome data effortlessly. We limited our search to freely available web-based tools and identified MicrobiomeAnalyst, Mian, gcMeta, VAMPS, and Microbiome Toolbox. We also highlighted the various analyses that each web tool offers, how users can analyze their data using each web tool, and noted some of their limitations. From the abovementioned list, gcMeta, VAMPS, and Microbiome Toolbox had several issues that made the analysis more difficult. Over time, as more data are generated and accessed, more users will analyze microbiome data. Thus, the availability of free and easily accessible web tools can enable the easy use and analysis of microbiome data, especially for those users with less experience in using command-line interfaces.

Organochlorine pesticides (OCPs) are widely used in certain countries. We determined atmospheric concentrations, distribution patterns, and seasonal variations of OCPs at four sites in South Korea for 1 year. Samples of 22 OCPs were collected using a high-volume air sampler, and measured via the isotope dilution method with HRGC/HRMS. In South Korea, pentachlorobenzene (PeCB), hexachlorocyclohexane (HCB), and endosulfan (EnSF) were dominant, accounting for > 87% of total OCPs. Spatial distributions showed significant differences and the highest levels were observed in Seosan (295.2 pg·m -3 ), indicating the compounding potential of diverse sources as Seosan has concentrated large-scale industrial complexes and agricultural activity (Seoul: 243.6 pg·m -3  > Jeju: 193.5 pg·m -3  > Baengnyeong: 178.2 pg·m -3 ). The isomeric ratios of OCPs in the South Korean atmosphere indicated that the dominant sources of HCB and dichlorodiphenyltrichloroethane were primarily used in the past; meanwhile, chlordane (CHL) and EnSFs were derived from recent material inputs. Seasonally, OCP concentrations largely peaked in summer with minimum values in winter. This apparent temperature dependence suggests the re-volatilization of accumulated chemicals into the atmosphere. Additionally, an air mass back trajectory indicated the influence of pollutants released from a reservoir through long-range atmospheric transport in the summer. In particular, restricted OCPs are primarily released into the atmosphere by inadvertent sources, such as industrial activities and volatilization from contaminated areas. Thus, severe OCP pollution in Korea is due to the mobile nature of the particles. These data can be useful for the continuous monitoring of long-range transported air pollutants that are transferred between countries., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Stroke-related sarcopenia is caused by various factors, such as brain damage, systemic catabolic state, skeletal muscle imbalance, and malnutrition. In the long-term care plan after stroke, appropriate rehabilitation strategies to achieve maximum functional improvement and prevent the development of sarcopenia are important. This study has investigated the effect of branched-chain amino acid (BCAA) supplementation on sarcopenia after stroke. We also evaluated the effect of BCAA on functional improvement during the intensive rehabilitation period., Methods: Patients with subacute stroke with stroke-related disabilities were enrolled and given dietary supplement powder containing BCAAs for 1 month. These BCAAs were supplied through the nutrition team during feeding time. Patients whose age, sex, and stroke lesions were similar to those of the study group were enrolled in the control group through medical record review. Both groups received personalized intensive inpatient rehabilitation therapy in a single-unit rehabilitation center. All patients' target calories were calculated regularly by the nutritional support team in our institution. Sarcopenia status was evaluated using grip strength and the skeletal muscle index (SMI), which was assessed by dual-energy X-ray absorptiometry (DEXA). The functional status associated with stroke was evaluated every month, including activities of daily living, balance, gait, and swallowing., Results: A total of 54 patients were enrolled, with 27 patients in each of the two groups. The study group showed significantly greater improvement in SMI after intervention than the control group. Both groups improved functionally over time, but the improvement in the study group was significantly greater than that in the control group. Univariate analysis revealed that patients with better functional status had a greater SMI with a combination of BCAA supplementation and intensive rehabilitation therapy., Conclusion: Our results showed a positive effect of BCAA supplementation on sarcopenia after stroke. We also found that nutritional support helps functional improvement during neurological recovery. These results suggest that comprehensive rehabilitation intervention combined with BCAA supplementation could be a helpful option during the critical period of post-stroke neurological recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Lee, Choi, Lee and Lee.)

Following the reduction of incinerator emission, enacted by the Korean Government in 2001, the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the air (-96%) have significantly decreased. However, their levels in the human serum of the general Korean population have not reduced at the same rate (-36%), indicating that humans may also be unintentionally exposed to these compounds, primarily through food ingestion. In this study, the risk of dietary exposure was assessed on a large scale, to provide toxicological information and guide the development of food safety policies. The food consumption data of the extreme (95th percentile) group and various subgroups (by age, pregnancy, and lactation), as well as the average group, were utilized. Compared to the tolerable daily intake (TDI) established by the World Health Organization (WHO), the average daily dietary exposure of the general Korean population, calculated using a deterministic method, was 11.9% of the WHO TDI (4 pg-TEQ WHO05 kg body weight -1 d -1 ). For additional comparison, a probabilistic method using a Monte Carlo simulation was applied to the same data. Finally, the associated potential health risk was quantitatively characterized, and the results suggest the importance of non-dioxin-like congeners in future risk assessments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Per the well-known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment-naïve and lamivudine-resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open-label, single-dose parallel-group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration-time curves of LB80331 increased by 1.5-, 2.5-, and 4.5-fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8-, 3.2-, and 6.2-fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment., (© 2021, The American College of Clinical Pharmacology.)

Evaluation for the controlling policy's effectiveness to mitigate criteria air pollutants (CAPs) in South Korea during December 1, 2019-March 31, 2020 is difficult because of its coincidence with the COVID-19 social distancing. In this study, we differentiated the influence of three major driving factors (intensive controlling policy by the government, meteorological conditions, and social distancing) to the CAP variation in Ulsan, the largest industrial city in South Korea. In 2013-2019, the concentrations of PM 2.5 (2015-2019), PM 10 , SO 2 , and NO 2 decreased by 6.7, 1.6, 4.2, and 3.3%/year, respectively, whereas the O 3 concentration slightly increased by 0.7%/year. Trend analysis was used to predict the CAP concentrations before (January 1-February 21) and during (February 22-March 31) the social distancing in 2020. The difference between the measured and predicted concentrations was designated as the contribution of the three factors. The controlling policy was the most important driver of the CAP reductions. In particular, its contributions were 94.1% (January 1-February 21) and 87.4% (February 22-March 31) to the PM 2.5 decrease. The change in meteorological conditions considerably affected the CAP reductions, with the highest contributions of 35.2% (January 1-February 21) and 39.2% (February 22-March 31) to the O 3 decrease. On February 22-March 31, the effects of social distancing were 1.6, 0.6, 1.3, and 1.4% to the reduction of SO 2 , NO 2 , PM 10 , and PM 2.5 , respectively. Overall, a decrease in the CAP concentrations was apparent during January-March 2020 in Ulsan primarily due to the intensive controlling policies, not by the COVID-19 social distancing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aims to investigate the spatial distribution of and temporal variation in the phase distribution, emission sources, and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in runoff and in surface water mixed with runoff discharge. The samples were collected at semi-rural, residential, and industrial sites in Ulsan, South Korea, from April to October 2016. The industrial site had the highest PAH concentrations in the runoff and surface water due to the higher PAH levels found in the surrounding environmental media. The PAH phase distributions were relatively similar between the sampling sites, with dissolved PAHs (2- to 4-ring species) dominant. In July, the PAHs in the surface water were more commonly found in the dissolved phase due to the higher water temperature and dissolved organic carbon concentration. The emission sources for the PAHs were identified using principal component analysis (PCA), a dimension reduction technique, and the k-nearest neighbor (KNN) classifier, a supervised learning algorithm. It was determined that the PAHs in the runoff and surface water were likely to share similar petrogenic and pyrolysis sources for most of the sampling periods. The ecological risk of the surface water was 1.5-4.5 times lower after being mixed with runoff water, mainly due to dilution effects. The ecological risk for surface water was highest in July because of the higher PAH concentrations. This study contributes to the understanding of PAHs in runoff and in surface water affected by runoff discharge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Toxic metals, As, and As species were monitored at 18 stations along the Taehwa River in Ulsan. The concentrations of Ni (98.4 μg/L) at stations near industrial areas were relatively high and exceeded the WHO's drinking water guidelines (70 μg/L) and the US EPA's national recommended water quality criteria (52 μg/L). Principal component analysis and cluster analysis revealed that Ni and Cu were more strongly influenced by industrial activity than other elements in the Taehwa River estuary. Analysis of the hazard quotient (HQ) and cancer risk (CR) indicated that As was of the greatest non-carcinogenic and carcinogenic concern. Notably, the HQ and CR of As III at suburban stations exceeded 1 and 10 -4 , respectively, representing a significant health risk. These results indicate that As speciation testing is crucial for the development of effective management plans based on health risks because the toxicity and mobility of As depend on its chemical form., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC 0-inf ); AUC from time zero to the last quantifiable concentration (AUC 0-last ); and maximum serum concentration (C max ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC 0-inf , AUC 0-last , and C max were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars., (© 2021 Celltrion, Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

This study investigates the contamination characteristics of polychlorinated naphthalenes (PCNs) in the rice paddy soils of two industrial cities (Pohang and Ulsan) in South Korea. The paddy soils were collected from 40 sites in the paddy fields near industrial complexes in both cities. The mean concentration of Σ 55 PCNs was 145.9 ± 101.7 pg/g and 95.4 ± 41.4 pg/g for the soils in Pohang and Ulsan, respectively. The toxic equivalents (TEQs) of Σ 28 PCNs ranged from 0.007 pg-TEQ/g to 0.069 pg-TEQ/g in Pohang, and 0.015 pg-TEQ/g to 0.046 pg-TEQ/g in Ulsan. The PCN profiles were dominated by lower chlorinated homologues such as tetra- and tri-CNs for both cities, which are associated with the historical use of technical products, or more specifically, Halowaxes (HW 1099, 1031, 1013, and 1001). The results of the principal component analysis (PCA) indicate that the historical residues from the technical products contributed to the PCN contamination, but the influence of combustion sources was also observed with a high fraction of combustion-related congeners. Based on this study, we can expect that rice grown in these paddy fields will accumulate PCNs and other combustion-related pollutants, strongly suggesting the necessity for multimedia (e.g., air, soil, water, and rice) monitoring and human exposure assessments of PCNs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Varenicline is an efficacious aid for smoking cessation. In this study, the pharmacokinetics and safety were compared between film-coated tablets of varenicline tartrate (reference drug) and the newly developed orally disintegrating films of varenicline salicylate (test drug), both of them contained 1 mg of varenicline., Materials and Methods: A randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted in healthy male subjects. Serial blood samples were obtained for up to 72 hours in each period, with a washout period of 7 days or more. The pharmacokinetic parameters were calculated using the noncompartmental method. Safety profiles were assessed throughout the study., Results: A total of 28 subjects completed the study. The plasma varenicline concentration-time profiles were similar for the two study drugs. The maximum plasma varenicline concentration (C max ) was 5,768.95 ng/L (mean) and 5,780.55 ng/L for the test drug and reference drug, respectively. The areas under the concentration-time curve from time 0 to the last measurable time point (AUC 0-t ) were 94,086.30 h×ng/L and 89,958.55 h×ng/L for the test drug and reference drug, respectively. The geometric mean ratios (90% confidence intervals) of the test drug to the reference drug for C max and AUC 0-t were 0.9955 (0.9488 - 1.0444) and 1.0449 (0.9848 - 1.1088), respectively, which fell within the bioequivalence range of 0.8 - 1.25. There was no difference in safety between the study drugs., Conclusion: The pharmacokinetics and safety profiles were similar between the two study drugs. The orally disintegrating film of varenicline salicylate can be an alternative to varenicline tartrate tablets.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66-3.61 in the 1 H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (K p ) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (C max ) and area under the plasma concentration-time curve from 0 h to the last time point (AUC t ) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Purpose: Combination therapy with insulin-independent sodium-glucose cotransporter 2 inhibitors and thiazolidinedione drugs, such as lobeglitazone, has been reported to elicit potential additive efficacy in glycemic control in type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetic (PK) drug-drug interactions between empagliflozin and lobeglitazone in healthy subjects., Subjects and Methods: A randomized, open-label, multiple-dose study was conducted in 30 healthy subjects using a three-treatment, six-sequence, three-way crossover design. Subjects received one of the following treatments once daily for 5 days in each period: 25 mg empagliflozin, 0.5 mg lobeglitazone sulfate, or a combination. Serial blood sampling before every dose and up to 24 h after the last dose was performed during each treatment period. The PK parameters were estimated using noncompartmental methods with the plasma empagliflozin and lobeglitazone concentrations. The absence of a PK interaction was construed as the 90% confidence interval (90% CI) of maximum concentration at steady state (C max,ss ) and area under the concentration-time curve over the dosing interval (AUC tau ) for combination therapy-to-monotherapy ratios within the limits of 0.80-1.25., Results: The steady-state plasma empagliflozin and lobeglitazone concentration-time profiles of combination therapy and monotherapy were comparable in the 25 subjects who completed the study. Coadministration of empagliflozin with lobeglitazone did not affect empagliflozin PK (with 90% CIs of 0.956-1.150 and 0.945-1.133 for C max,ss and AUC tau , respectively). Likewise, empagliflozin did not affect lobeglitazone C max,ss or AUC tau (with 90% CIs of 0.869-0.995 and 0.851-1.018, respectively). All treatment groups tolerated mild adverse events well., Conclusion: The lack of PK interactions between lobeglitazone and empagliflozin in combination therapy, along with their good tolerability, indicates that the two drugs can be coadministered without dose adjustment., Trial Registration Number: NCT02854748, Registered on August 7, 2016., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Kim et al.)

When the aspect ratio of a high aspect ratio (HAR) etching process is greatly increased, an amorphous carbon layer (ACL) hard mask is required for dynamic random-access memory (DRAM). To improve the durability of an etch hard mask, an understanding of the plasma deposition mechanisms and the deposited film properties associated with the plasma conditions and atomic structure, respectively, is required. We performed a series of plasma depositions, material characterizations and dry-etching to investigate the effect of the deposition process condition on the surface characteristics of an ACL film to be used as a dry etch hard mask in an HAR etch process. We found that a lower chamber pressure at a higher temperature for the plasma deposition process yielded higher film hardness, and this infers that higher plasma ion energy in lower pressure regions helps to remove hydrogen atoms from the surface by increased ion bombardment. It was postulated that a higher substrate temperature gears the bake-out of hydrogen or hydroxide contaminants. From the results of inductively coupled plasma-reactive ion etching of the deposited ACL film, we observed that the etch selectivity over the silicon dioxide film was improved as C═C sp ₂ and C-C sp ₃ bonds increased.

The miniaturization of devices requires the introduction of a high aspect ratio through patterning in the Damascene copper interconnect process. The high aspect ratio etch process employs hardmasks, such as amorphous carbon, that can withstand high-powered plasma exposure. When an etch hardmask is removed after patterning, the properties of the underlying film can be altered by the effect of plasma exposure during the strip process. In this study, surface properties of SiOC(H) are investigated after an amorphous carbon strip with O 2 /Ar plasma. Since the low-k film of SiOC(H) structure shows characteristics according to the Si-O internal bonding structure, the Si-O bonding ratio of the ring, network and cage structure was analyzed through Fourier-transform infrared (FT-IR) analysis to measure changes in thin film properties. X-ray photoelectron spectroscopy (XPS) was also used to add reliability to the SiOC(H) film structure. In addition, the end point of the strip process was obtained using an optical emission spectroscopy sensor and variations in thin film characteristics over the plasma exposure time were analyzed. These results revealed the structural modification of the SiCO(H) thin film in the post-etch strip of the amorphous carbon layer (ACL) hardmask.

The outbreak of COVID-19 in Daegu, South Korea, early in 2020 has led this metropolitan city to become one of the major hotspots in the world. This study investigates the association of meteorology and the new daily COVID-19 confirmed cases and the effects of the city lockdown on the variation in criteria air pollutants (CAPs) in Daegu. Ambient temperature and relative humidity were negatively correlated to the new daily cases and played an important role in the spread of COVID-19. Wind speed could enhance the virus transmission through the inhalation of aerosols and/or droplets and contact with fomites. The lockdown has directly decreased the concentrations of CAPs. In particular, reductions of 3.75% (PM 10 ), 30.9% (PM 2.5 ), 36.7% (NO 2 ), 43.7% (CO), and 21.3% (SO 2 ) between the period before and during the outbreak were observed over the entire city. An increase in O 3 (71.1%) was affected by natural processes and photochemical formation other than the lockdown effects. The three central districts were the areas most affected by the virus and showed the highest reductions in CAPs (except for O 3 ) during the outbreak. Apart from the influence of the lockdown, the decreasing trend in CAPs may be a result of the actions taken by the government to mitigate air pollutants nationwide since 2019. The results of this study can be useful for government and medical organizations to understand the behavior of the virus in the atmosphere. Further studies are necessary to explore the detailed influences of the lockdown on the environment and public life.

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.

River and coastal sediments were collected at 17 stations in Ulsan, the largest industrial city in South Korea, to evaluate the levels, profiles, emission sources, and spatial distribution of polycyclic aromatic hydrocarbons (PAHs). The mean concentration of Σ 16 PAHs was 722 ng/g, and fluoranthene was a predominant compound. PAHs with 4-6 rings showed higher proportions than PAHs with 2-3 rings. The stations located near industrial complexes showed elevated levels of indicator compounds for petroleum, coal, coke, and fuel combustion. Therefore, petrochemical industries, coal pier, non-ferrous industries, and vehicles were identified as the emission sources. As industrialization and urbanization progressed, an increase in PAH levels and profile changes were observed as a result of the increasing industrial fuel consumption and the increasing number of vehicles. This is the first study that confirmed the change of PAHs in sediment caused by the change of emission sources over time in Ulsan., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood-brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.

Epilepsy is one of the most common and severe brain diseases. The exact cause of epilepsy is unclear. Epilepsy often occurs following brain damage, such as traumatic brain injury (TBI) and ischemia. Cerebrolysin is a porcine brain peptide that is a unique neurotropic and neuroprotective agent. Cerebrolysin has been reported to increase neuroprotective effects after TBI, ischemia, and other CNS diseases. However, the effects of cerebrolysin on seizures are not known. Therefore, this study aimed to investigate the effects of neuropeptide cerebrolysin on neuronal death in the hippocampus after a seizure. To confirm the effects of cerebrolysin, we used a pilocarpine-induced seizure animal model. Cerebrolysin (2.5 ml/kg, i.p., once per day for 7 days) was immediately injected after a seizure induction. After 1 week, we obtained brain tissues and performed staining to histologically evaluate the potentially protective effects of cerebrolysin on seizure-induced neuronal death in the hippocampus. We found that cerebrolysin decreased hippocampal neuronal death after a seizure. In addition, an increase in brain-derived neurotrophic factor (BDNF) was confirmed through Western blot analysis to further support our hypothesis. Therefore, the present study suggests that the administration of cerebrolysin can be a useful therapeutic tool for preventing neuronal death after a seizure., (Copyright © 2020 Kang, Choi, Lee, Kho, Jeong, Hong, Kang, Park, Song, Choi, Lim and Suh.)

A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage. Several previous studies have shown that TRPM2 channel activation contributes to neuroinflammation and neurodegeneration cascades. Therefore, we examined whether anti-oxidant treatment, such as with N -acetyl-l-cysteine (NAC), provides neuroprotection via regulation of TRPM2, following global cerebral ischemia (GCI). Experimental animals were then immediately injected with NAC (150 mg/kg/day) for 3 and 7 days, before sacrifice. We demonstrated that NAC administration reduced activation of GCI-induced neuronal death cascades, such as lipid peroxidation, microglia and astroglia activation, free zinc accumulation, and TRPM2 over-activation. Therefore, modulation of the TRPM2 channel can be a potential therapeutic target to prevent ischemia-induced neuronal death.

We investigate the characteristics of short-term and long-term synaptic plasticity in a Si-based fieldeffect transistor (FET)-type memory device. An Al₂O₃/HfO₂/Si₃N₄/SiO₂ gate dielectric stack is used to realize short-term and long-term plasticity (STP/LTP). Si₃N₄ and HfO₂ layers are designed to charge trap layer for synaptic device. The mechanism of STP and LTP operation is analyzed by considering the device response to the potentiation and depression pulses and retention measurement of the memory functionality. To investigate the STP operation, paired pulse facilitation (PPF) measurement is performed. The retention characteristic is also studied to validate the LTP property of the device. By investigating a device with an Al₂O₃/HfO₂/Si₃N₄ stack as a control device, it is shown that the Al₂O₃/HfO₂/Si₃N₄/SiO₂ stack device is suitable for a synaptic device in neuromorphic systems.