Molecular incompatibility between pig CD200 and human CD200 receptor in in vitro xenogeneic immune responses.

Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1ß, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200.

Bottom-Up Evolution of Diamond-Graphite Hybrid Two-Dimensional Nanostructure: Underlying Picture and Electrochemical Activity.

The diamond-graphite hybrid thin film with low-dimensional nanostructure (e.g., nitrogen-included ultrananocrystalline diamond (N-UNCD) or the alike), has been employed in many impactful breakthrough applications. However, the detailed picture behind the bottom-up evolution of such intriguing carbon nanostructure is far from clarified yet. Here, the authors clarify it, through the concerted efforts of microscopic, physical, and electrochemical analyses for a series of samples synthesized by hot-filament chemical vapor deposition using methane-hydrogen precursor gas, based on the hydrogen-dependent surface reconstruction of nanodiamond and on the substrate-temperature-dependent variation of the growth species (atomic hydrogen and methyl radical) concentration near substrate. The clarified picture provides insights for a drastic enhancement in the electrochemical activities of the hybrid thin film, concerning the detection of important biomolecule, that is, ascorbic acid, uric acid, and dopamine: their limits of detections are 490, 35, and 25 nm, respectively, which are among the best of the all-carbon thin film electrodes in the literature. This work also enables a simple and effective way of strongly enhancing AA detection.

Antiallergic Effects of N,N-dicoumaroylspermidine Isolated from Lithospermum erythrorhizon on Mast Cells and Ovalbumin-Induced Allergic Rhinitis.

In East Asia, the dried root of Lithospermum erythrorhizon has been utilized as an anti-inflammatory, antipyretic, detoxifying, and anti-inflammatory agent. Recently, we reported that L. erythrorhizon protects against allergic rhinitis; however, the component within L. erythrorhizon that exerts antiallergic activity remains unknown. The purpose of the current study was to isolate and characterize the antiallergic active components in an ethanolic extract of L. erythrorhizon roots. We examined the antiallergic effects of L. erythrorhizon reflux ethanol extracts in an ovalbumin (OVA)-induced allergic rhinitis mouse model, and compared the chemical compounds extracted using the hot reflux and cold extraction methods. Chromatographic separation identified two novel anthraquinones, erythrin A and B, one newly discovered compound from the Lithospermum genus, N1″,N3″-dicoumaroylspermidine, and nineteen other recognized compounds. Their chemical structures were elucidated by single (1D) and 2D analysis of nuclear magnetic resonance (NMR) spectroscopic data, as well as high resolution mass spectrometry. Among the identified compounds, N,N'-dicoumaroylspermidine strongly inhibited the release of ß-hexosaminidase, as well as the production of IL-3, IL-4, and IL-13 by IgE-sensitized and BSA-stimulated RBL-2H3 cells. Using the OVA-induced allergic rhinitis mouse model, we showed that N,N'-dicoumaroylspermidine reduced the production of serum OVA-specific IgE and the number of inflammatory cells in nasal lavage fluid. N,N'-dicoumaroylspermidine isolated from L. erythrorhizon exhibits antiallergic properties, making it potentially effective for allergic rhinitis.

Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration.

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Stabilization of the Triplet Biradical Intermediate of 5-Methylcytosine Enhances Cyclobutane Pyrimidine Dimer (CPD) Formation in DNA.

Cyclobutane pyrimidine dimer (CPD) is a photoproduct formed by two stacked pyrimidine bases through a cycloaddition reaction upon irradiation. Owing to its close association with skin cancer, the mechanism of CPD formation has been studied thoroughly. Among many aspects of CPD, its formation involving 5-methylcytosine (5mC) has been of special interest because the CPD yield is known to increase with C5-methylation of cytosine. In this work, high-level quantum mechanics/molecular mechanics (QM/MM) calculations are used to examine a previously experimentally detected pathway for CPD formation in hetero (thymine-cytosine and thymine-5mC) dipyrimidines, which is facilitated through intersystem crossing in thymine and formation of a triplet biradical intermediate. A DNA duplex model system containing a core sequence TmCG or TCG is used. The stabilization of a radical center in the biradical intermediate by the methyl group of 5mC can lead to increased CPD yield in TmCG compared with its non-methylated counterpart, TCG, thereby suggesting the existence of a new pathway of CPD formation enhanced by 5mC.

Surveillance of Chigger Mite Vectors for Tsutsugamushi Disease in the Hwaseong Area, Gyeonggi-do, Republic of Korea, 2015.

Owing to global climate change, the global resurgence of vector-borne infectious diseases and their potential to inflict widespread casualties among human populations has emerged as a pivotal burden on public health systems. Tsutsugamushi disease (scrub typhus) in the Republic of Korea is steadily increasing and was designated as a legal communicable disease in 1994. The disease is a mite-borne acute febrile disease most commonly contracted from October to December. In this study, we tried to determine the prevalence of tsutsugamushi disease transmitted by chigger mites living on rodents and investigated their target vector diversity, abundance, and distribution to enable the mapping of hotspots for this disease in 2015. A total of 5 species belonging to 4 genera (109 mites): Leptotrombidium scutellare 60.6%, L. pallidum 28.4% Neotrombicula tamiyai 9.2%, Euschoengastia koreaensis/0.9%), and Neoschoengastia asakawa 0.9% were collected using chigger mite collecting traps mimicking human skin odor and sticky chigger traps from April to November 2015. Chigger mites causing tsutsugamushi disease in wild rodents were also collected in Hwaseong for the zoonotic surveillance of the vector. A total of 77 rodents belonging to 3 genera: Apodemus agrarius (93.5%), Crocidura lasiura (5.2%), and Micromys minutus (1.3%) were collected in April, October, and November 2015. The most common mite was L. pallidum (46.9%), followed by L. scutellare (18.6%), and L. orientale (18.0%). However, any of the chigger mite pools collected from rodent hosts was tested positive for Orientia tsutsugamushi, the pathogen of tsutsugamushi disease, in this survey.

Role of charge transfer states into the formation of cyclobutane pyrimidine dimers in DNA.

Photoinduced charge transfer between neighboring bases plays an important role in DNA. One of its important effects is shown in its ability to affect the photochemical yields of the formation of cyclobutane pyrimidine dimer (CPD) products between adjacent pyrimidine bases. In this work we examine how the energies of charge transfer states depend on the sequences of oligonucleotides using a hybrid quantum and molecular mechanics (QM/MM) methodology combined with the algebraic diagrammatic construction through a second order electronic structure method for excited states. Specifically, we examine 10 sequences with guanine being on the 5' or 3' position of two pyrimidine bases. The results show that the energies of charge transfer states are affected by the nature of the donor acceptor pair, by the distance between them, and by other electrostatic effects created by the surrounding environment.

Four Year Surveillance of the Vector Hard Ticks for SFTS, Ganghwa-do, Republic of Korea.

The seasonal abundance of hard ticks that transmit severe fever with thrombocytopenia syndrome virus was monitored with a collection trap method every April to November during 2015-2018 and with a flagging method every July and August during 2015-2018 in Ganghwa-do (island) of Incheon Metropolitan City, Republic of Korea. This monitoring was performed in a copse, a short grass field, coniferous forest and broad-leaved forest. A total of 17,457 ticks (8,277 larvae, 4,137 nymphs, 3,389 females, and 1,654 males) of the ixodid ticks comprising 3 species (Haemaphysalis longicornis, H. flava, and Ixodes nipponensis) were collected with collection traps. Of the identified ticks, H. longicornis was the most frequently collected ticks (except larval ticks) (94.26%, 8,653/9,180 ticks (nymphs and adults)), followed by H. flava (5.71%, 524/9,180) and Ix. nipponensis (less than 0.04%, 3/9,180). The ticks collected with collecting traps were pooled and assayed for the presence of SFTS virus with negative results. In addition, for monitoring the prevalence of hard ticks, a total of 7,461 ticks (5,529 larvae, 1,272 nymphs, 469 females, and 191 males) of the ixodid ticks comprising 3 species (H. longicornis, H. flava, and Ix. nipponensis) were collected with flagging method. H. longicornis was the highest collected ticks (except larval ticks) (99.53%, 1,908/1,917 ticks (nymphs and adults)), followed by H. flava (1.15%, 22/1,917).

Photochemical Formation of Cyclobutane Pyrimidine Dimers in DNA through Electron Transfer from a Flanking Base.

Electron transfer (ET) to a pyrimidine base from external moieties is a common step involved in the quenching or repair of the cyclobutane pyrimidine dimer (CPD). In contrast, we present a pathway that is initiated by an ET from a flanking guanine base to a pyrimidine base, leading to the formation of a CPD. We studied a T5mCG sequence with a methylated cytosine and our results demonstrate that the pathway involves the formation of an exciplex and intersystem crossings. This pathway also provides an explanation for why the mutational hot spots are correlated with the methylated CpG sequences, which has been a significant issue in cancer research.

A proton transfer network that generates deprotonated tyrosine is a key to producing reactive oxygen species in phototoxic KillerRed protein.

KillerRed is the first genetically encoded photosensitizer that can induce cytotoxicity upon light exposure. Nevertheless, its phototoxicity is still lower than that of chemical photosensitizers, and the efforts to further develop KillerRed variants with enhanced phototoxicity have been impeded because the mechanism by which it generates cytotoxic reactive oxygen species (ROS) has remained elusive. To shed light on this issue, we employ quantum mechanics/molecular mechanics (QM/MM) modeling with statistical free energy analysis to examine the photo-induced electron transfer reaction occurring in KillerRed. We identify a deprotonated tyrosine residue (Tyr110) as an electron donor and further show that adjacent glutamate and serine residues play essential roles in deprotonating Tyr110. We also show that water mediation is important in the proton transfer and that protein fluctuations importantly govern the fate of the excited system. We provide clues about why KillerRed can only exhibit a low ROS yield and suggest future directions of mutagenesis toward an enhanced phototoxicity.

Uliginosibacterium sangjuense sp. nov., isolated from sediment of the Nakdong River.

A Gram-negative, aerobic, motile by flagella, and light yellow bacterium, designated SS1-76T, was isolated from sediment of the Nakdong River in Sangju-si, Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate SS1-76T belongs to the genus Uliginosibacterium of the family Rhodocyclaceae, exhibiting high sequence similarity with the type strains of Uliginosibacterium gangwonense 5YN10-9T (96.0%) and Uliginosibacterium paludis KBP-13T (94.9%). Strain SS1-76T contains ubiquinone-8 as a respiratory quinone and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0, and C14:0 as major fatty acids. The cellular polar lipids are composed of phosphatidylethanolamine, phosphatidylglycerol, and unidentified aminophospholipids. The DNA G+C content was 65.3 mol%. Phenotypic, chemotaxonomic, and phylogenetic evidence clearly indicated that strain SS1-76T represents a novel species of the genus Uliginosibacterium, for which the name Uliginosibacterium sangjuense sp. nov. is proposed. The type strain is SS1-76T (= KCTC 52159T = JCM 31375T).

Telecom-Wavelength Bottom-up Nanobeam Lasers on Silicon-on-Insulator.

Semiconductor nanowire lasers are considered promising ultracompact and energy-efficient light sources in the field of nanophotonics. Although the integration of nanowire lasers onto silicon photonic platforms is an innovative path toward chip-scale optical communications and photonic integrated circuits, operating nanowire lasers at telecom-wavelengths remains challenging. Here, we report on InGaAs nanowire array lasers on a silicon-on-insulator platform operating up to 1440 nm at room temperature. Bottom-up photonic crystal nanobeam cavities are formed by growing nanowires as ordered arrays using selective-area epitaxy, and single-mode lasing by optical pumping is demonstrated. We also show that arrays of nanobeam lasers with individually tunable wavelengths can be integrated on a single chip by the simple adjustment of the lithographically defined growth pattern. These results exemplify a practical approach toward nanowire lasers for silicon photonics.

Monolithic InGaAs Nanowire Array Lasers on Silicon-on-Insulator Operating at Room Temperature.

Chip-scale integrated light sources are a crucial component in a broad range of photonics applications. III-V semiconductor nanowire emitters have gained attention as a fascinating approach due to their superior material properties, extremely compact size, and capability to grow directly on lattice-mismatched silicon substrates. Although there have been remarkable advances in nanowire-based emitters, their practical applications are still in the early stages due to the difficulties in integrating nanowire emitters with photonic integrated circuits. Here, we demonstrate for the first time optically pumped III-V nanowire array lasers monolithically integrated on silicon-on-insulator (SOI) platform. Selective-area growth of InGaAs/InGaP core/shell nanowires on an SOI substrate enables the nanowire array to form a photonic crystal nanobeam cavity with superior optical and structural properties, resulting in the laser to operate at room temperature. We also show that the nanowire array lasers are effectively coupled with SOI waveguides by employing nanoepitaxy on a prepatterned SOI platform. These results represent a new platform for ultracompact and energy-efficient optical links and unambiguously point the way toward practical and functional nanowire lasers.

Macrophage C-type lectin is essential for phagosome maturation and acidification during Escherichia coli-induced peritonitis.

Sepsis is a life-threatening condition caused by an uncontrolled response to bacterial infection. Impaired bactericidal activity in the host is directly associated with severe sepsis; however, the underlying regulatory mechanism(s) is largely unknown. Here, we show that MCL (macrophage C-type lectin) plays a crucial role in killing bacteria during Escherichia coli-induced peritonitis. MCL-deficient mice with E. coli-induced sepsis showed lower survival rates and reduced bacterial clearance when compared with control mice, despite similar levels of proinflammatory cytokine production. Although the ability of macrophages from MCL-deficient mice to kill bacteria was impaired, they showed normal phagocytic activity and production of reactive oxygen species. In addition, MCL-deficient macrophages showed defective phagosome maturation and phagosomal acidification after E. coli infection. Taken together, these results indicate that MCL plays an important role in host defense against E. coli infection by promoting phagosome maturation and acidification, thereby providing new insight into the role of MCL during pathogenesis of sepsis and offering new therapeutic options.

Mycobacterial cord factor enhances migration of neutrophil-like HL-60 cells by prolonging AKT phosphorylation.

Trehalose 6,6'-dimycolate (TDM), or cord factor, is a crucial stimulus of immune responses during Mycobacterium tuberculosis infection. Although TDM has immuno-stimulatory properties, including adjuvant activity and the ability to induce granuloma formation, the mechanisms underlying these remain unknown. We hypothesized that TDM stimulates transendothelial migration of neutrophils, which are the first immune cells to infiltrate the tissue upon infection. In this study, it was shown that TDM enhances N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis and transendothelial movement by prolonging AKT phosphorylation in human neutrophils. TDM induced expression of macrophage-inducible C-type lectin, a receptor for TDM, and induced secretion of pro-inflammatory cytokines and chemokines in differentiated HL-60 cells. In 2- and 3-D neutrophil migration assays, TDM-stimulated neutrophils showed increased fMLP-induced chemotaxis and transendothelial migration. Interestingly, following fMLP stimulation of TDM-activated neutrophils, AKT, a crucial kinase for neutrophil polarization and chemotaxis, showed prolonged phosphorylation at serine 473. Taken together, these data suggest that TDM modulates transendothelial migration of neutrophils upon mycobacterial infection through prolonged AKT phosphorylation. AKT may therefore be a promising therapeutic target for enhancing immune responses to mycobacterial infection.

Conformational and electronic effects on the formation of anti cyclobutane pyrimidine dimers in G-quadruplex structures.

Cyclobutane pyrimidine dimers (CPDs) are the most commonly formed photochemical products when nucleic acids interact with UV radiation. In duplex DNA, the relative inflexible structure allows for only the cis, syn CPD isomer to be formed. G-quadruplex structures, however, have loops that are more flexible and allow for different orientations of the bases to interact. As a result, the highly unusual formation of an anti CPD has been observed in these structures. Due to the close proximity between two opposing loops containing the TTA sequence in two G-quadruplex structures (called "form-3" and "basket"), a high yield of anti CPD formation was expected in these structures. However, while significant yields of anti CPDs are observed in form-3, the anti CPD is hardly observed in the basket structure. To account for this inconsistency, we examine the process of anti CPD formation in form-3 and basket structures using simulations at the atomistic level. Here, we consider the conformational effect using MD simulations, which show whether the formation of the anti CPD is structurally feasible. Quantum mechanical/molecular mechanical (QM/MM) calculations of excited states are also used to consider the electronic effect by an adjacent guanine base which can quench the formation of the anti CPD through charge transfer (CT). Our results are in qualitative agreement with the experimental results, predicting a significant yield of the anti CPD in the form-3 structure and a negligible yield in the basket structure, while they also predict the formation of the cis, syn CPD between two opposing loops in form-3. Most importantly, our simulation results show that the yields of the anti CPD in the G-quadruplex are affected significantly by both conformational and electronic effects.

Monolithically Integrated InGaAs Nanowires on 3D Structured Silicon-on-Insulator as a New Platform for Full Optical Links.

Monolithically integrated III-V semiconductors on a silicon-on-insulator (SOI) platform can be used as a building block for energy-efficient on-chip optical links. Epitaxial growth of III-V semiconductors on silicon, however, has been challenged by the large mismatches in lattice constants and thermal expansion coefficients between epitaxial layers and silicon substrates. Here, we demonstrate for the first time the monolithic integration of InGaAs nanowires on the SOI platform and its feasibility for photonics and optoelectronic applications. InGaAs nanowires are grown not only on a planar SOI layer but also on a 3D structured SOI layer by catalyst-free metal-organic chemical vapor deposition. The precise positioning of nanowires on 3D structures, including waveguides and gratings, reveals the versatility and practicality of the proposed platform. Photoluminescence measurements exhibit that the composition of ternary InGaAs nanowires grown on the SOI layer has wide tunability covering all telecommunication wavelengths from 1.2 to 1.8 µm. We also show that the emission from an optically pumped single nanowire is effectively coupled and transmitted through an SOI waveguide, explicitly showing that this work lays the foundation for a new platform toward energy-efficient optical links.

High Quantum Efficiency Nanopillar Photodiodes Overcoming the Diffraction Limit of Light.

InAs1-xSbx nanowires have recently attracted interest for infrared sensing applications due to the small bandgap and high thermal conductivity. However, previous reports on nanowire-based infrared sensors required low operating temperatures in order to mitigate the high dark current and have shown poor sensitivities resulting from reduced light coupling efficiency beyond the diffraction limit. Here, InAsSb nanopillar photodiodes with high quantum efficiency are achieved by partially coating the nanopillar with metal that excites localized surface plasmon resonances, leading to quantum efficiencies of ∼29% at 2390 nm. These high quantum efficiency nanopillar photodiodes, with 180 nm diameters and 1000 nm heights, allow operation at temperatures as high as 220 K and exhibit a detection wavelength up to 3000 nm, well beyond the diffraction limit. The InAsSb nanopillars are grown on low cost GaAs (111)B substrates using an InAs buffer layer, making our device architecture a promising path toward low-cost infrared focal plane arrays with high operating temperature.