Revealing the Loss Mechanism of Chemically-Induced Hot Electron Transport.

Hot electrons are crucial for unraveling the intrinsic relationship between chemical reactions and charge transfer in heterogeneous catalysis. Significant research focused on real-time detection of reaction-driven hot electron flow (chemicurrent) to elucidate the energy conversion mechanisms, but it remains elusive because carrier generation contributes to only part of the entire process. Here, a theoretical model for quantifying the chemicurrent yield is presented by clarifying the contributions of hot carrier losses from the internal emission and multiple reflections. The experimental chemicurrent yield verifies our model with a reliable mean free path of hot electrons, emphasizing the importance of comprehensive consideration of the transport process besides hot electron generation. Moreover, Pt nanoparticles (NPs)-decorated Au/TiO2 is examined, showing the role of NPs-induced carrier losses in the performance of catalytic nanodiodes. These findings are expected to contribute to understanding the hot electron detection efficiency and designing nanodiodes with enhanced hot carrier flow and catalytic activity.

Development of Scaffold-Free Three-Dimensional Cholangiocyte Organoids to Study the Progression of Primary Sclerosing Cholangitis.

Organoids are novel in vitro models to study intercellular cross talk between the different types of cells in disease pathophysiology. To better understand the underlying mechanisms driving the progression of primary sclerosing cholangitis (PSC), scaffold-free multicellular three-dimensional cholangiocyte organoids (3D-CHOs) were developed using primary liver cells derived from normal subjects and patients with PSC. Human liver samples from healthy donors and patients with PSC were used to isolate primary cholangiocytes [epithelial cell adhesion molecule (EpCam)+/ cytokeratin-19+], liver endothelial cells (CD31+), and hepatic stellate cells (HSCs; CD31-/CD68-/desmin+/vitamin A+). 3D-CHOs were formed using cholangiocytes, HSCs, and liver endothelial cells, and kept viable for up to 1 month. Isolated primary cell lines and 3D-CHOs were further characterized by immunofluorescence, quantitative RT-PCR, and transmission electron microscopy. Transcription profiles for cholangiocytes (SOX9, CFTR, EpCAM, AE, SCT, and SCTR), fibrosis (ACTA2, COL1A1, DESMIN, and TGFß1), angiogenesis (PECAM, VEGF, CDH5, and vWF), and inflammation (IL-6 and TNF-α) confirmed PSC phenotypes of 3D-CHOs. Because cholangiocytes develop a neuroendocrine phenotype and express neuromodulators, confocal immunofluorescence was used to demonstrate localization of the neurokinin-1 receptor within cytokeratin-19+ cholangiocytes and desmin+ HSCs. Moreover, 3D-CHOs from patients with PSC confirmed PSC phenotypes with up-regulated neurokinin-1 receptor, tachykinin precursor 1, and down-regulated membrane metalloendopeptidase. Scaffold-free multicellular 3D-CHOs showed superiority as an in vitro model in mimicking PSC in vivo phenotypes compared with two-dimensional cell culture, which can be used in PSC disease-related research.

Thiazol-4(5H)-one analogs as potent tyrosinase inhibitors: Synthesis, tyrosinase inhibition, antimelanogenic effect, antioxidant activity, and in silico docking simulation.

As the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC50 value of 0.4 ± 0.01 µM, which indicates its 26-fold greater potency than kojic acid. Kinetic studies using Lineweaver-Burk plots revealed that 9 and 11 are competitive and mixed-type inhibitors, respectively; these kinetic results were supported by docking simulations. According to the B16F10 cell-based experiments, 9 and 11 inhibited melanogenesis more effectively than kojic acid due to their potent cellular tyrosinase inhibitory activity. In addition, analogs 9 and 11 exhibited moderate-to-strong antioxidant capacity, scavenging ABTS+, DPPH, and ROS radicals. In particular, analog 12 with a catechol moiety exhibited very strong ROS-scavenging activity, similar to Trolox. These results suggest that analogs 9 and 11, which exhibit potent tyrosinase inhibitory activity in mushroom and mammalian cells and anti-melanogenic effects in B16F10 cells, are promising antibrowning agents for crops and skin lightening agents for hyperpigmentation-related diseases.

Highly potent anti-melanogenic effect of 2-thiobenzothiazole derivatives through nanomolar tyrosinase activity inhibition.

Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC50 values of 0.02-0.83 µM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders.

Preliminary report of Mycoplasma Wenoynii and Candidatus Mycoplasma haemobos infection in Korean native cattle.

BACKGROUND: Hemotropic mycoplasmas or hemoplasmas are bacteria that attach to the erythrocyte surface and cause bovine hemoplasmosis. Two species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been identified and shown to be distributed worldwide. However, there is currently no information available on hemoplasmas in cattle in the Republic of Korea. The aim of this study was to investigate the presence of hemoplasmas in Korean native cattle and to evaluate the association between hemoplasma infection and anemia. METHODS: One farm was selected, at which blood samples were collected from 104 Korean native cattle [grazing cattle (n = 89) and housed cattle (n = 15)]. Hemoplasmas were detected via polymerase chain reaction analysis and complete blood counts were also performed. RESULTS: The overall prevalence of hemoplasmas was 34% (35/104); 20.2% (21/104) for M. wenyonii, 3.8% (4/104) for C. M. haemobos, and 9.6% (10/104) for co-infection. Candidatus Mycoplasma haemobos was detected only in grazing cattle. Of red blood cell (RBC) parameters, C. M. haemobos-infected cattle had lower RBC and hematocrit, and higher mean cell volume than hemoplasma-negative cattle, although none of these differences were statistically significant. This is the first study to report the occurrence of M. wenyonii and C. M. haemobos. Mycoplasma wenyonii is more prevalent than C. M. haemobos in Korean native cattle. The results did not show an association between hemoplasma infection and anemia. CONCLUSIONS: Considering the infection rate of hemoplasmas shown in this study, further studies, such as on the pathogenicity and clinical significance of hemoplasmas are necessary.

Sensors and Sensing Devices Utilizing Electrorheological Fluids and Magnetorheological Materials-A Review.

This paper comprehensively reviews sensors and sensing devices developed or/and proposed so far utilizing two smart materials: electrorheological fluids (ERFs) and magnetorheological materials (MRMs) whose rheological characteristics such as stiffness and damping can be controlled by external stimuli; an electrical voltage for ERFs and a magnetic field for MRMs, respectively. In this review article, the MRMs are classified into magnetorheological fluids (MRF), magnetorheological elastomers (MRE) and magnetorheological plastomers (MRP). To easily understand the history of sensing research using these two smart materials, the order of this review article is organized in a chronological manner of ERF sensors, MRF sensors, MRE sensors and MRP sensors. Among many sensors fabricated from each smart material, one or two sensors or sensing devices are adopted to discuss the sensing configuration, working principle and specifications such as accuracy and sensitivity. Some sensors adopted in this article include force sensors, tactile devices, strain sensors, wearable bending sensors, magnetometers, display devices and flux measurement sensors. After briefly describing what has been reviewed in a conclusion, several challenging future works, which should be undertaken for the practical applications of sensors or/and sensing devices, are discussed in terms of response time and new technologies integrating with artificial intelligence neural networks in which several parameters affecting the sensor signals can be precisely and optimally tuned. It is sure that this review article is very helpful to potential readers who are interested in creative sensors using not only the proposed smart materials but also different types of smart materials such as shape memory alloys and active polymers.

Investigation of the Efficacy of Benzylidene-3-methyl-2-thioxothiazolidin-4-one Analogs with Antioxidant Activities on the Inhibition of Mushroom and Mammal Tyrosinases.

Based on the fact that substances with a ß-phenyl-α,ß-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.

Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus in vitro, intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases.

Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines.

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and is associated with late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.

Surface Plasmon-Induced Hot Carriers: Generation, Detection, and Applications.

ConspectusDuring surface plasmon-mediated light-matter interactions, external energies on plasmonic metal nanostructures undergo energy dissipation via elastic e-e scattering, radiative luminescence, and nonradiative processes such as thermal relaxation (phonon) and electronic excitation (electron-hole pairs). In this process, surface plasmon decays dominantly through nonradiative recombination when the metal is smaller than 25 nm, forming hot carriers, including hot electrons and hot holes, with high kinetic energy of 1-3 eV. Although the ultrafast dynamics of hot carriers are on time scales ranging from femtoseconds to picoseconds, these fast-disappearing hot carriers can be collected as the steady-state photocurrent or chemicurrent by adopting the metal-semiconductor (M-S)-based platform for detecting hot carrier flow. Plasmonic hot carriers, especially as they convert to an electrochemical signal, are a promising topic, and their energy conversion mechanisms are being actively studied in the fields of renewable energy, optoelectronics, and photocatalysis. Recent studies have demonstrated that these hot carriers can both improve the performance of solar energy conversion and control the catalytic activity or selectivity by directly participating in the photoelectrochemical (PEC) reaction.In this Account, we describe the inherent relationship between hot carriers and surface plasmon as well as what role hot carriers play throughout the catalytic reaction. The recent experimental work and the theoretical analysis of in situ hot carrier generation on Au nanostructures were conducted with photoconductive atomic force microscopy and finite-difference time-domain (FDTD) simulations, respectively. We highlight the recent nanoscale visualization of hot carrier flow occurring through light-matter interactions and that the localized surface plasmon field surrounding the Au nanostructure leads to boosted hot carrier generation. In addition, we highlight the recent demonstration that plasmonic hot carriers prolong the lifetime of photoexcited carriers in the MAPbI3/Au/TiO2 hybrid nanodiode by the synergistic effect between plasmonic Au and perovskites. From this work, the solar-to-electron conversion performance of this nanodiode significantly increases due to the amplification of light absorption, which helps to design hybrid platforms for efficient hot carrier photovoltaics. We discuss the application of surface plasmon-driven hot electron generation, including hot electron-based photovoltaic devices and photocatalysts. We highlight the recent photoelectrochemical measurements on the Au/p-GaN heterostructures that are controlled by participating plasmonic hot carriers in the water splitting reaction. Furthermore, controlling the flow of both hot electrons and holes by developing hybrid platform configurations for hot carrier applications has promising opportunities for regulating the catalytic activities of hot carrier-based photocatalysis and improving the photoconversion efficiency of hot carrier-based optoelectronic devices.

Higgsino Dark Matter Confronts 14 Years of Fermi γ-Ray Data.

Thermal Higgsino dark matter (DM), with mass around 1 TeV, is a well-motivated, minimal DM scenario that arises in supersymmetric extensions of the standard model. Higgsinos may naturally be the lightest superpartners in split-supersymmetry models that decouple the scalar superpartners while keeping Higgsinos and gauginos close to the TeV scale. Higgsino DM may annihilate today to give continuum γ-ray emission at energies less than a TeV in addition to a linelike signature at energies equal to the mass. Previous searches for Higgsino DM, for example with the H.E.S.S. γ-ray telescope, have not reached the necessary sensitivity to probe the Higgsino annihilation cross section. In this work we make use of 14 years of data from the Fermi Large Area Telescope at energies above ∼10 GeV to search for the continuum emission near the Galactic Center from Higgsino annihilation. We interpret our results using DM profiles from Milky Way analog galaxies in the FIRE-2 hydrodynamic cosmological simulations. We set the strongest constraints to date on Higgsino-like DM. Our results show a mild, ∼2σ preference for Higgsino DM with a mass near the thermal Higgsino mass and, depending on the DM density profile, the expected cross section.

Identification and molecular mechanism of novel 5-alkenyl-2-benzylaminothiazol-4(5H)-one analogs as anti-melanogenic and antioxidant agents.

Mushroom tyrosinase is a tetramer, whereas mammalian tyrosinase is a monomeric glycoprotein. In addition, the amino acid sequence of mushroom tyrosinases differs from that of mammalian tyrosinases. MHY2081 exhibits potent inhibitory activity against both mushroom and mammalian tyrosinases. Accordingly, based on the MHY2081 structure, 5-alkenyl-2-benzylaminothiazol-4(5H)-one analogs were designed as a novel anti-tyrosinase agent and synthesized using 2-((3,4-dimethoxybenzyl)amino)thiazol-4(5H)-one (16), a key intermediate obtained via the rearrangement of a benzylamino group. Compounds 6 and 9 (IC50 = 1.5-4.6 µM) exhibited higher mushroom tyrosinase inhibitory activity than kojic acid (IC50 = 20-21 µM) in the presence of l-tyrosine and/or l-dopa. Based on kinetic analysis using Lineweaver-Burk plots, 6 was a mixed inhibitor, whereas 9 was a competitive inhibitor, and docking simulation results supported that these compounds could bind to the active site of mushroom tyrosinase. Using B16F10 mammalian cells, we demonstrated that these compounds inhibited melanogenesis more potently than kojic acid, and their anti-melanogenic effects could be attributed to tyrosinase inhibition. All synthesized compounds could scavenge reactive oxygen species (ROS), with five compounds exhibiting mild-to-strong ABTS+ and DPPH radical-scavenging abilities. Compounds 6 and 9 were potent tyrosinase inhibitors with strong antioxidant activities against ROS, ABTS+, and DPPH radicals. Moreover, the compounds significantly suppressed tyrosinase expression in a dose-dependent manner. Collectively, these results suggest that the novel 5-alkenyl-2-benzylaminothiazol-4(5H)-one analogs, especially 6 and 9, are potential anti-melanogenic agents with antioxidant activity.

Anti-tyrosinase flavone derivatives and their anti-melanogenic activities: Importance of the ß-phenyl-α,ß-unsaturated carbonyl scaffold.

Flavone derivatives were designed and synthesized based on the hypothesis that flavones containing the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) scaffold have potential anti-tyrosinase activity. Flavones 1a and 1e inhibited mushroom tyrosinase more potently than kojic acid, and 1e inhibited monophenolase and diphenolase 61- and 28-fold more than kojic acid, respectively. Kinetic studies on mushroom tyrosinase indicated that 1a and 1e competitively inhibit monophenolase and diphenolase, and docking results supported these results. In an in vitro assay using B16F10 murine cells, 1a and 1e inhibited melanin production more potently than kojic acid, and this was attributed to the inhibition of tyrosinase. Furthermore, 1a and 1e strongly scavenged DPPH and ABTS radicals and ROS, which suggested that their antioxidant properties were at least partly responsible for their anti-melanogenic effects. Moreover, flavone 1a also inhibited the gene expressions of the melanogenesis-related genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Our findings that flavone derivatives (i) directly inhibit tyrosinase, (ii) act as antioxidants, and (iii) inhibit the expressions of melanogenesis-related genes suggest their potential use as natural melanogenesis inhibitors. Furthermore, the study confirms that the PUSC scaffold confers anti-tyrosinase activity.

A Novel Tactile Sensing System Utilizing Magnetorheological Structures for Dynamic Contraction and Relaxation Motions.

It is well known that the rheological properties of magnetorheological (MR) material change under a magnetic field. So far, most works on MR materials have been oriented toward actuating characteristics instead of sensing functions. In this work, to realize dynamic tactile motion, a spherical MR structure was designed as a sensor, incorporating a magnetic circuit core to provide maximum dynamic motion. After manufacturing a prototype (sample), a sinusoidal magnetic field of varying exciting frequency and magnitude was applied to the sample, and the dynamic contraction and relaxation motion depending on the exciting magnetic field was observed. Among the test results, when 10% deformation occurred, the instantaneous force generated was from 2.8 N to 8.8 N, and the force when relaxed was from 1.2 N to 3.5 N. It is also shown that the repulsive force within this range can be implemented using an acceptable input current. The special tactile sensing structure proposed in this work can be used as a sensor to measure the field-dependent viscoelastic properties of human tissues such as stomach, liver, and overall body. In addition, it could be usefully applied to robot surgery, because it can mimic the dynamic motions of various human organs under various surgical conditions.

Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects.

In this study, (Z)-2-(benzylamino)-5-benzylidenethiazol-4(5H)-one (BABT) derivatives were designed as tyrosinase inhibitors based on the structure of MHY2081, using a simplified approach. Of the 14 BABT derivatives synthesized, two derivatives ((Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one [7] and (Z)-2-(benzylamino)-5-(2,4-dihydroxybenzylidene)thiazol-4(5H)-one [8]) showed more potent mushroom tyrosinase inhibitory activities than kojic acid, regardless of the substrate used; in particular, compound 8 was 106-fold more potent than kojic acid when l-tyrosine was used as the substrate. Analysis of Lineweaver-Burk plots for 7 and 8 indicated that they were competitive inhibitors, which was confirmed via in silico docking. In experiments using B16F10 cells, 8 exerted a greater ability to inhibit melanin production than kojic acid, and it inhibited cellular tyrosinase activity in a concentration-dependent manner, indicating that the anti-melanogenic effect of 8 is attributable to its ability to inhibit tyrosinase. In addition, 8 exhibited strong antioxidant activity to scavenge 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and peroxynitrite and inhibited the expression of melanogenesis-associated proteins (tyrosinase and microphthalmia-associated transcription factor). These results suggest that BABT derivative 8 is a promising candidate for the treatment of hyperpigmentation-related diseases, owing to its inhibition of melanogenesis-associated protein expression, direct tyrosinase inhibition, and antioxidant activity.

Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5H)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds.

(Z)-5-Benzylidene-2-phenylthiazol-4(5H)-one ((Z)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (Z)-BPTs 1-14, was determined based on the 3JC,Hß coupling constant of 1H-coupled 13C NMR spectra. Three (Z)-BPT derivatives (1-3) showed stronger tyrosinase inhibitory activities than kojic acid; in particular, 2 was to be 189-fold more potent than kojic acid. Kinetic analysis using mushroom tyrosinase indicated that 1 and 2 were competitive inhibitors, whereas 3 was a mixed-type inhibitor. The in silico results revealed that 1-3 could strongly bind to the active sites of mushroom and human tyrosinases, supporting the kinetic results. Derivatives 1 and 2 decreased the intracellular melanin contents in a concentration-dependent manner in B16F10 cells, and their anti-melanogenic efficacy exceeded that of kojic acid. The anti-tyrosinase activity of 1 and 2 in B16F10 cells was similar to their anti-melanogenic effects, suggesting that their anti-melanogenic effects were primarily owing to their anti-tyrosinase activity. Western blotting of B16F10 cells revealed that the derivatives 1 and 2 inhibited tyrosinase expression, which partially contributes to their anti-melanogenic ability. Several derivatives, including 2 and 3, exhibited potent antioxidant activities against ABTS cation radicals, DPPH radicals, ROS, and peroxynitrite. These results suggest that (Z)-BPT derivatives 1 and 2 have promising potential as novel anti-melanogenic agents.

Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease.

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. There is a great need for an efficient and reliable "human" in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of three-dimensional (3D) liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells versus primary cell lines and human versus murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.

Synergistic Effect of Q203 Combined with PBTZ169 against Mycobacterium tuberculosis.

Q203 is a first-in-class drug candidate against Mycobacterium tuberculosis. In its recently completed phase 2 clinical trial, Q203 reduced the number of live M. tuberculosis cells in a dose-dependent manner. This orally active small molecule blocks M. tuberculosis growth by inhibiting the cytochrome bc1 complex, which consequently inhibits the synthesis of ATP. Here, we studied the interaction profiles of Q203 with several antituberculosis drugs or drug candidates (specifically, bedaquiline, PBTZ169, PA-824, OPC-67683, SQ109, isoniazid, rifampin, streptomycin, and linezolid) using the checkerboard method, based on resazurin microtiter assays (REMAs). In the assay, none of the interactions between Q203 and the tested drugs were antagonistic, and most of the interactions were additive. However, the interaction between Q203 and PBTZ169 was synergistic, with a fractional inhibitory concentration index of 0.5. Furthermore, Q203 (one-half the MIC50) and PBTZ169 (one-half the MIC50) inhibited more bacterial growth on an agar plate compared to the dimethyl sulfoxide (DMSO) control. This synergistic effect was no longer effective when the Q203-PBTZ169 combination was tested against an M. tuberculosis mutant containing a T313A mutation causing resistance to Q203, suggesting that QcrB inhibition is integral to the Q203-PBTZ169 interaction. Thus, this synergy is not an off-target mechanism. Zebrafish (Danio rerio)-Mycobacterium marinum infection and a curing model further validated the synergistic effect of Q203 and PBTZ169 in vivo. In this study, the synergy between these two new antituberculosis drugs, Q203 and PBTZ169, is an important finding that could lead to the development of a new TB regimen.

High-Resolution Environmentally Extended Input-Output Model to Assess the Greenhouse Gas Impact of Electronics in South Korea.

South Korea is a global leader in electronics, but little is known about their climate change impact. Here, we estimate the direct and indirect greenhouse gas (GHG) emissions of Korean electronics by developing a new and high-resolution (∼380 sectors) environmentally extended input-output model, named KREEIO. We find that final demand for Korean electronics led to nearly 8% of national GHG emissions in 2017, mostly because of indirect emissions embodied in the electronics supply chain. Notably, the semiconductor and display sectors contributed 3.2% and 2.4% to national emissions, with capital investment accounting for 17% of the two sectors' total emissions or nearly 1% of national emissions. For other electronic products, scope 1, scope 2, and upstream scope 3 emissions on average accounted for 3%, 10%, and 87% of a sector's GHG intensity, respectively. Detailed contribution analysis suggests that reducing Korean electronics GHG emissions would benefit most from the transition to a low-carbon electricity grid, but mitigation efforts in many other sectors such as metals and chemicals are also important. Overall, our study underscores the significance of electronics GHG emissions in South Korea, especially those from semiconductors and displays, and the mitigation challenges these sectors face as demand continues to grow globally.

Shift to a Younger Age and Regional Differences in Inflammatory Bowel Disease in Korea: Using Healthcare Administrative Data.

BACKGROUND: Research using healthcare administrative data with a validated algorithm can reveal the real-world data of rare diseases. AIMS: We investigated an accurate algorithm for detecting incident cases of inflammatory bowel disease (IBD) from healthcare data and analyzed the nationwide population-based epidemiological features in Korea. METHODS: Healthcare data from Songpa-Kangdong districts in Seoul were extracted from the National Health Insurance Service and analyzed to identify the best algorithm reflecting the cohort data. The most accurate criterion was applied to the entire database for further analysis. RESULTS: With the selected working criteria, 37,555 incident cases of IBD (Crohn's Disease [CD], 13,130; ulcerative colitis [UC], 24,425) were identified from 2005 to 2016. The male-to-female ratio was 2.5:1 for CD and 1.4:1 for UC. Over 12 years, the annual standardized incidence rate (SIR) per 100,000 people increased from 1.6 to 2.7 and 3.8 to 4.3 for CD and UC, respectively. The peak age at diagnosis of UC shifted from 55-59 years to 20-24 years, whereas that of CD shifted from 19 to 17 years. The SIR of CD was higher in metropolitan areas than in non-metropolitan areas. CONCLUSIONS: This nationwide population-based epidemiologic study of Korean IBD revealed a gradual increase in the incidence rates and a notable shift toward younger age at diagnosis. Males were predominant in both CD and UC. There was an urban-rural difference in the SIR of CD.