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This paper proposes a heuristic association algorithm between access points (APs) and user equipment (UE) in user-centric cell-free massive multiple-input-multiple-output (MIMO) systems, specifically targeting scenarios where UEs share the same frequency and time resources. The proposed algorithm prevents overserving APs and ensures the connectivity of all UEs, even when the number of UEs is significantly greater than the number of APs. Additionally, we assume the use of low-resolution analog-to-digital converters (ADCs) to reduce fronthaul capacity. While realistic massive access scenarios, such as those in Internet-of-Things (IoT) environments, often involve hundreds or thousands of UEs per AP using multiple access techniques to allocate different frequency and time resources, our study focuses on scenarios where UEs within each AP cluster share the same frequency and time resources to highlight the impact of pilot contamination in dense network environments. The proposed algorithm is validated through simulations, confirming that it guarantees the connection of all UEs and prevents overserving APs. Furthermore, we analyze the required fronthaul capacity based on quantization bits and confirm that the proposed algorithm outperforms existing algorithms in terms of SE and average SE performance for UEs.

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials., Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects., Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%., Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life.

We aimed to assess the temporal trends of incident syphilis and its associated risk factors among men with HIV (Human Immunodeficiency Virus) in Korea during the COVID-19 pandemic. We conducted a retrospective cohort study of men with HIV attending an HIV clinic in Korea between 2005 and 2022. Of 767 men with HIV, 499 were included and contributed 3220 person-years (PY) of the observation period. Eighty-two patients were diagnosed with incident syphilis, with an overall incidence of 2.55/100 PY (95% confidence interval [CI] 20.56-31.53). The incidence of syphilis per 100 PY gradually decreased from 2.43 (0.79-7.42) in 2005-2007 to 1.85 (1.08-3.17) in 2014-2016; however, it increased to 3.0 (1.99-4.53) in 2017-2019, and further to 3.33 (2.26-4.89) in 2020-2022. A multivariate analysis identified young age (≤30 years versus >50, adjusted HR 6.27, 95% CI 2.38-16.56, p < 0.001), treponemal test positive at baseline (2.33, 1.48-3.67, p < 0.001), men who have sex with men (2.36, 1.34-4.16, p = 0.003), and history of incarceration (2.62, 1.21-5.67, p = 0.015) as risk factors for incident syphilis. Recently, syphilis incidence in men with HIV has increased in Korea, especially in young patients and at-risk groups, highlighting the need for enhanced regular screening and targeted behavioral interventions among these populations.

Fluorosilicone rubber, essential in automotive and aerospace owing to its excellent chemical resistance, plays a pivotal role in sealing technology, addressing the industry's evolving demands. This study explores the preparation and properties of fibrillated cellulose-reinforced fluorosilicone rubber composites to enhance their stiffness and oil resistance. Fibrillated cellulose sourced as a wet cake and subjected to processing and modification is incorporated into a fluorosilicone rubber matrix. The resulting composites are analysed by tensile and compression tests, along with compressive stress-relaxation testing in air and in an oil-immersed environment. The findings demonstrate significant improvements in the mechanical properties, including an increased Young's modulus and elongation at break, whereas the tensile strength remained uncompromised throughout the testing procedures. Morphological analysis of the fracture surfaces revealed a remarkable interfacial affinity between the fibrillated cellulose and rubber matrix, which was attributed in part to the modified fatty acids and inorganic nanoparticles. The presence of fibrillated cellulose enhanced the stress-relaxation characteristics under oil-immersion conditions. These results contribute to the domain of advanced elastomer materials, with potential for applications requiring enhanced mechanical properties and superior oil resistance.

Developing new organic solvents to support the use of Li metal anodes in secondary batteries is an area of great interest. In particular, research is actively underway to improve battery performance by introducing fluorine to ether solvents, as these are highly compatible with Li metal anodes because fluorine imparts high oxidative stability and relatively low Li-ion solvation ability. However, theoretical analysis of the solvation ability of organic solvents mostly focuses on the electron-withdrawing capability of fluorine. Herein, we analyze the effect of the structural characteristics of solvents on their Li + ion solvation ability from a computational chemistry perspective. We reveal that the structural constraints imposed on the oxygen binding sites in solvent molecules vary depending on the structural characteristics of the N-membered ring formed by the interaction between the organic solvent and Li + ions and the internal ring containing the oxygen binding sites. We demonstrate that the structural strain of the organic solvents has a comparable effect on Li + solvation ability seen for the electrical properties of fluorine elements. This work emphasizes the importance of understanding the structural characteristics and strain when attempting to understand the interactions between solvents and metal cations and effectively control the solvation ability of solvents.

Emerging evidence indicates that intracellular calcium (Ca 2+ ) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca 2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

The reconfigurable intelligent surface (RIS) and rate-splitting multiple access (RSMA) are considered as promising technologies for the beyond Fifth-Generation (B5G) and Sixth-Generation (6G) wireless systems by controlling the propagation environment, which attenuates the transmitted signal, and by managing the interference by splitting the user message into common and private messages. Because conventional RIS elements have each impedance connected to the ground, the sum-rate performance improvement of the RIS is limited. Therefore, the new RISs, which have impedance elements connected to each other, have been proposed recently. To be more adaptive to each channel, the optimization of the grouping of the RIS elements is required. Furthermore, since the solution of the optimal rate-splitting (RS) power-splitting ratio is complex, the value should be simply optimized to be more practical in the wireless system. In this paper, the grouping scheme of the RIS elements according to the user scheduling and the solution of the RS power-splitting ratio based on fractional programming (FP) are proposed. The simulation results showed that the proposed RIS-assisted RSMA system achieved a high sum-rate performance compared to the conventional RIS-assisted spatial-division multiple access (SDMA) system. Therefore, the proposed scheme can perform adaptively for the channel and has a flexible interference management. Furthermore, it can be a more suitable technique for B5G and 6G.

Tegoprazan is a novel potassium-competitive acid blocker. This study investigated the effect of drug-drug interaction on the pharmacokinetics and pharmacodynamics of tegoprazan co-administered with amoxicillin and clarithromycin, the first-line therapy for the eradication of Helicobacter pylori , using physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling. The previously reported tegoprazan PBPK/PD model was modified and applied. The clarithromycin PBPK model was developed based on the model provided by the SimCYP ® compound library. The amoxicillin model was constructed using the middle-out approach. All of the observed concentration-time profiles were covered well by the predicted profiles with the 5th and 95th percentiles. The mean ratios of predicted to observed PK parameters, including the area under the curve (AUC), maximum plasma drug concentration (C max ), and clearance, were within the 30% intervals for the developed models. Two-fold ratios of predicted fold-changes of C max and AUC from time 0 to 24 h to observed data were satisfied. The predicted PD endpoints, including median intragastric pH and percentage holding rate at pH above 4 or 6 on day 1 and day 7, were close to the corresponding observed data. This investigation allows evaluation of the effects of CYP3A4 perpetrators on tegoprazan PK and PD changes, thus providing clinicians with the rationale for co-administration dosing adjustment.

Patellofemoral pain syndrome (PFPS) is a common cause of anterior knee pain, and therapeutic exercises are recommended. During the COVID-19 pandemic, despite recommendations on the importance of telerehabilitation, insufficient studies have investigated functional outcomes between supervised rehabilitation and telerehabilitation in patients with PFPS. This study aimed to compare the muscle strength, muscle activation time, and patient-reported outcomes between supervised rehabilitation and telerehabilitation in female patients with PFPS. A total of 61 patients (supervised, n = 30; telerehabilitation, n = 31) participated. Muscle strength and activation time of the quadriceps and hamstrings were measured using an isokinetic device. Hip muscle strength was evaluated using a hand-held dynamometer. Patient-reported outcomes were measured using the visual analog scale (VAS) for pain, Kujala Anterior Knee Pain Scale (AKPS) for functional ability, and Tampa scale for kinesiophobia (TSK-11). No significant differences were found in muscle strength, muscle activation time, or patient-reported outcomes of the involved knees between the two groups ( p > 0.05). In addition, the rate of change in all parameters did not significantly differ between the two groups ( p > 0.05). Telerehabilitation, such as a home-exercise program supervised by physical therapists, may be as effective as supervised rehabilitation in improving functional outcomes in female patients with PFPS.

Abnormal foot posture and poor muscle performance are potential causes of plantar fasciitis (PF). However, no study has compared the differences between lower extremity muscle performance and foot pressure in patients who have PF with and without abnormal foot postures. This study aimed to compare the differences in lower extremity muscle performance, such as in the hip, quadriceps, hamstring, and plantar flexor, and foot pressure in patients who have PF with and without flat foot postures. Seventy patients with plantar heel pain were enrolled (37 flat feet and 33 without flat feet). The hip muscle strength was measured using a handheld digital dynamometer. The strength and reaction time of the quadriceps, hamstring, and plantar flexor muscles were evaluated using an isokinetic device. Foot pressure parameters were assessed using pedobarography. The strength of the plantar flexor muscles was significantly lower ( p = 0.008), while the reaction time of the plantar flexor muscles was significantly faster ( p = 0.007) for the involved feet of PF patients with flat feet than in those without flat feet. This study confirmed the differences in muscle performance between patients who have PF with different foot postures. Therefore, clinicians and therapists should plan treatment considering the differences in these characteristics for the management of these patients.

To broaden the range of measurable pesticides for stable isotope analysis (SIA), we tested whether SIA of the anthranilic diamides cyantraniliprole (CYN) and chlorantraniliprole (CHL) can be achieved under elemental analyzer/isotope ratio mass spectrometry with compound purification in high-performance liquid chromatography (HPLC). Using this method, carbon isotope compositions were measured in pesticide residues extracted from plants (lettuce) grown indoors in potting soil that were treated with 500 mg/kg CHL and 250 mg/kg CYN and were followed up for 45 days. Our results show that the CYN and CHL standard materials did not have significant isotope differences before and after clean-up processing in HPLC. Further, when applied to the CYN product and CHL product in soil, stable isotope differences between the soil and plant were observed at <1.0‱ throughout the incubation period. There was a slight increase in the variability of pesticide isotope ratio detected with longer-term incubation (CHL, on average 1.5‱). Overall, we measured the carbon isotope ratio of target pesticides from HPLC fraction as the purification and pre-concentration step for environmental and biological samples. Such negligible isotopic differences in pesticide residues in soils and plants 45 days after application confirmed the potential of CSIA to quantify pesticide behavior in environments.

Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. Therefore, we evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We enrolled 1047 patients with ovarian tumors. The predictive values and concordance rates between the preoperative risk of ovarian malignancy algorithm (ROMA) and imaging, including CT and MRI, were evaluated. Diagnoses of 561 CT (77.9%) and 322 MRI group (69.2%) participants were consistent with the ROMA. Among them, 96.4% of the CT (541/561) and 92.5% of the MRI (298/322) group predicted an accurate diagnosis. In contrast, 67.3% (101/150) of CT and 75.2% (100/133) of MRI cases accurately predicted the diagnosis in cases with discrepancies between ROMA and CT or MRI; a total of 32% (48/150) of the CT and 25.5% (34/133) of the MRI group showed an accurate ROMA diagnosis in cases with discrepancies between ROMA and imaging. In the event of a discrepancy between ROMA and imaging when ovarian tumor malignancy prediction, the question is which method should take precedence. This study demonstrates that MRI has the greatest diagnostic accuracy, followed by CT and ROMA. It is also important to understand underlying diseases and benign conditions and rare histopathologies of malignant tumors.

The market demand for marine-based cosmetics has shown a tremendous growth rate in the last decade. Marine resources represent a promising source of novel bioactive compounds for new cosmetic ingredient development. However, concern about sustainability also becomes an issue that should be considered in developing cosmetic ingredients. The fisheries industry (e.g., fishing, farming, and processing) generates large amounts of leftovers containing valuable substances, which are potent sources of cosmeceutical ingredients. Several bioactive substances could be extracted from the marine by-product that can be utilized as a potent ingredient to develop cosmetics products. Those bioactive substances (e.g., collagen from fish waste and chitin from crustacean waste) could be utilized as anti-photoaging, anti-wrinkle, skin barrier, and hair care products. From this perspective, this review aims to approach the potential active ingredients derived from marine by-products for cosmetics and discuss the possible activity of those active ingredients in promoting human beauty. In addition, this review also covers the prospect and challenge of using marine by-products toward the emerging concept of sustainable blue cosmetics.

Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.

A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model for tegoprazan and its major metabolite M1 was developed to predict PK and PD profiles under various scenarios. The PBPK model for tegoprazan and M1 was developed and predicted using the SimCYP ® simulator and verified using clinical study data obtained after a single administration of tegoprazan. The established PBPK/PD model was used to predict PK profiles after repeated administrations of tegoprazan, postprandial PK profiles, and intragastric pH changes. The predicted tegoprazan and M1 concentration-time profiles fit the observed profiles well. The arithmetic mean ratios (95% confidence intervals) of the predicted to observed values for the area under the curve (AUC 0-24 h ), maximum plasma drug concentration (C max ), and clearance (CL) for tegoprazan and M1 were within a 30% interval. Delayed time of maximum concentration (T max ) and decreased C max were predicted in the postprandial PK profiles compared with the fasted state. This PBPK/PD model may be used to predict PK profiles after repeated tegoprazan administrations and to predict differences in physiological factors in the gastrointestinal tract or changes in gastric acid pH after tegoprazan administration.

Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are traceable or detectable in tests for cancer diagnosis and treatment. Currently, fluorogenic chemical probes are widely used to detect cancer-associated proteins and their binding partners. These probes are also applicable in photodynamic therapy to determine drug efficacy and monitor regulating factors. In this review, we discuss the synthesis of chemical probes for different cancer types from 2016 to the present time and their application in monitoring the activity of transferases, hydrolases, deacetylases, oxidoreductases, and immune cells. Moreover, we elaborate on their potential roles in photodynamic therapy.

We investigated pigment and mycosporine-like amino acid (MAA) concentrations of phytoplankton and Northern krill ( Thysanoessa sp.) in sub-Arctic Kongsfjorden. Chlorophyll a (Chl-a) concentrations in the surface and middle-layer water were 0.44 μg L -1 (±0.17 μg L -1 ) and 0.63 μg L -1 (±0.25 μg L -1 ), respectively. Alloxanthin (Allo, a marker of cryptophytes) was observed at all stations, and its mean values for surface and middle-layer water were 0.09 μg L -1 (±0.05 μg L -1 ) and 0.05 (±0.02 μg L -1 ), respectively. The mean MAA-to-Chl-a ratios at the surface (3.31 ± 2.58 μg (μg Chl-a) -1 ) were significantly higher than those in the middle-layer water (0.88 ± 0.49 μg (μg Chl-a) -1 ), suggesting that these compounds play an important role in reducing UV photodamage. In gut pigment levels of Northern krill, the most abundant accessory pigment was Allo (2.79 ± 0.33 μg g -1 dry weight; d.w.), as was the accumulation of Chl-a (8.29 ± 1.13 μg g -1 d.w.). The average concentration of MAAs was 1.87 mg g -1 d.w. (±0.88 mg g -1 d.w.) in krill eyes, which was higher than that in all other body parts (0.99 ± 0.41 mg g -1 d.w.), except for the gut. Thysanoessa sp. was found to contain five identified MAAs (shinorine, palythine, porphyra-334, mycosporine-glycine, and M-332) in the krill eye, whereas shinorine and porphyra-334 were only observed in the krill body, not the eyes and gut. These findings suggest that Northern krill accumulate MAAs of various compositions through the diet (mainly cryptophytes) and translocate them among their body parts as an adaptation for photoprotection and physiological demands.

In this work, we develop a Ag@Al 2 O 3 @Ag plasmonic core-shell-satellite (PCSS) to achieve highly sensitive and reproducible surface-enhanced Raman spectroscopy (SERS) detection of probe molecules. To fabricate PCSS nanostructures, we employ a simple hierarchical dewetting process of Ag films coupled with an atomic layer deposition (ALD) method for the Al 2 O 3 shell. Compared to bare Ag nanoparticles, several advantages of fabricating PCSS nanostructures are discovered, including high surface roughness, high density of nanogaps between Ag core and Ag satellites, and nanogaps between adjacent Ag satellites. Finite-difference time-domain (FDTD) simulations of the PCSS nanostructure confirm an enhancement in the electromagnetic field intensity (hotspots) in the nanogap between the Ag core and the satellite generated by the Al 2 O 3 shell, due to the strong core-satellite plasmonic coupling. The as-prepared PCSS-based SERS substrate demonstrates an enhancement factor (EF) of 1.7 × 10 7 and relative standard deviation (RSD) of ~7%, endowing our SERS platform with highly sensitive and reproducible detection of R6G molecules. We think that this method provides a simple approach for the fabrication of PCSS by a solid-state technique and a basis for developing a highly SERS-active substrate for practical applications.

Developing peptide-based drugs are very promising to address many of the lifestyle mediated diseases which are prevalent in a major portion of the global population. As an alternative to synthetic peptide-based drugs, derived peptides from natural sources have gained a greater attention in the last two decades. Aquatic organisms including plants, fish and shellfish are known as a rich reservoir of parent protein molecules which can offer novel sequences of amino acids in peptides, having unique bio-functional properties upon hydrolyzing with proteases from different sources. However, rather than exploiting fish and shellfish stocks which are already under pressure due to overexploitation, the processing discards, regarded as secondary raw material, could be a potential choice for peptide based therapeutic development strategies. In this connection, we have attempted to review the scientific reports in this area of research that deal with some of the well-established bioactive properties, such as antihypertensive, anti-oxidative, anti-coagulative, antibacterial and anticarcinogenic properties, with reference to the type of enzymes, substrate used, degree of particular bio-functionality, mechanism, and wherever possible, the active amino acid sequences in peptides. Many of the studies have been conducted on hydrolysate (crude mixture of peptides) enriched with low molecular bioactive peptides. In vitro and in vivo experiments on the potency of bioactive peptides to modulate the human physiological functions beneficially have demonstrated that these peptides can be used in the prevention and treatment of non-communicable lifestyle mediated diseases. The information synthesized under this review could serve as a point of reference to drive further research on and development of functionally active therapeutic natural peptides. Availability of such scientific information is expected to open up new zones of investigation for adding value to underutilized secondary raw materials, which in turn paves the way for sustainability in fish processing. However, there are significant challenges ahead in exploring the fish waste as a source of bioactive peptides, as it demands more studies on mechanisms and structure-function relationship understanding as well as clearance from regulatory and statutory bodies before reaching the end user in the form of supplement or therapeutics.

Unintended pesticide pollution in soil, crops, and adjacent environments has caused several issues for both pesticide users and consumers. For users, pesticides utilized should provide higher yield and lower persistence while considering both the environment and agricultural products. Most people are concerned that agricultural products expose humans to pesticides accumulating in vegetation. Thus, many countries have guidelines for assessing and managing pesticide pollution, for farming in diverse environments, as all life forms in soil are untargeted to these pesticides. The stable isotope approach has been a useful technique to find the source of organic matter in studies relating to aquatic ecology and environmental sciences since the 1980s. In this study, we discuss commonly used analytical methods using liquid and gas chromatography coupled with isotopic ratio mass spectrometry, as well as the advanced compound-specific isotope analysis (CSIA). CSIA applications are discussed for tracing organic pollutants and understanding chemical reactions (mechanisms) in natural environments. It shows great applicability for the issues on unintended pesticide pollution in several environments with the progress history of isotope application in agricultural and environmental studies. We also suggest future study directions based on the forensic applications of stable isotope analysis to trace pesticides in the environment and crops.

Fish muscle, which accounts for 15%-25% of the total protein in fish, is a desirable protein source. Their hydrolysate is in high demand nutritionally as a functional food and thus has high potential added value. The hydrolysate contains physiologically active amino acids and various essential nutrients, the contents of which depend on the source of protein, protease, hydrolysis method, hydrolysis conditions, and degree of hydrolysis. Therefore, it can be utilized for various industrial applications including use in nutraceuticals and pharmaceuticals to help improve the health of humans. This review discusses muscle protein hydrolysates generated from the muscles of various fish species, as well as their amino acid composition, and highlights their functional properties and bioactivity. In addition, the role of the amino acid profile in regulating the biological and physiological activities, nutrition, and bitter taste of hydrolysates is discussed.

Pharmacometabolomics is a useful tool to identify biomarkers that can assess and predict response after drug administration. The primary purpose of pharmacometabolomics is to better understand the mechanisms and pathways of a drug by searching endogenous metabolites that have significantly changed after drug administration. DA-9701, a prokinetic agent, consists of Pharbitis seed and Corydalis tube extract and it is known to improve the gastrointestinal motility. Although the overall mechanism of action of DA-9701 remains unclear, its active ingredients, corydaline and chlorogenic acid, act as a 5-HT3 and D2 receptor antagonist and 5-HT4 receptor agonist. To determine the significant metabolites after the administration of DA-9701, a qualitative analysis was carried out using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometer followed by a multivariate analysis. Seven candidates were selected and a statistical analysis of fold change was performed over time. Our study concluded that all the seven selected metabolites were commonly involved in lipid metabolism and purine metabolism.

The skin health benefits of seaweeds have been known since time immemorial. They are known as potential renewable sources of bioactive metabolites that have unique structural and functional features compared to their terrestrial counterparts. In addition, to the consciousness of green, eco-friendly, and natural skincare and cosmetics products, their extracts and bioactive compounds such as fucoidan, laminarin, carrageenan, fucoxanthin, and mycosporine like amino acids (MAAs) have proven useful in the skincare and cosmetic industries. These bioactive compounds have shown potential anti-photoaging properties. Furthermore, some of these bioactive compounds have been clinically tested and currently available in the market. In this contribution, the recent studies on anti-photoaging properties of extracts and bioactive compounds derived from seaweeds were described and discussed.

Metformin is the first-line medicine for the treatment of type 2 diabetes. Drug interactions between metformin and other drugs, food, or beverages cannot only cause changes in the pharmacokinetic profiles but also affect the efficacy of metformin. The purpose of this study was to develop a rapid and reliable bioanalytical method for the detection of plasma metformin concentration in humans. To remove interfering substances in plasma, acidified acetonitrile (acetonitrile containing 0.1% formic acid) was added to samples. Ultra-high-performance liquid chromatography (UHPLC) coupled with high resolution mass spectrometry (HRMS) was used to analyze metformin and its internal standard (metformin-d6). Analyte separation was performed on a BEH HILIC analytical column (100 × 2.1 mm, 1.7 μm) using a gradient elution of 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B). The total chromatographic run time was 2 min. The developed method was validated for its linearity, accuracy and precision, selectivity (signal of interfering substance; analyte, lower limit of quantification (LLOQ) ≤ 20%; IS, IS ≤ 5%), sensitivity (LLOQ, 5 ng/mL; S/N ratio ≥ 10), stability (low quality control (LQC, 15 ng/mL), 2.95-14.19%; high quality control (HQC, 1600 ng/mL), -9.49-15.10%), dilution integrity (diluted QC (4000 ng/mL); 10-folds diluted QC (400 ng/mL); 5-folds diluted QC (800 ng/mL); accuracy, 81.30-91.98%; precision, ≤4.47%), carry-over (signal of double blank; analyte, LLOQ ≤20%; IS, IS ≤5%), and matrix effect (LQC, 10.109%; HQC, 12.271%) under various conditions. The constructed calibration curves were shown linear in the concentration range of 5-2000 ng/mL, with within- and between-run precision values of <8.19% and accuracy in the range of 91.13-105.25%. The plasma metformin concentration of 16 healthy subjects was successfully measured by applying the validated bioanalytical method.

We investigate the effect of applied gate and drain voltages on the charge transport properties in a zinc oxide (ZnO) nanowire field effect transistor (FET) through temperature- and voltage-dependent measurements. Since the FET based on nanowires is one of the fundamental building blocks in potential nanoelectronic applications, it is important to understand the transport properties relevant to the variation in electrically applied parameters for devices based on nanowires with a large surface-to-volume ratio. In this work, the threshold voltage shift due to a drain-induced barrier-lowering (DIBL) effect was observed using a Y-function method. From temperature-dependent current-voltage (I-V) analyses of the fabricated ZnO nanowire FET, it is found that space charge-limited conduction (SCLC) mechanism is dominant at low temperatures and low voltages; in particular, variable-range hopping dominates the conduction in the temperature regime from 4 to 100 K, whereas in the high-temperature regime (150-300 K), the thermal activation transport is dominant, diminishing the SCLC effect. These results are discussed and explained in terms of the exponential distribution and applied voltage-induced variation in the charge trap states at the band edge.

Tramadol is a μ-opioid receptor agonist and a monoamine reuptake inhibitor. O -desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6. A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population. Parallel artificial membrane permeation assay was performed to determine tramadol permeability, and the metabolic clearance of M1 was determined using human liver microsomes. Clinical study data were used to develop the model. Other physicochemical and pharmacokinetic parameters were obtained from the literature. Simulations for plasma concentrations of tramadol and M1 (after 100 mg tramadol was administered five times at 12-h intervals) were based on a total of 1000 virtual healthy Koreans using SimCYP ® simulator. Geometric mean ratios (90% confidence intervals) (predicted/observed) for maximum plasma concentration at steady-state (C max,ss ) and area under the curve at steady-state (AUC last,ss ) were 0.79 (0.69-0.91) and 1.04 (0.85-1.28) for tramadol, and 0.63 (0.51-0.79) and 0.67 (0.54-0.84) for M1, respectively. The predicted time-concentration profiles of tramadol fitted well to observed profiles and those of M1 showed under-prediction. The developed model could be applied to predict concentration-dependent toxicities according to CYP2D6 genotypes and also, CYP2D6-related drug interactions., Competing Interests: The authors declare no conflicts of interest.

This study evaluated the clinical significance of the lymph-node ratio (LNR) and its usefulness as an indicator of supraclavicular lymph-node radiation therapy (SCNRT) in pN1 breast cancer patients with disease-free survival (DFS) outcomes. We retrospectively analyzed the clinical data of patients with pN1 breast cancer who underwent partial mastectomy and taxane-based sequential adjuvant chemotherapy with postoperative radiation therapy in 12 hospitals ( n = 1121). We compared their DFS according to LNR, with a cut-off value of 0.10. The median follow-up period was 66 months (range, 3-112). Treatment failed in 73 patients (6.5%) and there was no significant difference in DFS between the SCNRT group and non-SCNRT group. High LNR (>0.10) showed significantly worse DFS in both univariate and multivariate analyses (0.010 and 0.033, respectively). In a subgroup analysis, the effect of SCNRT on DFS differed significantly among patients with LNR > 0.10 ( p = 0.013). High LNR can be used as an independent prognostic factor for pN1 breast cancer patients treated with partial mastectomy and postoperative radiotherapy. It may also be useful in deciding whether to perform SCNRT to improve DFS.

Metformin is a first-line medication for type 2 diabetes mellitus (T2DM). Based on its universal use, the consideration of inter-individual variability and development of predictive biomarkers are clinically significant. We aimed to identify endogenous markers of metformin responses using a pharmacometabolomic approach. Twenty-nine patients with early-phase T2DM were enrolled and orally administered metformin daily for 6 months. A total of 22 subjects were included in the final analysis. Patients were defined as responders or non-responders based on changes in their glycated haemoglobin A1c (HbA1c) from baseline, over 3 months. Urine metabolites at baseline, as well as at the 3 and 6 month follow-ups after the start of treatment were analysed using gas chromatography-mass spectrometry and evaluated with multivariate analyses. Metabolites distinguishable between the two response groups were obtained at baseline, as well as at the 3 and 6 month follow-ups, and significantly different metabolites were listed as markers of metformin response. Among the identified metabolites, citric acid, myoinositol, and hippuric acid levels showed particularly significant differences between the non-responder and responder groups. We thus identified different metabolite profiles in the two groups of T2DM patients after metformin administration, using pharmacometabolomics. These results might facilitate a better understanding and prediction of metformin response and its variability in individual patients.

Green tea is consumed as a beverage worldwide and has beneficial effects, such as a lower risk of cardiovascular disease and cancer. A quantitative analysis of the beneficial components in plasma is important for understanding the potential health benefits of green tea. Four catechins—epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epicatechin (EC)—which account for the majority of the components of green tea, were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, a validated method was optimized to obtain the blood concentrations after the one-time ingestion of 630 mg green tea extract with digoxin and then after the ingestion of 630 mg green tea repeatedly for 15 days. The calibration curve, including the LLOQ, was constructed over 1⁻500 ng/mL for EGCG, ECG, and EGC and 0.1⁻50 ng/mL for EC. The method for inter- and intra-validation was applied, acceptable for both accuracy and precision. We successfully developed an appropriate UPLC-MS/MS method for human plasma with good reproducibility and sensitivity. Thus, this method could be applied for future preclinical and clinical studies on EGCG, ECG, EGC, and EC.

We produced poro-us poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) composite scaffolds for bone regeneration, which can have a tailored macro/micro-porous structure with high mechanical properties and excellent in vitro bioactivity using non-solvent-induced phase separation (NIPS)-based 3D plotting. This innovative 3D plotting technique can create highly microporous PCL/HA composite filaments by inducing unique phase separation in PCL/HA solutions through the non-solvent-solvent exchange phenomenon. The PCL/HA composite scaffolds produced with various HA contents (0 wt %, 10 wt %, 15 wt %, and 20 wt %) showed that PCL/HA composite struts with highly microporous structures were well constructed in a controlled periodic pattern. Similar levels of overall porosity (~78 vol %) and pore size (~248 µm) were observed for all the PCL/HA composite scaffolds, which would be highly beneficial to bone tissue regeneration. Mechanical properties, such as ultimate tensile strength and compressive yield strength, increased with an increase in HA content. In addition, incorporating bioactive HA particles into the PCL polymer led to remarkable enhancements in in vitro apatite-forming ability., Competing Interests: The authors declare no conflict of interest.

Abstract : Stable isotope tracers were first applied to evaluate the Microcystis cell assimilation efficiency of Sinanodonta bivalves, since the past identification method has been limited to tracking the changes of each chl- a , clearity, and nutrient. The toxicity profile and accumulation of MC-LR, -RR and -YR in different organs (foot and digestive organs) from the three filter-feeders (Sinanodonta woodina, Sinanodonta arcaeformis, and Unio douglasiae) were assessed under the condition of toxigenic cyanobacteria (Microcystis aeruginosa) blooms through an in situ pond experiment using 13 C and 15 N dual isotope tracers. Chl- a concentration in the manipulated pond was dramatically decreased after the beginning of the second day, ranging from 217.5 to 15.6 μg·L -1 . The highest amount of MCs was incorporated into muscle and gland tissues in U. douglasiae during the study period, at nearly 2 or 3 times higher than in S . woodiana and S. arcaeformis. In addition, the incorporated 13 C and 15 N atom % in the U. douglasiae bivalve showed lower values than in other bivalves. The results demonstrate that U. douglasiae has less capacity to assimilate toxic cyanobacteria derived from diet. However, the incorporated 13 C and 15 N atom % of S . arcaeformis showed a larger feeding capacity than U. douglasiae and S . wodiana . Our results therefore also indicate that S . arcaeformis can eliminate the toxin more rapidly than U. douglasiae , having a larger detoxification capacity., Competing Interests: The authors declare no conflicts of interest.

Stem cells from human exfoliated deciduous tooth (SHED) offer several advantages over other stem cell sources. Using SHED, we examined the roles of zinc and the zinc uptake transporter ZIP8 (Zrt- and irt-like protein 8) while inducing SHED into insulin secreting β cell-like stem cells (i.e., SHED-β cells). We observed that ZIP8 expression increased as SHED differentiated into SHED-β cells, and that zinc supplementation at day 10 increased the levels of most pancreatic β cell markers-particularly Insulin and glucose transporter 2 (GLUT2). We confirmed that SHED-β cells produce insulin successfully. In addition, we note that zinc supplementation significantly increases insulin secretion with a significant elevation of ZIP8 transporters in SHED-β cells. We conclude that SHED can be converted into insulin-secreting β cell-like cells as zinc concentration in the cytosol is elevated. Insulin production by SHED-β cells can be regulated via modulation of zinc concentration in the media as ZIP8 expression in the SHED-β cells increases., Competing Interests: The authors declare no conflict of interest.

After in situ incubation at the site for a year, phytoplanktons in surface water were exposed to natural light in temperate lakes (every month); thereafter, the net production rate of photoprotective compounds (mycosporine-like amino acids, MAAs) was calculated using (13)C labeled tracer. This is the first report describing seasonal variation in the net production rate of individual MAAs in temperate lakes using a compound-specific stable isotope method. In the mid-latitude region of the Korean Peninsula, UV radiation (UVR) usually peaks from July to August. In Lake Paldang and Lake Cheongpyeong, diatoms dominated among the phytoplankton throughout the year. The relative abundance of Cyanophyceae (Anabaena spiroides) reached over 80% during July in Lake Cheongpyeong. Changes in phytoplankton abundance indicate that the phytoplankton community structure is influenced by seasonal changes in the net production rate and concentration of MAAs. Notably, particulate organic matter (POM) showed a remarkable change based on the UV intensity occurring during that period; this was because of the fact that cyanobacteria that are highly sensitive to UV irradiance dominated the community. POM cultured in Lake Paldang had the greatest shinorine (SH) production rate during October, i.e., 83.83 ± 10.47 fgC·L(-1)·h(-1). The dominance of diatoms indicated that they had a long-term response to UVR. Evaluation of POM cultured in Lake Cheongpyeong revealed that there was an increase in the net MAA production in July (when UVR reached the maximum); a substantial amount of SH, i.e., 17.62 ± 18.34 fgC·L(-1)·h(-1), was recorded during this period. Our results demonstrate that both the net production rate as well as the concentration of MAAs related to photoinduction depended on the phytoplankton community structure. In addition, seasonal changes in UVR also influenced the quantity and production of MAAs in phytoplanktons (especially Cyanophyceae).