The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

Peptide transporter2 (PTR2) enhances water uptake during early seed germination in Arabidopsis thaliana.

KEY MESSAGE: PTR2 in Arabidopsis thaliana is negatively regulated by ABI4 and plays a key role in water uptake by seeds, ensuring that imbibed seeds proceed to germination. Peptide transporters (PTRs) transport nitrogen-containing substrates in a proton-dependent manner. Among the six PTRs in Arabidopsis thaliana, the physiological role of the tonoplast-localized, seed embryo abundant PTR2 is unknown. In the present study, a molecular physiological analysis of PTR2 was conducted using ptr2 mutants and PTR2CO complementation lines. Compared with the wild type, the ptr2 mutant showed ca. 6 h delay in testa rupture and consequently endosperm rupture because of 17% lower water content and 10% higher free abscisic acid (ABA) content. Constitutive overexpression of the PTR2 gene under the control of the Cauliflower mosaic virus (CaMV) 35S promoter in ptr2 mutants rescued the mutant phenotypes. After cold stratification, a transient increase in ABA INSENSITIVE4 (ABI4) transcript levels during induction of testa rupture was followed by a similar increase in PTR2 transcript levels, which peaked prior to endosperm rupture. The PTR2 promoter region containing multiple CCAC motifs was recognized by ABI4 in electrophoretic mobility shift assays, and PTR2 expression was repressed by 67% in ABI4 overexpression lines compared with the wild type, suggesting that PTR2 is an immediate downstream target of ABI4. Taken together, the results suggest that ABI4-dependent temporal regulation of PTR2 expression may influence water status during seed germination to promote the post-germinative growth of imbibed seeds.

Influence of physicochemical characteristics of flour on pancake quality attributes.

This study was conducted to identify the influence of flour characteristics of 13 Korean wheat cultivars on quality attributes of pancake. Pancake diameter showed negative correlation with SRC with distilled water and pancake height and positive correlation with springiness of cooked pancake. Springiness of baked pancake was under negative correlation with protein content, SDSS, dry gluten content, and positive correlation with final viscosity and setback in pasting properties of flour. Springiness and cohesiveness of baked pancake were under negative correlation with mixing time of Mixograph. Hardness of baked pancake was correlated with amylose content and breakdown of flour. Regression and principal component analysis indicated that pancake diameter, and springiness and cohesiveness of baked pancake can be explained by protein quantity and quality parameters, protein content, SDSS, mixing time of Mixograph, and SRCs related to protein content. Hardness of baked pancake can be predicted from amylose content and breakdown of flour. Batter viscosity as well as texture of cooked pancake could be influenced by protein quality and quantity according to grain hardness.

Proteome characterization of copper stress responses in the roots of sorghum.

Copper (Cu) is a important micronutrient for plants, but it is extremely toxic to plants at high concentration and can inactivate and disturb protein structures. To explore the Cu stress-induced tolerance mechanism, the present study was conducted on the roots of sorghum seedlings exposed to 50 and 100 µM CuSO4 for 5 days. Accumulation of Cu increased in roots when the seedlings were treated with the highest concentration of Cu2+ ions (100 µM). Elevated Cu concentration provoked notable reduction of Fe, Zn, Ca, and Mn uptake in the roots of sorghum seedlings. In the proteome analysis, high-throughput two-dimensional polyacrylamide gel electrophoresis combined with MALDI-TOF-TOF MS was performed to explore the molecular responses of Cu-induced sorghum seedling roots. In two-dimensional silver-stained gels, 422 protein spots were identified in the 2-D gel whereas twenty-one protein spots (≥1.5-fold) were used to analyze mass spectrometry from Cu-induced sorghum roots. Among the 21 differentially expressed proteins, 10 proteins were increased, while 11 proteins were decreased due to the intake of Cu ions by roots of sorghum. Abundance of most of the identified proteins from the roots that function in stress response and metabolism was remarkably enhanced, while proteins involved in transcription and regulation were severely reduced. Taken together, these results imply insights into a potential molecular mechanism towards Cu stress in C4 plant, sorghum.

Prescription Trends of Psychotropics in Children and Adolescents with Autism Based on Nationwide Health Insurance Data.

Children with autism are often medicated to manage emotional and behavioral symptoms; yet, data on such pharmacotherapy is insufficient. In this study, we investigated the Korean National Health Insurance Claims Database (NHICD) information related to autism incidence and psychotropic medication use. From the 2010-2012 NHICD, we selected a total of 31,919,732 subjects under 19 years old. To examine the diagnostic incidence, we selected patients who had at least one medical claim containing an 10th revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) code for pervasive developmental disorder, F84, not diagnosed in the previous 360 days. Psychotropics were categorized into seven classes. Then, we analyzed the data to determine the mean annual diagnostic incidence and psychotropic prescription trends. Diagnostic incidence was 17,606 for the 3 years, with a mean annual incidence per 10,000 population of 5.52. Among them, 5,348 patients were prescribed psychotropics. Atypical antipsychotics were the most commonly used, followed by antidepressants. An older age, male sex, and the availability of medical aid were associated with a higher rate of prescription than observed for a younger age, female sex, and the availability of health insurance. Psychotropic drugs were used for less than one-third of patients newly diagnosed with autism, and prescription differed by sex and age. Increased diagnostic incidence is associated with an increased prescription of psychotropic drugs. Therefore, medication-related safety data and policies for psychotropic drugs in autism should be prepared.

Chromosome aberrations induced by zebularine in triticale.

Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 µmol/L) for 24 h, and the 500 µmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

Leaf proteome characterization in the context of physiological and morphological changes in response to copper stress in sorghum.

Copper (Cu) is an essential micronutrient required for normal growth and development of plants; however, at elevated concentrations in soil, copper is also generally considered to be one of the most toxic metals to plant cells due to its inhibitory effects against many physiological and biochemical processes. In spite of its potential physiological and economical significance, molecular mechanisms under Cu stress has so far been grossly overlooked in sorghum. To explore the molecular alterations that occur in response to copper stress, the present study was performed in ten-day-old Cu-exposed leaves of sorghum seedlings. The growth characteristics were markedly inhibited, and ionic alterations were prominently observed in the leaves when the seedlings were exposed to different concentrations (0, 100, and 150 µM) of CuSO4. Using two-dimensional gels with silver staining, 643 differentially expressed protein spots (≥1.5-fold) were identified as either significantly increased or reduced in abundance. Of these spots, a total of 24 protein spots (≥1.5-fold) from Cu-exposed sorghum leaves were successfully analyzed by MALDI-TOF-TOF mass spectrometry. Of the 24 differentially expressed proteins from Cu-exposed sorghum leaves, 13 proteins were up-regulated, and 11 proteins were down-regulated. The abundance of most identified protein species, which function in carbohydrate metabolism, stress defense and protein translation, was significantly enhanced, while that of another protein species involved in energy metabolism, photosynthesis and growth and development were severely reduced. The resulting differences in protein expression patterns together with related morpho-physiological processes suggested that these results could help to elucidate plant adaptation to Cu stress and provide insights into the molecular mechanisms of Cu responses in C4 plants.

Proteome analysis of roots of wheat seedlings under aluminum stress.

The root apex is considered the first sites of aluminum (Al) toxicity and the reduction in root biomass leads to poor uptake of water and nutrients. Aluminum is considered the most limiting factor for plant productivity in acidic soils. Aluminum is a light metal that makes up 7 % of the earth's scab dissolving ionic forms. The inhibition of root growth is recognized as the primary effect of Al toxicity. Seeds of wheat cv. Keumkang were germinated on petridish for 5 days and then transferred hydroponic apparatus which was treated without or with 100 and 150 µM AlCl3 for 5 days. The length of roots, shoots and fresh weight of wheat seedlings were decreased under aluminum stress. The concentration of K(+), Mg(2+) and Ca(2+) were decreased, whereas Al(3+) and P2O5 (-) concentration was increased under aluminum stress. Using confocal microscopy, the fluorescence intensity of aluminum increased with morin staining. A proteome analysis was performed to identify proteins, which are responsible to aluminum stress in wheat roots. Proteins were extracted from roots and separated by 2-DE. A total of 47 protein spots were changed under Al stress. Nineteen proteins were significantly increased such as sadenosylmethionine, oxalate oxidase, malate dehydrogenase, cysteine synthase, ascorbate peroxidase and/or, 28 protein spots were significantly decreased such as heat shock protein 70, O-methytransferase 4, enolase, and amylogenin. Our results highlight the importance and identification of stress and defense responsive proteins with morphological and physiological state under Al stress.

Profiling of mitochondrial proteome in wheat roots.

Mitochondria are important organelles for cellular respiration within the eukaryotic cell and have many important functions including vitamin synthesis, amino acid metabolism and photorespiration. To investigate the mitochondrial proteome of the roots of wheat seedlings, a systematic and targeted analysis were carried out on the mitochondrial proteome from 15 day-old wheat seedling root material. Mitochondria were isolated by Percoll gradient centrifugation; and extracted proteins were disassociated and analyzed by Tricine SDS-PAGE couple to LTQ-FTICR mass spectrometry. From the isolated the sample, 184 proteins were identified which is composed of 140 proteins as mitochondria and 44 proteins as other subcellular proteins that are predicted by the freeware sub-cellular predictor. The identified proteins in mitochondria were functionally classified into 12 classes using the ProtFun 2.2 servers based on biological processes. Proteins were shown to be involved in amino acid biosynthesis (17.1%), biosynthesis of cofactors (6.4%), cell envelope (11.4%), central intermediary metabolism (10%), energy metabolism (20%), fatty acid metabolism (0.7%), purines and pyrimidines (5.7%), regulatory functions (0.7%), replication and transcription (1.4%), translation (22.1%), transport and binding (1.4%), and unknown (2.8%). These results indicate that many of the protein components present and functions of identifying proteins are common to other profiles of mitochondrial proteins performed to date. These results are provided the extensive and noble clues, to our knowledge, of mitochondrial proteins from wheat roots.

Coupling of spin and angular momentum of light in plasmonic vortex.

We present that two distinct optical properties of light, the spin angular momentum (SAM) and the orbital angular momentum (OAM), can be coupled in the plasmonic vortex. If a plasmonic vortex lens (PVL) is illuminated by the helical vector beam (HVB) with the SAM and OAM, then those distinct angular momenta contribute to the generation of the plasmonic vortex together. The analytical model reveals that the total topological charge of the generated plasmonic vortex is given by a linear summation of those of the SAM and OAM, as well as the geometric charge of the PVL. The generation of the plasmonic vortex and the manipulation of the fractional topological charge are also presented.

Changes in physiology and protein abundance in salt-stressed wheat chloroplasts.

Leaves are the final site of salinity perception through the roots. To better understand how wheat chloroplasts proteins respond to salt stress, the study aimed to the physiochemical and comparative proteomics analysis. Seedlings (12-days-old) were exposed to 150 mM NaCl for 1, 2, or 3 days. Na(+) ions were rapid and excessively increase in roots, stems and leaves. Photosynthesis and transpiration rate, stomatal conductance, and relative water content decreased whereas the level of proline increased. Statistically significant positive correlations were found among the content of hydrogen peroxide, activity of catalase, and superoxide dismutase under salt stress in wheat. Protein abundance within the chloroplasts was examined by two-dimensional electrophoresis. More than 100 protein spots were reproducibly detected on each gel, 21 protein spots were differentially expressed during salt treatment. Using linear quadruple trap-Fourier transform ion cyclotron resonance (LTQ-FTICR) hybrid mass spectrometry, 65 unique proteins assigned in the differentially abundant spots. Most proteins were up-regulated at 2 and 3 days after being down-regulated at 1 day. Others showed only slight responses after 3 days of treatment, including Rubisco, glutamate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, isocitrate dehydrogenase, photosystem I, and pyridoxal biosynthesis protein PDX1.2 and PDX1.3. The ATP synthase (α, ß, and γ) and V-type proton ATPase subunits were down-regulated resulting showed negative impact by Na(+) on the photosynthetic machinery. This ephemeral increase and subsequent decrease in protein contents may demonstrate a counterbalancing influence of identified proteins. Several proteins such as cytochrome b6-f (Cyt b6-f), germin-like-protein, the γ-subunit of ATP synthase, glutamine synthetase, fructose-bisphosphate aldolase, S-adenosylmethionine synthase, carbonic anhydrase were gradually up-regulated during the period of treatment, which can be identified as marker proteins.

Generation of multiple vortex-cones by direct-phase modulation of annular aperture array.

The generation of multiple vortex cones using an annular aperture array and a spatial light modulator (SLM) is studied. The direct downscale imaging of an SLM on the surface of an annular aperture enables the direct-phase modulation of the annular aperture. It is experimentally demonstrated that the direct-phase modulation of an annular aperture array can control both the topological charge and the horizontal positions of multiple vortex cones simultaneously.

Clinical implication of interstitial lung abnormality in elderly patients with early-stage non-small cell lung cancer.

BACKGROUND: Interstitial lung abnormality (ILA) is closely related to lung cancer. This study aimed to assess whether the presence of ILA is associated with the clinicoradiological features of elderly patients (≥70 years) with early-stage non-small cell lung cancer (NSCLC). METHODS: Elderly patients who underwent surgical resection for stage I or II NSCLC with preserved lung function between 2012 and 2019 were retrospectively identified. ILA was evaluated using a three-point scale. Univariate analyses were performed for clinicoradiological features based on the presence of ILA. Logistic and linear regression analyses were performed for cancer staging and tumor size, respectively. RESULTS: A total of 254 patients were evaluated. The presence of ILA (score = 2) was significantly associated with male sex, current or former smoker status, higher pack-years of smoking, low forced expiratory volume in one second/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide, and presence of emphysema (≥5%). Tumor characteristics, such as lower lobe and outer one-third location, squamous cell carcinoma, and higher cancer stage (stage II) were significantly associated with ILA. The presence of ILA independently predicted a higher cancer stage (adjusted odds ratio, 1.81; 95% confidence interval, 1.10-2.96; p = 0.02) and a larger tumor size in linear regression analysis (p = 0.04). CONCLUSIONS: Patients with ILA showed clinicoradiological features similar to those of idiopathic pulmonary fibrosis in elderly patients with early-stage NSCLC. Identifying the clinical implications of ILA in early-stage lung cancer will guide clinicians in providing appropriate management for these patients.

Synthesis and dynamic switching of surface plasmon vortices with plasmonic vortex lens.

The generation of surface plasmon vortices with arbitrary higher order vortex topological charges with novel plasmonic vortex lens is experimentally demonstrated. It is shown that the polarization sensitivity of the plasmonic vortex lens can be utilized for the dynamic switching of the surface plasmon vortices with different topological charges. A simple algebraic rule related to the vortex topological charge change in the dynamic switching is formulated, and its proof is provided with theory and experiment. The synthesis and dynamic switching of higher order surface plasmon vortices have profound potential in optical trapping, optical data storage, and other related fields.

Phase-shifting interferometry with genetic algorithm-based twin image noise elimination.

Phase-shifting interferometry with a genetic algorithm is proposed. The correction of unknown phase-shifting error is an important task in general phase-shifting interferometry. Since phase-shifting errors generate twin image noise in a reconstructed image, we can reduce the phase-shifting errors indirectly by trying to eliminate the twin-image noise in the reconstructed image. By Zernike polynomial expansion, the reconstructed image is represented as the evenness and oddness, where the ratio of the evenness and oddness is a measure of the amount of the twin image noise. We employ the genetic algorithm for finding the fittest phase shifts of interferograms by reducing the evenness of the reconstructed image, which leads to reduction of phase-shifting errors. This phase-shifting interferometry with a genetic algorithm is confirmed experimentally.

Novel molecular marker-assisted strategy for production of wheat-Leymus mollis chromosome addition lines.

Developing wheat-alien chromosome introgression lines to improve bread wheat's resistance to stresses, such as drought, salinity stress and diseases, requires reliable markers to identify and characterize the alien chromatins. Leymus mollis is a wild relative of bread wheat resistant to salinity and economically important diseases of wheat, but its genome sequence and cytological markers are not available. We devised a molecular marker-assisted strategy for L. mollis chromosome identification and applied it to produce 10 wheat-L. mollis chromosome addition lines. Using 47 L. racemosus genome polymorphic PCR markers and DArTseq genotyping, we distinguished the L. mollis chromosomes and differentiated disomic and monosomic lines by progeny test. DArTseq genotyping generated 14,530 L. mollis SNP markers and the chromosome-specific SNP markers were used to determine the homoeologous groups of L. mollis chromosomes in the addition lines. To validate the marker-based results, genomic in situ hybridization was applied to confirm the presence and cytological status of L. mollis chromosomes in the lines. This study demonstrates that adequate molecular markers allow the production and characterization of wheat-alien addition lines without in situ hybridization, which saves considerable time and effort.

Burr Hole Drainage with Urokinase Irrigation for the Treatment of Acute Subdural Hematoma: A Case Report.

We describe the case of a patient with an acute subdural hematoma (SDH) that was removed using urokinase irrigation after burr hole trephination in a limited situation where craniotomy was not possible. A 90-year-old woman was admitted to our hospital with a stuporous mental status. Computed tomography (CT) scans revealed a chronic SDH, and a burr hole procedure was performed. The patient's postoperative progression was good until the third day after surgery when we found that the acute SDH had increased on CT scans. The patient's guardian refused further surgery, and thus we drained the blood from the hematoma by injecting urokinase through a drainage catheter. We used urokinase for two days, and removed the catheter after confirming via CT scans that the hematoma was almost alleviated. The patient recovered gradually; she was discharged with few neurological deficits.

Incidence and Comorbidity of Reactive Attachment Disorder: Based on National Health Insurance Claims Data, 2010-2012 in Korea.

OBJECTIVE: We aimed to investigate the current diagnostic incidence, and medical and psychiatric comorbidities of reactive attachment disorder (RAD) using the National Health Insurance Review and Assessment (HIRA) claims data. METHODS: To examine the diagnostic incidence, we selected patients who were under 10-year-old and who had at least one medical claim containing a 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) code for RAD (F94.1 and F94.2) and who had not been diagnosed in the previous 360 days, from 2010 to 2012. In this study, we used the term 'reactive attachment disorder' representing for both RAD per se and Disinhibited social engagement disorder. Comorbid disorders were categorized according to ICD-10. RESULTS: Among 14,029,571, the total population under 10-year-old during 2010-2012, incident cases of RAD were 736. The mean diagnostic incidence of RAD was 5.25 per 100,000 annually. Language disorders (F80-84) were the most common psychiatric comorbidities in both boys and girls in age groups 0-3 years and 4-6 years, and attention deficit hyperactivity disorder was the most common in both sex aged 7-9 years. In non-psychiatric comorbidities, diseases of the respiratory system (J00-99) were the commonest in both sex in all age groups, and diseases of the digestive system (K00-99) were the next. CONCLUSION: RAD was very rare in practice and would be disguised as other psychiatric disorders. Children with RAD might have more medical comorbidities than typically developed children.

Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model.

Vascular networks are the first sites exposed to cationic polymer nanoparticles (NPs) administered intravenously, and thus function as a barrier for NPs reaching the target organ. While cationic polymer NPs have been intensively studied as non-viral delivery systems, their biological effects in human microvessels have been poorly investigated due to a lack of appropriate in vitro systems. Here, we employed a three-dimensional microvessel on a chip, which accurately models in vivo conditions. An open and perfused microvessel surrounded by pericytes was shown to reproduce the important features of living vasculature, including barrier function and biomarkers. Using this microvessel chip, we observed contraction of the microvascular lumen induced by perfused polyethylenimine (PEI)/DNA NPs. We demonstrated that the oxidative stress present when microvessels were exposed to PEI NPs led to rearrangement of microtubules resulting in microvessel contraction. Furthermore, the transcytotic behavior of PEI NPs was analyzed in the microvessel by monitoring the escape of PEI NPs from the microvascular lumen into the perivascular region, which was not possible in two-dimensional culture systems. With our new understanding of the different behaviors of cationic polymer NPs depending on their transcytotic route, we suggest that caveolae-mediated transcytosis is a powerful route for efficient extravascular transport. STATEMENT OF SIGNIFICANCE: Microvascular networks are not only biological system constituting largest surface area in the body and but also first site exposed to nanoparticle in vivo. While cationic polymer NPs have been intensively studied as non-viral delivery systems, its biological effects in human microvessel have been poorly investigated due to lack of appropriate in vitro systems. Here, we microengineered an open and perfused 3D pericyte incorporated microvessel model which possesses same morphological characteristic of in vivo. Using the microengineered model, this study represents the first report of transcytotic behavior of NPs in 3D microvessel, and its effect on extravasation efficiency. Our study lays the groundwork for the integration of innovative technologies to examine blood vessel-nanoparticle interaction, which a critical but ill-defined phenomenon.

A thin 3D-2D convertible integral imaging system using a pinhole array on a polarizer.

A three-dimension(3D)/two-dimension(2D) convertible display system is proposed. The proposed system realizes a thin structure by adopting a pinhole array to generate point light sources for 3D display mode from a backlight source. The optical efficiency of 2D display mode is also enhanced using polarization control. By experiments, the proposed method was proven and compared with a previous one.