Real-time chlorophyll-a forecasting using machine learning framework with dimension reduction and hyperspectral data.

Since water is an essential resource in various fields, it requires constant monitoring. Chlorophyll-a concentration is a crucial indicator of water quality and can be used to monitor water quality. In this study, we developed methods to forecast chlorophyll-a concentrations in real-time using hyperspectral data on IoT platform and various machine learning algorithms. Compared to regular cameras that record information only in the three broad color bands of red, green, and blue, the hyperspectral images of drinking water sources record the data in dozens or even hundreds of distinct small wavelength bands, providing each pixel in an image with a full spectrum. Different machine learning algorithms have been developed using hyperspectral data and field observations of water quality and weather conditions. Previous studies have predicted chlorophyll concentrations using either partial least squares (PLS), which is a dimensionality reduction method, or machine learning. In contrast, our study employed the PLS technique as a preprocessing step to diminish the dimensionality of the hyperspectral data, followed by the application of the machine learning techniques with optimized hyperparameters to improve the precision of the predictions, thereby introducing a real-time mechanism for chlorophyll-a prediction. Consequently, a machine learning algorithm with R2 values of 0.9 or above and sufficiently small RMSE was developed for real-time chlorophyll-a forecasting. Real-time chlorophyll-a forecasting using LightGBM has the best performance, with a mean R2 of 0.963 and a mean RMSE of 2.679. This paper is expected to have applications in algal bloom early detection on monitoring systems.

Synthesis and Optical Properties of One Year Air-Stable Chiral Sb(III) Halide Semiconductors.

Chiral hybrid metal-halide semiconductors (MHS) pose as ideal candidates for spintronic applications owing to their strong spin-orbit coupling (SOC), and long spin relaxation times. Shedding light on the underlying structure-property relationships is of paramount importance for the targeted synthesis of materials with an optimum performance. Herein, we report the synthesis and optical properties of 1D chiral (R-/S-THBTD)SbBr5 (THBTD = 4,5,6,7-tetrahydro-benzothiazole-2,6-diamine) semiconductors using a multifunctional ligand as a countercation and a structure directing agent. (R-/S-THBTD)SbBr5 feature direct and indirect band gap characteristics, exhibiting photoluminescence (PL) light emission at RT that is accompanied by a lifetime of a few ns. Circular dichroism (CD), second harmonic generation (SHG), and piezoresponse force microscopy (PFM) studies validate the chiral nature of the synthesized materials. Density functional theory (DFT) calculations revealed a Rashba/Dresselhaus (R/D) spin splitting, supported by an energy splitting (ER) of 23 and 25 meV, and a Rashba parameter (αR) of 0.23 and 0.32 eV·Å for the R and S analogs, respectively. These values are comparable to those of the 3D and 2D perovskite materials. Notably, (S-THBTD)SbBr5 has been air-stable for a year, a record performance among chiral lead-free MHS. This work demonstrates that low-dimensional, lead-free, chiral semiconductors with exceptional air stability can be acquired, without compromising spin splitting and manipulation performance.

Effects of hole transporting PEDOT:PSS on the photoemission of upconverted hot electron in Mn-doped CdS/ZnS quantum dots.

In this work, we investigated the effect of hole transporting poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) interfacing with Mn-doped CdS/ZnS quantum dots (QDs) deposited on an indium tin oxide (ITO) substrate on the photoemission of upconverted hot electrons under weak continuous wave photoexcitation in a vacuum. Among the various factors that can influence the photoemission of the upconverted hot electrons, we studied the role of PEDOT:PSS in facilitating the hole transfer from QDs and altering the energy of photoemitted hot electrons. Compared to hot electrons emitted from QDs deposited directly on the ITO substrate, the addition of the PEDOT:PSS layer between the QD and ITO layers increased the energy of the photoemitted hot electrons. The increased energy of the photoemitted hot electrons is attributed in part to the reduced steady-state positive charge on the QDs under continuous photoexcitation, which reduces the energy required to eject the electron from the conduction band.

Spatiotemporally controlled drug delivery via photothermally driven conformational change of self-integrated plasmonic hybrid nanogels.

BACKGROUND: Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. RESULTS: In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. CONCLUSION: This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery.

Covalent Scrambling in Porous Polyarylthioethers through a Stepwise SN Ar for Tunable Bandgap and Porosity.

Porous poly(aryl thioether)s offer stability and electronic tunability by robust sulfur-aryl conjugated architecture, but synthetic access is hindered due to limited control over the nucleophilic nature of sulfides and the air sensitivity of aromatic thiols. Here, we report a simple, one-pot, inexpensive, regioselective synthesis of highly porous poly(aryl thioether)s through polycondensation of perfluoroaromatic compounds with sodium sulfide. The unprecedented temperature-dependent para-directing formation of thioether linkages leads to a stepwise transition of the polymer extension into a network, thereby allowing fine control of the porosity and optical band gaps. The obtained porous organic polymers with ultra-microporosity (<1 nm) and sulfur as the surface functional groups show size-dependent separation of organic micropollutants and selective removal of mercury ions from water. Our findings offer easy access to poly(aryl thioether)s with accessible sulfur functionalities and higher complexity, which will help in realizing advanced synthetic designs in applications such as adsorption, (photo)catalysis, and (opto)electronics.

Systematic Modulation of Thiol Functionalities in Inexpensive Porous Polymers for Effective Mercury Removal.

Through accumulation, mercury contamination in aquatic systems still poses serious health risks despite the strict regulations on drinking water and industrial discharge. One effective strategy against this is adsorptive removal, in which a suitably functionalized porous material is added to water treatment protocols. Thiol (SH) group-grafted structures perform commendably; however, insufficient attention is paid to the cost, scalability, and reusability or how the arrangement of sulfur atoms could affect the HgII binding strength. We used an inexpensive and scalable porous covalent organic polymer (COP-130) to systematically introduce thiol functional groups with precise chain lengths and sulfur content. Thiol-functionalized COP-130 demonstrates enhanced wettability and excellent HgII uptake of up to 936 mg g-1 , with fast kinetics and exceptionally high selectivity. These Hg adsorbents are easily regenerated with HCl and can be used at least six times without loss of capacity even after treatment with strong acid, a rare performance in the domain of Hg-removal research.

Anomaly Detection with Feature Extraction Based on Machine Learning Using Hydraulic System IoT Sensor Data.

Hydraulic systems are advanced in function and level as they are used in various industrial fields. Furthermore, condition monitoring using internet of things (IoT) sensors is applied for system maintenance and management. In this study, meaningful features were identified through extraction and selection of various features, and classification evaluation metrics were presented through machine learning and deep learning to expand the diagnosis of abnormalities and defects in each component of the hydraulic system. Data collected from IoT sensor data in the time domain were divided into clusters in predefined sections. The shape and density characteristics were extracted by cluster. Among 2335 newly extracted features, related features were selected using correlation coefficients and the Boruta algorithm for each hydraulic component and used for model learning. Linear discriminant analysis (LDA), logistic regression, support vector classifier (SVC), decision tree, random forest, XGBoost, LightGBM, and multi-layer perceptron were used to calculate the true positive rate (TPR) and true negative rate (TNR) for each hydraulic component to detect normal and abnormal conditions. Valve condition, internal pump leakage, and hydraulic accumulator data showed TPR performance of 0.94 or more and a TNR performance of 0.84 or more. This study's findings can help to determine the stable and unstable states of each component of the hydraulic system and form the basis for engineers' judgment.

Stack LSTM-Based User Identification Using Smart Shoes with Accelerometer Data.

In this study, we propose a long short-term memory (LSTM)-based user identification method using accelerometer data from smart shoes. In general, for the user identification with human walking data, we require a pre-processing stage in order to divide human walking data into individual steps. Next, user identification can be made with divided step data. In these approaches, when there exist partial data that cannot complete a single step, it is difficult to apply those data to the classification. Considering these facts, in this study, we present a stack LSTM-based user identification method for smart-shoes data. Rather than using a complicated analysis method, we designed an LSTM network for user identification with accelerometer data of smart shoes. In order to learn partial data, the LSTM network was trained using walking data with random sizes and random locations. Then, the identification can be made without any additional analysis such as step division. In the experiments, user walking data with 10 m were used. The experimental results show that the average recognition rate was about 93.41%, 97.19%, and 98.26% by using walking data of 2.6, 3.9, and 5.2 s, respectively. With the experimental results, we show that the proposed method can classify users effectively.

Developing neural network models for early detection of cardiac arrest in emergency department.

BACKGROUND: Automated surveillance for cardiac arrests would be useful in overcrowded emergency departments. The purpose of this study is to develop and test artificial neural network (ANN) classifiers for early detection of patients at risk of cardiac arrest in emergency departments. METHODS: This is a single-center electronic health record (EHR)-based study. The primary outcome was the development of cardiac arrest within 24 h after prediction. Three ANN models were trained: multilayer perceptron (MLP), long-short-term memory (LSTM), and hybrid. These were compared to other classifiers including the modified early warning score (MEWS), logistic regression, and random forest. We used AUROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the comparison. RESULTS: During the study period, there were a total of 374,605 ED visits and 2,910,321 patient status updates. The ANN models (MLP, LSTM, and hybrid) achieved higher AUROC (AUROC: 0.929, 0.933, and 0.936; 95% confidential interval: 0.926-0.932, 0.930-0.936, and 0.933-0.939, respectively) compared to the non-ANN models, and the hybrid model exhibited the best performance. The ANN classifiers displayed higher performance in most of the test characteristics when the threshold levels of the classifiers were fixed to display the same positive result as those at the three MEWS thresholds (score ≥ 3, ≥4, and ≥5), and when compared with each other. CONCLUSIONS: The ANN improves upon MEWS and conventional machine learning algorithms for the prediction of cardiac arrests in emergency departments. The hybrid ANN model utilizing both baseline and sequence information achieved the best performance.

Characterization of Fecal Peritonitis-Induced Sepsis in a Porcine Model.

BACKGROUND: Although there are well-established small-animal sepsis models, the longitudinal assessment of hemodynamic variables, laboratory values, and blood culture in a single living sepsis model is limited. Therefore, we aimed to comprehensively characterize fecal peritonitis-induced sepsis in a porcine model. MATERIALS AND METHODS: Autologous feces (1 g/kg) was administered into the peritoneum of 11 male pigs (49 ± 8 kg). The pigs were monitored up to 12 h with full fluid and vasopressor support to maintain the mean arterial pressure at >65 mm Hg. Longitudinal blood culture and laboratory values were obtained at defined time intervals. The cytokine levels in plasma were analyzed. Furthermore, a clinical registry of sepsis patients at a single emergency department was used to compare the Sepsis-related Organ Failure Assessment scores with those of the porcine model. RESULTS: The hyperdynamic phase of increasing cardiac output with decreasing systemic vascular resistance was maintained until 2 h, followed by the reverse (hypodynamic phase). With the escalating requirement for fluid and vasopressor, the lactate level progressively increased while the platelet count, urine output, and serum albumin level consistently decreased. Bacteremia developed 7 h (median) after the administration of feces, and Escherichia coli was the most common pathogen. The pattern of Sepsis-related Organ Failure Assessment scores with prominent cardiovascular failure was comparable to clinical data. CONCLUSIONS: We implemented a porcine fecal peritonitis-induced sepsis model that demonstrates culture-proven bacteremia and multiple organ failure, particularly cardiovascular system failure. This model could facilitate the development of technologies for the early diagnosis of bacterial pathogens in blood.

MRPrimerV: a database of PCR primers for RNA virus detection.

Many infectious diseases are caused by viral infections, and in particular by RNA viruses such as MERS, Ebola and Zika. To understand viral disease, detection and identification of these viruses are essential. Although PCR is widely used for rapid virus identification due to its low cost and high sensitivity and specificity, very few online database resources have compiled PCR primers for RNA viruses. To effectively detect viruses, the MRPrimerV database (http://MRPrimerV.com) contains 152 380 247 PCR primer pairs for detection of 1818 viruses, covering 7144 coding sequences (CDSs), representing 100% of the RNA viruses in the most up-to-date NCBI RefSeq database. Due to rigorous similarity testing against all human and viral sequences, every primer in MRPrimerV is highly target-specific. Because MRPrimerV ranks CDSs by the penalty scores of their best primer, users need only use the first primer pair for a single-phase PCR or the first two primer pairs for two-phase PCR. Moreover, MRPrimerV provides the list of genome neighbors that can be detected using each primer pair, covering 22 192 variants of 532 RefSeq RNA viruses. We believe that the public availability of MRPrimerV will facilitate viral metagenomics studies aimed at evaluating the variability of viruses, as well as other scientific tasks.

Precise Control of Quantum Confinement in Cesium Lead Halide Perovskite Quantum Dots via Thermodynamic Equilibrium.

Cesium lead halide (CsPbX3) nanocrystals have emerged as a new family of materials that can outperform the existing semiconductor nanocrystals due to their superb optical and charge-transport properties. However, the lack of a robust method for producing quantum dots with controlled size and high ensemble uniformity has been one of the major obstacles in exploring the useful properties of excitons in zero-dimensional nanostructures of CsPbX3. Here, we report a new synthesis approach that enables the precise control of the size based on the equilibrium rather than kinetics, producing CsPbX3 quantum dots nearly free of heterogeneous broadening in their exciton luminescence. The high level of size control and ensemble uniformity achieved here will open the door to harnessing the benefits of excitons in CsPbX3 quantum dots for photonic and energy-harvesting applications.

Highly palatable food access during adolescence increased anxiety-/depression-like behaviors in male, but not in female, rats.

OBJECTIVES: This study was conducted to examine the sexual dimorphic effects of highly palatable food (HPF) access during adolescence on the neurochemistry and depression-/anxiety-like behaviors of rats. METHODS: Male and female Sprague-Dawley pups had free access to chocolate cookie rich in fat (HPF) from postnatal day 28 in addition to ad libitum chow, and the control groups received only chow. The food conditions were continued throughout the entire experimental period, and the neurochemical and behavioral measurements were performed during young adulthood. Rats were subjected to the ambulatory activity, elevated plus maze, and forced swim tests. Corticosterone levels during 2 h of restraint stress were analyzed with radioimmunoassay, and ΔFosB and brain-derived neurotrophic factor (BDNF) expression in the nucleus accumbens (NAc) with Western blot analysis. RESULTS: Cookie access did not affect body weight gain and total caloric intake in both sexes; however, it increased retroperitoneal fat depot only in males. The time spent in open arms during elevated plus maze test was decreased and immobility during forced swim test was increased in cookie-fed males, but not in cookie-fed females. Main effect of food condition on the stress-induced corticosterone increase was observed in males, but not in females, and cookie access increased BDNF expression in the NAc only in males. CONCLUSIONS: Increased BDNF expression in the NAc and fat depot, in addition to the stress axis dysfunction, may play roles in the pathophysiology of depression- and/or anxiety-like behaviors induced by cookie access.

Effects of Direct Solvent-Quantum Dot Interaction on the Optical Properties of Colloidal Monolayer WS2 Quantum Dots.

Because of the absence of native dangling bonds on the surface of the layered transition metal dichalcogenides (TMDCs), the surface of colloidal quantum dots (QDs) of TMDCs is exposed directly to the solvent environment. Therefore, the optical and electronic properties of TMDCS QDs are expected to have stronger influence from the solvent than usual surface-passivated QDs due to more direct solvent-QD interaction. Study of such solvent effect has been difficult in colloidal QDs of TMDC due to the large spectroscopic heterogeneity resulting from the heterogeneity of the lateral size or (and) thickness in ensemble. Here, we developed a new synthesis procedure producing the highly uniform colloidal monolayer WS2 QDs exhibiting well-defined photoluminescence (PL) spectrum free from ensemble heterogeneity. Using these newly synthesized monolayer WS2 QDs, we observed the strong influence of the aromatic solvents on the PL energy and intensity of monolayer WS2 QD beyond the simple dielectric screening effect, which is considered to result from the direct electronic interaction between the valence band of the QDs and molecular orbital of the solvent. We also observed the large effect of stacking/separation equilibrium on the PL spectrum dictated by the balance between inter QD and QD-solvent interactions. The new capability to probe the effect of the solvent molecules on the optical properties of colloidal TMDC QDs will be valuable for their applications in various liquid surrounding environments.

Decreased hippocampal brain-derived neurotrophic factor and impaired cognitive function by hypoglossal nerve transection in rats.

The hypoglossal nerve controls tongue movements, and damages of it result in difficulty in mastication and food intake. Mastication has been reported to maintain hippocampus-dependent cognitive function. This study was conducted to examine the effect of tongue motor loss on the hippocampus-dependent cognitive function and its underlying mechanism. Male Sprague Dawley rats were subjected to the initial training of Morris water maze task before or after the bilateral transection of hypoglossal nerves (Hx). When the initial training was given before the surgery, the target quadrant dwelling time during the probe test performed at a week after the surgery was significantly reduced in Hx rats relative to sham-operated controls. When the initial training was given after the surgery, Hx affected the initial and reversal trainings and probe tests. Brain-derived neurotrophic factor (BDNF) expression, cell numbers and long-term potentiation (LTP) were examined in the hippocampus on the 10th day, and BrdU and doublecortin staining on the 14th day, after the surgery. Hx decreased the hippocampal BDNF and cells in the CA1/CA3 regions and impaired LTP. BrdU and doublecortin staining was decreased in the dentate gyrus of Hx rats. Results suggest that tongue motor loss impairs hippocampus-dependent cognitive function, and decreased BDNF expression in the hippocampus may be implicated in its underlying molecular mechanism in relation with decreased neurogenesis/proliferation and impaired LTP.

Simultaneous determination of ß-sitosterol, campesterol, and stigmasterol in rat plasma by using LC-APCI-MS/MS: Application in a pharmacokinetic study of a titrated extract of the unsaponifiable fraction of Zea mays L.

A liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry method was developed and validated to investigate the pharmacokinetic properties of ß-sitosterol, campesterol, and stigmasterol in rat plasma. Cholesterol-d6 was used as an internal standard. To avoid interference of the three phytosterols in rat plasma and minimize matrix effects, a small volume (10 µL) of 4% bovine serum albumin was used as a surrogate matrix for making calibrators and quality control samples. Rat plasma (10 µL) samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a Kinetex C18 column. The detection was performed on a triple quadrupole tandem mass spectrometer in selected reaction monitoring mode using positive atmospheric pressure chemical ionization. This assay was linear over concentration ranges of 250-5000 ng/mL (ß-sitosterol), 250-5000 ng/mL (campesterol), and 50-2000 ng/mL (stigmasterol). Additionally, a second set of quality controls made in rat plasma was also evaluated against calibration curves made using the surrogate matrix. All the validation data, including the specificity, precision, accuracy, recovery, matrix effect, stability, and incurred sample reanalysis conformed to the acceptance requirements. Our method was successfully applied to study the pharmacokinetics of three phytosterols in rats.

In Vitro Inhibition of Human UDP-Glucuronosyl-Transferase (UGT) Isoforms by Astaxanthin, ß-Cryptoxanthin, Canthaxanthin, Lutein, and Zeaxanthin: Prediction of in Vivo Dietary Supplement-Drug Interactions.

Despite the widespread use of the five major xanthophylls astaxanthin, ß-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for ß-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. ß-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 µM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 µM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 µM, respectively. Among the tested xanthophyll-UGT pairs, ß-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 µM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of ß-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls.

Pharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in rats.

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea. This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed. 6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

Metabolic drug-drug interaction potential of macrolactin A and 7-O-succinyl macrolactin A assessed by evaluating cytochrome P450 inhibition and induction and UDP-glucuronosyltransferase inhibition in vitro.

Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with Ki values of 4.06 µM and 10.6 µM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with Ki values of 40.1 µM and 65.3 µM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism in vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo. Although further investigations will be required to clarify the in vivo interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.

Encapsulated stretchable amphibious strain sensors.

Soft and stretchable strain sensors have found wide applications in health monitoring, motion tracking, and robotic sensing. There is a growing demand for strain sensors in amphibious environments, such as implantable sensors, wearable sensors for swimmers/divers, and underwater robotic sensors. However, developing a sensitive, stretchable, and robust amphibious strain sensor remains challenging. This work presents an encapsulated stretchable amphibious strain sensor. The conductive layer, made of silver nanowires embedded below the surface of polydimethylsiloxane, was sandwiched by two layers of thermoplastic polyurethane. Periodic sharp cuts were introduced to change the direction of flow from across the sensor to along the conductive path defined by the opening cracks. The crack advancing and opening is controlled by a unique combination of weak/strong interfaces within the sandwich structure. The cut design and the interfacial interactions between the layers were investigated. The strain sensor exhibited a high gauge factor up to 289, a linear sensing response, a fast response time (53 ms), excellent robustness against over-strain, and stability after 16 000 loading cycles and 20 days in an aqueous saline solution. The functionality of this amphibious strain sensor was demonstrated by tracking the motion of a robotic fish, undertaking language recognition underwater, and monitoring the blood pressure of a porcine aorta. This illustrates the promising potential for this strain sensor for both underwater use and surgically implantable applications.