Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model.

SARS-CoV-2 has become a global public health problem. Acute respiratory distress syndrome (ARDS) is the leading cause of death due to the SARS-CoV-2 infection. Pulmonary fibrosis (PF) is a severe and frequently reported COVID-19 sequela. In this study, an in vitro model of ARDS and PF caused by SARS-CoV-2 was established in MH-S, THP-1, and MRC-5 cells using pseudo-SARS-CoV-2 (PSCV). Expression of proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) and HIF-1α was increased in PSCV-infected MH-S and THP-1 cells, ARDS model, consistent with other profiling data in SARS-CoV-2-infected patients have been reported. Hypoxia-inducible factor-1 alpha (HIF-1α) siRNA and cobalt chloride were tested using this in vitro model. HIF-1α knockdown reduces inflammation caused by PSCV infection in MH-S and THP-1 cells and lowers elevated levels of CTGF, COLA1, and α-SMA in MRC-5 cells exposed to CPMSCV. Furthermore, apigetrin, a glycoside bioactive dietary flavonoid derived from several plants, including Crataegus pinnatifida, which is reported to be a HIF-1α inhibitor, was tested in this in vitro model. Apigetrin significantly reduced the increased inflammatory cytokine (IL-6, IL-1ß, and TNF-α) expression and secretion by PSCV in MH-S and THP-1 cells. Apigetrin inhibited the binding of the SARS-CoV-2 spike protein RBD to the ACE2 protein. An in vitro model of PF induced by SARS-CoV-2 was produced using a conditioned medium of THP-1 and MH-S cells that were PSCV-infected (CMPSCV) into MRC-5 cells. In a PF model, CMPSCV treatment of THP-1 and MH-S cells increased cell growth, migration, and collagen synthesis in MRC-5 cells. In contrast, apigetrin suppressed the increase in cell growth, migration, and collagen synthesis induced by CMPSCV in THP-1 and MH-S MRC-5 cells. Also, compared to control, fibrosis-related proteins (CTGF, COLA1, α-SMA, and HIF-1α) levels were over two-fold higher in CMPSV-treated MRC-5 cells. Apigetrin decreased protein levels in CMPSCV-treated MRC-5 cells. Thus, our data suggest that hypoxia-inducible factor-1 alpha (HIF-1α) might be a novel target for SARS-CoV-2 sequela therapies and apigetrin, representative of HIF-1alpha inhibitor, exerts anti-inflammatory and PF effects in PSCV-treated MH-S, THP-1, and CMPVSC-treated MRC-5 cells. These findings indicate that HIF-1α inhibition and apigetrin would have a potential value in controlling SARS-CoV-2-related diseases.

Side- and Sinus-Specific Relationships between Chronic Rhinosinusitis and Ischemic Stroke Using Imaging Analyses.

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund-Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer's V = 0.479, p < 0.001), anterior (Cramer's V = 0.396, p < 0.001)/posterior (Cramer's V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer's V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer's V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer's V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204-2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke.

Development of a double-grating differential interferometer for plasma diagnostics.

A special differential interferometer consisting of two gratings was developed for diagnostics of plasma density. Compared with other differential interferometers, our system has an important advantage that the shear distance, shear direction, and fringe width can be adjusted independently, enabling easy control of the parameters. This feature allows precise tuning of the two probe beams in the interferometer for rigorous differential phase diagnosis and more accurate information of the plasma density can be obtained. The double-grating-based differential interferometer was tested for diagnostics of the laser-produced plasma which was generated by focusing a 1 TW/35 fs Ti:sapphire laser pulse in a gas jet with a 100 µm orifice diameter. It was confirmed that our differential interferometer can provide more reliable and accurate plasma density information, especially for plasmas with a high spatial gradient in density.

Feasibility of video-based real-time nystagmus tracking: a lightweight deep learning model approach using ocular object segmentation.

Background: Eye movement tests remain significantly underutilized in emergency departments and primary healthcare units, despite their superior diagnostic sensitivity compared to neuroimaging modalities for the differential diagnosis of acute vertigo. This underutilization may be attributed to a potential lack of awareness regarding these tests and the absence of appropriate tools for detecting nystagmus. This study aimed to develop a nystagmus measurement algorithm using a lightweight deep-learning model that recognizes the ocular regions. Method: The deep learning model was used to segment the eye regions, detect blinking, and determine the pupil center. The model was trained using images extracted from video clips of a clinical battery of eye movement tests and synthesized images reproducing real eye movement scenarios using virtual reality. Each eye image was annotated with segmentation masks of the sclera, iris, and pupil, with gaze vectors of the pupil center for eye tracking. We conducted a comprehensive evaluation of model performance and its execution speeds in comparison to various alternative models using metrics that are suitable for the tasks. Results: The mean Intersection over Union values of the segmentation model ranged from 0.90 to 0.97 for different classes (sclera, iris, and pupil) across types of images (synthetic vs. real-world images). Additionally, the mean absolute error for eye tracking was 0.595 for real-world data and the F1 score for blink detection was ≥ 0.95, which indicates our model is performing at a very high level of accuracy. Execution speed was also the most rapid for ocular object segmentation under the same hardware condition as compared to alternative models. The prediction for horizontal and vertical nystagmus in real eye movement video revealed high accuracy with a strong correlation between the observed and predicted values (r = 0.9949 for horizontal and r = 0.9950 for vertical; both p < 0.05). Conclusion: The potential of our model, which can automatically segment ocular regions and track nystagmus in real time from eye movement videos, holds significant promise for emergency settings or remote intervention within the field of neurotology.

Identification of Viruses Infecting Phalaenopsis Orchids Using Nanopore Sequencing and Development of an RT-RPA-CRISPR/Cas12a for Rapid Visual Detection of Nerine Latent Virus.

Phalaenopsis orchids are one of the most popular ornamental plants. More than thirty orchid viruses have been reported, and virus-infected Phalaenopsis orchids significantly lose their commercial value. Therefore, the development of improved viral disease detection methods could be useful for quality control in orchid cultivation. In this study, we first utilized the MinION, a portable sequencing device based on Oxford Nanopore Technologies (ONT) to rapidly detect plant viruses in Phalaenopsis orchids. Nanopore sequencing revealed the presence of three plant viruses in Phalaenopsis orchids: odontoglossum ringspot virus, cymbidium mosaic virus, and nerine latent virus (NeLV). Furthermore, for the first time, we detected NeLV infection in Phalaenopsis orchids using nanopore sequencing and developed the reverse transcription-recombinase polymerase amplification (RT-RPA)-CRISPR/Cas12a method for rapid, instrument-flexible, and accurate diagnosis. The developed RT-RPA-CRISPR/Cas12a technique can confirm NeLV infection in less than 20 min and exhibits no cross-reactivity with other viruses. To determine the sensitivity of RT-RPA-CRISPR/Cas12a for NeLV, we compared it with RT-PCR using serially diluted transcripts and found a detection limit of 10 zg/µL, which is approximately 1000-fold more sensitive. Taken together, the ONT platform offers an efficient strategy for monitoring plant viral pathogens, and the RT-RPA-CRISPR/Cas12a method has great potential as a useful tool for the rapid and sensitive diagnosis of NeLV.

Total spine MRI for the preoperative evaluation of adolescent idiopathic scoliosis: part 1.

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.

Total spine MRI for the preoperative evaluation of adolescent idiopathic scoliosis: Part 2 - spinal cord tumors, dysraphisms, diastematomyelia, and vertebral anomalies.

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.

Trends in Distributions of Hearing Threshold Levels by Ages: A Comparison of the ISO 7029 and Newly Available Country-Specific Data.

Hearing thresholds provide essential information and references about the human auditory system. This study aimed to identify changing trends in distributions of hearing threshold levels across ages by comparing the International Organization for Standardization (ISO) 7029 and newly available data after publishing ISO 7029. To compare ISO 7029 and newly available hearing threshold data after publishing ISO 7029, four country-specific datasets that presented average hearing threshold levels under conditions similar to ISO 7029 were utilized. For frequencies between 125 Hz and 8,000 Hz, the deviations of hearing threshold values by ages from the hearing threshold of the youngest age group for each data point were utilized. For frequencies from 9,000 Hz to 12,500 Hz, the median threshold information was utilized. Hearing threshold data reported after publishing ISO 7029 from the four countries were mostly similar to the ISO 7029 data but tended to deviate in some age groups and sexes. As national hearing threshold trends change, the following ISO 7029 revision suggests the need to integrate hearing threshold data from different countries.

Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards.

This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.

Enhanced Double Metal Cyanide Catalysts for Modulating the Rheological Properties of Poly(propylene carbonate) Polyols by Modifying Carbonate Contents.

Poly(propylene carbonate) (PPC) polyol is an environmentally sustainable material derived from abundant and renewable greenhouse gas, CO2. Optimizing their synthesis and properties is crucial to their application in the production of polyurethane products. In this study, we synthesized PPC polyols with varying carbonate contents using heterogeneous Zn/Co double metal cyanide (DMC) catalysts, which were prepared with poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123) as an effective complexing agent. Analysis of the influence of calcination temperature revealed that the DMC-P123 catalyst calcined at 100 °C exhibited superior catalytic performance owing to reduced crystallinity and enhanced formation of the monoclinic phase. Additionally, by precisely controlling the CO2 pressure, high propylene carbonate contents of up to 32.8 wt % in the polyol structure were achieved. The increased carbonate content enhanced the intermolecular attraction between polyol chains, thereby promoting hydrogen bonding and significantly modulating the rheological properties of the polyol. The novel findings of this study establish a solid foundation for the synthesis of CO2-based polyols with desirable properties, serving as alternatives to conventional petroleum-based polyols.

DNA Damage Triggers the Activation of Immune Response to Viral Pathogens via Salicylic Acid in Plants.

Plants are challenged by various pathogens throughout their lives, such as bacteria, viruses, fungi, and insects; consequently, they have evolved several defense mechanisms. In addition, plants have developed localized and systematic immune responses due to biotic and abiotic stress exposure. Animals are known to activate DNA damage responses (DDRs) and DNA damage sensor immune signals in response to stress, and the process is well studied in animal systems. However, the links between stress perception and immune response through DDRs remain largely unknown in plants. To determine whether DDRs induce plant resistance to pathogens, Arabidopsis plants were treated with bleomycin, a DNA damage-inducing agent, and the replication levels of viral pathogens and growth of bacterial pathogens were determined. We observed that DDR-mediated resistance was specifically activated against viral pathogens, including turnip crinkle virus (TCV). DDR increased the expression level of pathogenesis-related (PR) genes and the total salicylic acid (SA) content and promoted mitogen-activated protein kinase signaling cascades, including the WRKY signaling pathway in Arabidopsis. Transcriptome analysis further revealed that defense- and SA-related genes were upregulated by DDR. The atm-2atr-2 double mutants were susceptible to TCV, indicating that the main DDR signaling pathway sensors play an important role in plant immune responses. In conclusion, DDRs activated basal immune responses to viral pathogens.

Partial Purification and Biochemical Evaluation of Protease Fraction (MA-1) from Mycoleptodonoides aitchisonii and Its Fibrinolytic Effect.

The antioxidative proteolytic fraction, MA-1, was partially purified from Mycoleptodonoides aitchisonii. MA-1 was purified to homogeneity using a two-step procedure, which resulted in an 89-fold increase in specific activity and 42.5% recovery. SDS-PAGE revealed two proteins with a molecular weight of 48 kDa. The zymography results revealed proteolytic activity based on the MA-1 band. MA-1 was found to be stable in the presence of Na+, Ca2+, Fe3+, K+, and Mg2+. MA-1 was also stable in methanol, ethanol, and acetone, and its enzyme activity increased by 15% in SDS. MA-1 was inhibited by ethylenediaminetetra-acetic acid or ethylene glycol tetraacetic acid and exerted the highest specificity for the substrate, MeO-Suc-Arg-Pro-Tyr-pNA, for chymotrypsin. Accordingly, MA-1 belongs to the family of chymotrypsin-like metalloproteins. The optimum temperature was 40 °C and stability was stable in the range of 20 to 35 °C. The optimum pH and stability were pH 5.5 and pH 4-11. MA-1 exhibited stronger fibrinolytic activity than plasmin. MA-1 hydrolyzed the Aα, Bß, and γ chains of fibrinogen within 2 h. MA-1 exhibited an antithrombotic effect in animal models. MA-1 was devoid of hemorrhagic activity at a dose of 80,000 U/kg. Overall, our results show that M. aitchisonii produces an acid-tolerant and antioxidative chymotrypsin-like fibrinolytic enzyme, and M. aitchisonii containing MA-1 could be a beneficial functional material for the prevention of cardiovascular diseases and possible complications.

Efficacy of FRO on Acne Vulgaris Pathogenesis.

Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and Cutibacterium acnes (CA: formerly Propionibacterium acnes) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Rhus verniciflua Stokes and Orostachys japonicus, against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.

Analysis of Wheat Virome in Korea Using Illumina and Oxford Nanopore Sequencing Platforms.

Wheat (Triticum aestivum L.) is one of the most important staple crops in the world, along with maize and rice. More than 50 plant viruses are known to infect wheat worldwide. To date, there are no studies on the identification of viruses infecting wheat in Korea. Therefore, we investigated virome in wheat from three different geographical regions where wheat is mainly cultivated in Korea using Oxford Nanopore Technology (ONT) sequencing and Illumina sequencing. Five viral species, including those known to infect wheat, were identified using high-throughput sequencing strategies. Of these, barley virus G (BVG) and Hordeum vulgare endornavirus (HvEV) were consistently present in all libraries. Sugarcane yellow leaf virus (SCYLV) and wheat leaf yellowing-associated virus (WLYaV) were first identified in Korean wheat samples. The viruses identified by ONT and Illumina sequencing were compared using a heatmap. Though the ONT sequencing approach is less sensitive, the analysis results were similar to those of Illumina sequencing in our study. Both platforms served as reliable and powerful tools for detecting and identifying wheat viruses, achieving a balance between practicality and performance. The findings of this study will provide deeper insights into the wheat virosphere and further help improve disease management strategies.

Rapid Identification of Jasmine Virus H Infecting Ixora coccinea by Nanopore Metatranscriptomics.

The global climate change and international trade have facilitated the movement of plants across borders, increasing the risk of introducing novel plant viruses in new territories. Ixora coccinea exhibited virus-like foliar symptoms, including mosaic and mild mottle. An Oxford Nanopore Technologies-based compact and portable MinION platform was used to identify the causal viral pathogen. The complete genome sequence of jasmine virus H (JaVH; 3867 nt, JaVH-CNU) was determined and found to share 88.4-90.3% nucleotide identity with that of Jasminum sambac JaVH isolate in China. Phylogenetic analysis based on the complete amino acid sequences of RNA-dependent RNA polymerase and coat protein revealed that JaVH-CNU was grouped separately with other JaVH isolates. This is the first report of a natural JaVH infection of >i<I. coccinea. The application of rapid nanopore sequencing for plant virus identification was demonstrated and is expected to provide accurate and rapid diagnosis for virus surveillance.

The effect of noise on the cortical activity patterns of speech processing in adults with single-sided deafness.

The most common complaint in people with single-sided deafness (SSD) is difficulty in understanding speech in a noisy environment. Moreover, the neural mechanism of speech-in-noise (SiN) perception in SSD individuals is still poorly understood. In this study, we measured the cortical activity in SSD participants during a SiN task to compare with a speech-in-quiet (SiQ) task. Dipole source analysis revealed left hemispheric dominance in both left- and right-sided SSD group. Contrary to SiN listening, this hemispheric difference was not found during SiQ listening in either group. In addition, cortical activation in the right-sided SSD individuals was independent of the location of sound whereas activation sites in the left-sided SSD group were altered by the sound location. Examining the neural-behavioral relationship revealed that N1 activation is associated with the duration of deafness and the SiN perception ability of individuals with SSD. Our findings indicate that SiN listening is processed differently in the brains of left and right SSD individuals.