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BackgroundAtypical peak alpha frequency (PAF) has been reported in children with autism spectrum disorder (ASD); however, the relationships between PAF, age, and autistic traits remain unclear. This study was conducted to investigate and compare the resting-state PAF of young children with ASD and their typically developing (TD) peers using magnetoencephalography (MEG).MethodsNineteen children with ASD and 24 TD children, aged 5-7 years, underwent MEG under resting-state conditions. The PAFs in ten brain regions were calculated, and the associations between these findings, age, and autistic traits, measured using the Social Responsiveness Scale (SRS), were examined.ResultsThere were no significant differences in PAF between the children with ASD and the TD children. However, a unique positive association between age and PAF in the cingulate region was observed in the ASD group, suggesting the potential importance of the cingulate regions as a neurophysiological mechanism underlying distinct developmental trajectory of ASD. Furthermore, a higher PAF in the right temporal region was associated with higher SRS scores in TD children, highlighting the potential role of alpha oscillations in social information processing.ConclusionsThis study emphasizes the importance of regional specificity and developmental factors when investigating neurophysiological markers of ASD. The distinct age-related PAF patterns in the cingulate regions of children with ASD and the association between right temporal PAF and autistic traits in TD children provide novel insights into the neurobiological underpinnings of ASD. These findings pave the way for future research on the functional implications of these neurophysiological patterns and their potential as biomarkers of ASD across the lifespan.

Transformer models have revolutionized fields like Natural Language Processing (NLP) by enabling machines to accurately understand and generate human language. However, these models’ inherent complexity and limited interpretability pose barriers to their broader adoption. To address these challenges, we propose a simplified query-only attention mechanism specifically for encoder-based transformer models to reduce complexity and improve interpretability. Unlike conventional attention mechanisms, which rely on query (Q), key (K), and value (V) vectors, our method uses only the Q vector for attention calculation. This approach reduces computational complexity while maintaining the model’s ability to capture essential relationships, enhancing interpretability. We evaluated the proposed query-only attention on an EEG conformer model, a state-of-the-art architecture for EEG signal classification. We demonstrated that it performs comparably to the original QKV attention mechanism, while simplifying the model’s architecture. Our findings suggest that query-only attention offers a promising direction for the development of more efficient and interpretable transformer-based models, with potential applications across various domains beyond NLP.

Abstract Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.

Abstract Aim The receptive language ability of individuals with autism spectrum disorder (ASD) seems to lag behind expressive language ability. Several autism‐related genes may influence this developmental delay. Polymorphism of one such gene, namely, the contactin‐associated protein‐like 2 gene (CNTNAP2), affects receptive language in individuals with language delay. However, the association between CNTNAP2 polymorphism and receptive language in individuals with no language delay remains unclear. Methods We included 59 children with ASD and 57 children with typical development in this study and investigated this association using coarse‐grained exact matching. Results We present the first evidence of an association between CNTNAP2 rs2710102 (A‐allele carrier) and reduced receptive language ability in children with ASD whose language development was not delayed. Similarly, among children with typical development, A‐allele carriers had lower receptive language ability, but the difference was non‐significant. Conclusions It is possible that the effect of rs2710102 on receptive language ability is larger in the presence of autism‐related genes. Consequently, we speculate that the effect of rs2710102 on receptive language ability would be exerted in combination with other genes. These findings provide new insights into the genetic interactions between mutations associated with common language disorders and ASD and identify molecular mechanisms and risk alleles that contribute to receptive vocabulary. These findings also provide practical guidance in terms of providing candidate genetic markers that may provide opportunities for targeted early intervention to stratify risk and improve prognosis for poor receptive language development in children with ASD.

Abstract Aim This study aimed to investigate gamma oscillations related to face processing of children with autism spectrum disorders and typically developed children using magnetoencephalography. Methods We developed stimuli that included naturalistic real‐time eye‐gaze situations between participants and their mothers. Eighteen young children with autism spectrum disorders (62−97 months) and 24 typically developed children (61−79 months) were included. The magnetoencephalography data were analyzed in the bilateral banks of the superior temporal sulcus, fusiform gyrus, and pericalcarine cortex for frequency ranges 30–59 and 61–90 Hz. The gamma oscillation normalized values were calculated to compare the face condition (children gazing at mother's face) and control measurements (baseline) using the following formula: (face − control)/(face + control). Results The results revealed significant differences in gamma oscillation normalized values in the low gamma band (30–59 Hz) in the right banks of the superior temporal sulcus, right fusiform gyrus, and right pericalcarine cortex between children with autism spectrum disorders and typically developed children. Furthermore, there were significant differences in gamma oscillation normalized values in the high gamma band (61–90 Hz) in the right banks of the superior temporal sulcus, bilateral fusiform gyrus, and bilateral pericalcarine cortex between the groups. Conclusion This report is the first magnetoencephalography study revealing atypical face processing in young children with autism spectrum disorders using relevant stimuli between participants and their mothers. Our naturalistic paradigm provides a useful assessment of social communication traits and a valuable insight into the underlying neural mechanisms in children with autism spectrum disorders.

Abstract Aim Although atypical sensory motor processing has been investigated in children with autism spectrum disorder (ASD), whether or not atypical sensory motor processing is related to altered language function in children with ASD remains unclear. Methods This study examined the relationship between sensory motor processing and language conceptual inference ability in 3–10‐year‐old children with (n = 61) and without (n = 114) ASD. Language performance was assessed using the language conceptual inference task of the Kaufman Assessment Battery for Children (K‐ABC). Sensory processing was assessed using the Caregiver Sensory Profile. Results In children with ASD, altered processing of the fine motor/perceptual factor scored by sensory profile was found to be significantly related to language conceptual inference ability in the K‐ABC, representing the integrated abilities of language comprehension and language expression, which reflect language semantic concept formation. Conclusions For children with ASD, the results suggest a relationship between difficulties of integrating sensory information perceived from the body adjusting fine movement and deficiencies of language semantic conceptual formation.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an early onset and a strong genetic origin. Unaffected relatives may present similar but subthreshold characteristics of ASD. This broader autism phenotype is especially prevalent in the parents of individuals with ASD, suggesting that it has heritable factors. Although previous studies have demonstrated brain morphometry differences in ASD, they are poorly understood in parents of individuals with ASD. Here, we estimated grey matter volume in 45 mothers of children with ASD (mASD) and 46 age-, sex-, and handedness-matched controls using whole-brain voxel-based morphometry analysis. The mASD group had smaller grey matter volume in the right middle temporal gyrus, temporoparietal junction, cerebellum, and parahippocampal gyrus compared with the control group. Furthermore, we analysed the correlations of these brain volumes with ASD behavioural characteristics using autism spectrum quotient (AQ) and systemizing quotient (SQ) scores, which measure general autistic traits and the drive to systemize. Smaller volumes in the middle temporal gyrus and temporoparietal junction correlated with higher SQ scores, and smaller volumes in the cerebellum and parahippocampal gyrus correlated with higher AQ scores. Our findings suggest that atypical grey matter volumes in mASD may represent one of the neurostructural endophenotypes of ASD.

Measuring whole brain networks is a promising approach to extract features of autism spectrum disorder (ASD), a brain disorder of widespread regions. Objectives of this study were to evaluate properties of resting-state functional brain networks in children with and without ASD and to evaluate their relation with social impairment severity. Magnetoencephalographic (MEG) data were recorded for 21 children with ASD (7 girls, 60–89 months old) and for 25 typically developing (TD) control children (10 girls, 60–91 months old) in a resting state while gazing at a fixation cross. After signal sources were localized onto the Desikan–Killiany brain atlas, statistical relations between localized activities were found and evaluated in terms of the phase lag index. After brain networks were constructed and after matching with intelligence using a coarsened exact matching algorithm, ASD and TD graph theoretical measures were compared. We measured autism symptoms severity using the Social Responsiveness Scale and investigated its relation with altered small-worldness using linear regression models. Children with ASD were found to have significantly lower small-worldness in the beta band (p = 0.007) than TD children had. Lower small-worldness in the beta band of children with ASD was associated with higher Social Responsiveness Scale total t-scores (p = 0.047). Significant relations were also inferred for the Social Awareness (p = 0.008) and Social Cognition (p = 0.015) sub-scales. Results obtained using graph theory demonstrate a difference between children with and without ASD in MEG-derived resting-state functional brain networks, and the relation of that difference with social impairment. Combining graph theory and MEG might be a promising approach to establish a biological marker for ASD.

Autism spectrum disorder (ASD) often involves dysfunction in general motor control and motor coordination, in addition to core symptoms. However, the neural mechanisms underlying motor dysfunction in ASD are poorly understood. To elucidate this issue, we focused on brain oscillations and their coupling in the primary motor cortex (M1). We recorded magnetoencephalography in 18 children with ASD, aged 5 to 7 years, and 19 age- and IQ-matched typically-developing children while they pressed a button during a video-game-like motor task. The motor-related gamma (70 to 90 Hz) and pre-movement beta oscillations (15 to 25 Hz) were analyzed in the primary motor cortex using an inverse method. To determine the coupling between beta and gamma oscillations, we applied phase-amplitude coupling to calculate the statistical dependence between the amplitude of fast oscillations and the phase of slow oscillations. We observed a motor-related gamma increase and a pre-movement beta decrease in both groups. The ASD group exhibited a reduced motor-related gamma increase and enhanced pre-movement beta decrease in the ipsilateral primary motor cortex. We found phase-amplitude coupling, in which high-gamma activity was modulated by the beta rhythm in the primary motor cortex. Phase-amplitude coupling in the ipsilateral primary motor cortex was reduced in the ASD group compared with the control group. Using oscillatory changes and their couplings, linear discriminant analysis classified the ASD and control groups with high accuracy (area under the receiver operating characteristic curve: 97.1%). The current findings revealed alterations in oscillations and oscillatory coupling, reflecting the dysregulation of motor gating mechanisms in ASD. These results may be helpful for elucidating the neural mechanisms underlying motor dysfunction in ASD, suggesting the possibility of developing a biomarker for ASD diagnosis.

Autism spectrum disorders (ASD) are characterized by impaired social cognition and communication. In addition to social impairment, individuals with ASD often have intellectual disability. Intelligence is known to influence the phenotypic presentation of ASD. Nevertheless, the relation between intelligence and social reciprocity in people with ASD remains unclear, especially in childhood. To elucidate this relation, we analyzed 56 typically developing children (35 male, 21 female, aged 60-91 months) and 46 children with ASD (35 male, 11 female, aged 60-98 months) from university and affiliated hospitals. Their cognitive function was evaluated using the Kaufman Assessment Battery for Children. Their social cognition was assessed using the Social Responsiveness Scale. We used linear regression models to ascertain whether the associations between intelligence and social cognition of typically developing children and children with ASD are significantly different. Among the children with ASD, scores on the Kaufman Assessment Battery for Children correlated significantly with social cognition, indicating that higher intelligence is associated with better social cognition. For typically developing children, however, no significant correlation was found. One explanation might be that children with ASD fully use general intelligence for successful learning in social cognition, although extensive use of intelligence might not be necessary for TD children. Alternatively, autistic impairment in social cognition can be compensated by intelligence despite a persistent deficit in social cognition. In either case, when using the SRS as a quantitative phenotype measure for ASD, the influence of intelligence must be considered.

Abstract Background A growing body of anecdotal evidence indicates that the use of robots may provide unique opportunities for assisting children with autism spectrum disorders (ASD). However, previous studies investigating the effects of interventions using robots on joint attention (JA) in children with ASD have shown insufficient results. The robots used in these studies could not turn their eyes, which was a limitation preventing the robot from resembling a human agent. Methods We compared the behavior of children with ASD with that of children with typical development (TD) during a JA elicitation task while the children interacted with either a human or a robotic agent. We used the robot “CommU,” which has clear eyes and can turn its eyes, for the robotic intervention. The age range of the participants was limited to 5–6 years. Results Sixty-eight participants participated in this study, including 30 (10 females and 20 males) children with ASD and 38 (13 females and 25 males) children with TD. The participants were randomly assigned to one of the following two groups: the robotic intervention group or the control group. JA in the children with ASD was better during the robotic intervention than during the human agent intervention. These children exhibited improved performance in the JA task with human after interacting with the robot CommU. JA was differentially facilitated by the human and robotic agents between the ASD and TD children. Conclusions The findings of this study significantly contribute to the literature on the impact of robots on JA and provide information regarding the suitability of specific robot types for therapeutic use.

Objectives: Insomnia, characterized by difficulty initiating or maintaining sleep, affects a significant portion of the global population. Bedtime procrastination, which is a voluntary delay in going to bed, is a major contributing factor to the prevalence of sleep deprivation in modern societies. Hwanglyeonhaedok-tang (HJD decoction) has shown promise in improving the symptoms of insomnia. This study aimed to evaluate the efficacy of HJD decoction in patients with insomnia and bedtime procrastination.Methods: This study employs a parallel-group design, comparing HJD decoction to usual care in a 1:1 ratio. Sixty participants with insomnia and bedtime procrastination will be enrolled. The experimental group will receive HJD decoction for 4 weeks, while both groups will undergo a brief behavioral treatment for insomnia. The primary outcome will be the change in the Insomnia Severity Index score (ISI) from baseline to 4 weeks. Secondary outcomes include sleep diary metrics, the Pittsburgh Sleep Quality Index (PSQI), and Bedtime Procrastination Scale (BPS). The exploratory outcomes include perceived stress, anxiety, smartphone use, and heart rate variability.Conclusion: This trial examines the role of herbal medicine in treating a specific type of insomnia that is increasingly common in modern society. The combination of HJD decoction with behavioral intervention offers a comprehensive approach to treating insomnia complicated by bedtime procrastination. The results will provide valuable insights into integrative treatment strategies for sleep disorders in the digital age.

Background: Invasive laser acupuncture (ILA) involves simultaneous application of focused laser irradiation and acupuncture. This study aims to explore the effects of ILA on knee osteoarthritis (KOA) through a pilot clinical trial. Methods: This prospective, patient-blinded, single-center, and parallel-arm pilot randomized controlled trial will enroll 45 patients with KOA randomized to the control, 830, and 650 groups. All patients will receive education on exercise and self-care. Their ILA treatment will correspond to their group (control group, sham; 830 group, 830 nm; 650 group, 650-nm wavelength laser) for 10 minutes once daily, twice weekly for 6 weeks at EX-LE4, ST35, ST34, SP10, SP9, GB34, and EXLE2 acupoints. Results: The primary endpoint will be changes in the visual analog scale (VAS) score of pain at rest and during activity 1 week after interventions (week 7). The secondary outcomes will be the responder rate; VAS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain subscale, WOMAC function subscale, European quality of life five-dimension five-level scale, and patient global assessment scores; and rescue medication doses. Safety outcome measures will include blood chemistry parameters, occurrence of adverse events, pulse rate, and blood pressure. The efficacy outcomes will be measured at baseline, visit after six treatments, 1 week after the last treatment, and 6 weeks after the last treatment. Conclusion: The findings will provide preliminary data on the effects of ILA on KOA.

Electroencephalograms of individuals with autism spectrum disorders (ASD) show higher rates of interictal epileptiform discharges (IEDs), which are known to have an inverse association with cognitive function in typically developed (TD) children. Nevertheless, that phenomenon has not been investigated adequately in children with ASD. From university and affiliated hospitals, 163 TD children (84 male, 79 female, aged 32–89 months) and 107 children (85 male, 22 female, aged 36–98 months) with ASD without clinical seizure were recruited. We assessed their cognitive function using the Kaufman Assessment Battery for Children (K-ABC) and recorded 10 min of MEG. Original waveforms were visually inspected. Then a linear regression model was applied to evaluate the association between the IED frequency and level of their cognitive function. Significantly higher rates of IEDs were found in the ASD group than in the TD group. In the TD group, we found significant negative correlation between mental processing scale scores (MPS) and the IED frequency. However, for the ASD group, we found significant positive correlation between MPS scores and the IED frequency. In terms of the achievement scale, correlation was not significant in either group. Although we found a correlative rather than a causal effect, typically developed children with higher IED frequency might better be followed up carefully. Furthermore, for children with ASD without clinical seizure, clinicians might consider IEDs as less harmful than those observed in TD children.

The COVID-19 pandemic forced the rapid development of methods to measure humoral and cellular immunity against SARS-CoV-2. The lack of a global standardized protocol and the high variability of intra- and inter-assay precision of the T-cell response made it difficult to compare T-cell assay results with those of other laboratories. The interferon-gamma enzyme-linked immunosorbent spot (IFN-γ ELISpot) assay for immunogenicity evaluation was validated using naturally infected donor peripheral blood mononuclear cells, a commercially available IFN-γ ELISpot kit, and a SARS-CoV-2 specific peptide pool. Depending on anti-CD3 and peptide pool stimulation, the mean coefficients of variation (CVs) of the intra-assay precision were 19.0% and 13.4%, respectively. The mean CVs of the inter-assay precision were 26.1% and 25.4%, and the mean CVs for reproducibility were 6.7% and 15.9%, respectively. Linearity with an R-squared value between 0.98 and 0.99 was established, and the mean CVs between the lots were 17.6% and 6.6%, depending on the anti-CD3 and peptide pool stimulation, respectively. The limit of detection was 11 spot-forming counts per well. Taken together, we demonstrated that the IFN-γ ELISpot assay is feasible for evaluating SARS-CoV-2-specific cell-mediated immune function through validation based on standard operating procedures.

Phase-amplitude coupling (PAC) plays an important role in neural communication and computation. Interestingly, recent studies have indicated the presence of ubiquitous PAC phenomenon even during the resting state. Despite the importance of PAC phenomenon, estimation of significant physiological PAC is challenging because of the lack of appropriate surrogate measures to control false positives caused by non-physiological PAC. Therefore, in the present study, we evaluated PAC phenomenon during resting-state magnetoencephalography (MEG) signal and considered various surrogate measures and computational approaches widely used in the literature in addition to proposing new ones. We evaluated PAC phenomenon over the entire length of the MEG signal and for multiple shorter time segments. The results indicate that the extent of PAC phenomenon mainly depends on the surrogate measures and PAC computational methods used, as well as the evaluation approach. After a careful and critical evaluation, we found that resting-state MEG signals failed to exhibit ubiquitous PAC phenomenon, contrary to what has been suggested previously.

Fault classification in power transmission lines is important in distance relaying for identifying the accurate phases implicated in the fault occurrence. Generally, the accuracy of fault classification algorithms is evaluated by simulation data, which shows quite different characteristics from real fault data. Also, most of the previous works on fault classification used a single-stage method such as a rule-based algorithm or machine learning-based algorithm. Because of the diverse characteristics of real fault data, the performance of the single-stage method is limited. To address these issues, this paper proposes a novel two-stage algorithm that combines the strengths of rule-based and machine-learning algorithms to improve the accuracy of real fault data. A case study using real fault data shows that the proposed two-stage algorithm outperforms other conventional single-stage algorithms.

In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive technique for monitoring brain metabolites. However, it is challenged by a low signal-to-noise ratio (SNR), often necessitating extended scan times to compensate. One of the conventional techniques for noise reduction is signal averaging, which is inherently time-consuming and can lead to participant discomfort, thus posing limitations in clinical settings. This study aimed to develop a hybrid denoising strategy that integrates low-rank approximation and denoising diffusion probabilistic model (DDPM) to enhance MRS data quality and shorten scan times. Using publicly available 1H MRS datasets from 15 subjects, we applied the Casorati SVD and DDPM to obtain baseline and functional data during a pain stimulation task. This method significantly improved SNR, resulting in outcomes comparable to or better than averaging over 32 signals. It also provided the most consistent metabolite measurements and adequately tracked temporal changes in glutamate levels, correlating with pain intensity ratings after heating. These findings demonstrate that our approach enhances MRS data quality, offering a more efficient alternative to conventional methods and expanding the potential for the real-time monitoring of neurochemical changes. This contribution has the potential to advance MRS techniques by integrating advanced denoising methods to increase the acquisition speed and enhance the precision of brain metabolite analyses.

This study investigates the impact of exogenous calcium and gamma-aminobutyric acid (GABA) supplementation on rice growth and stress tolerance under white-backed planthopper (WBPH) infestation. We evaluated several phenotypic traits, including shoot/root length, leaf width, tiller number, panicle length, and relative water content, alongside physiological markers such as oxidative stress indicators, antioxidant enzymes activities, hormonal levels, and amino acids biosynthesis. Our results indicate that WBPH stress significantly reduces growth parameters but calcium and GABA supplementation markedly enhance shoot length (by 26% and 36%) and root length (by 38% and 64%), respectively, compared to WBPH-infested plants. Both supplementations also reduced oxidative stress, as evidenced by decreased H2O2 and O2•− levels and a lower electrolyte leakage. Notably, calcium and GABA treatments increased antioxidant enzyme activities, with GABA boosting catalase (CAT) activity by 800%, peroxidase (POD) by 144%, and superoxide dismutase (SOD) by 62% under WBPH stress. Additionally, calcium and GABA enhanced the accumulation of stress hormones (abscisic acid ABA) and salicylic acid (SA) and promoted stomatal closure, contributing to improved water conservation. This study reveals that calcium regulates the GABA shunt pathway, significantly increasing GABA and succinate levels in both root and shoot. Furthermore, calcium and GABA supplementation enhance the biosynthesis of key amino acids and improve ion homeostasis, particularly elevating calcium (Ca), iron (Fe), and magnesium (Mg) levels under WBPH stress. Overall, this study highlights the potential of exogenous calcium and GABA as effective strategies for enhancing rice plant tolerance to WBPH infestation by modulating various physiological and biochemical mechanisms. Further research is warranted to fully elucidate the underlying mechanisms of action.

Mycobacterium avium complex (MAC) infection is a growing public health concern worldwide, particularly affecting the elderly and immunocompromised population. The treatment of MAC lung disease relies on a combination of antibiotics in a three-drug regimen that includes macrolides, rifamycins, and ethambutol. Therefore, the investigation of antimicrobial susceptibility is crucial for successful treatment. This study aimed to assess the antibiotic susceptibility of the most prevalent MAC species causing MAC lung disease, Mycobacterium intracellulare, in the Southwestern Gyeongsang province of South Korea using a resazurin-based microtiter assay. A total of 97 strains of M. intracellulare were isolated and tested for antimicrobial susceptibility. The results demonstrated high susceptibility rates for two aminoglycosides (amikacin and streptomycin, 94.9% and 99%), rifampicin (90.9%), clarithromycin (98%), linezolid (100%), and moxifloxacin (94.9%) against M. intracellulare. However, notably high resistance rates were observed for ethambutol (97%) and clofazimine (98%) against M. intracellulare. In conclusion, our findings indicate relatively high susceptibility rates for these six antibiotics and significantly elevated resistance rates for clofazimine and ethambutol compared to other regions in South Korea and foreign countries. The investigated MIC data can offer valuable insights for developing an effective treatment regimen for MAC lung infection in this area.

Abstract The COVID‐19 pandemic disrupted prostate‐specific antigen (PSA) screening and prostate biopsy procedures. We sought to determine whether delayed screening and diagnostic workup of prostate cancer (PCa) was associated with increased subsequent rates of incident PCa and advanced PCa and whether the rates differed by race. We analyzed data from the Veterans Health Administration to assess the changes in the rates of PSA screening, prostate biopsy procedure, incident PCa, PCa with high‐grade Gleason score, and incident metastatic prostate cancer (mPCa) before and after January 2020. While the late pandemic mPCa rate among White Veterans was comparable to the pre‐pandemic rate (5.4 pre‐pandemic vs 5.2 late‐pandemic, p = 0.67), we observed a significant increase in incident mPCa cases among Black Veterans in the late pandemic period (8.1 pre‐pandemic vs 11.3 late‐pandemic, p

In situ crosslinkable hydrogels have been widely used as therapeutic implants and vehicles for a broad range of biomedical applications including tissue regenerative medicine because of their biocompatibility and easiness of encapsulation of cells or signaling molecules during hydrogel formation. Recently, these hydrogel materials have been widely utilized as an artificial extracellular matrix (aECM) because of its structural similarity with the native extracellular matrix (ECM) of the human body and its multi-tunable properties. Various synthetic, natural, and semisynthetic hydrogels have been developed as engineered cellular microenvironments by using various crosslinking strategies. In this review, we discuss how in situ forming hydrogels are being created with tunable physical, chemical, and biological properties. In particular, we focus on emerging techniques to apply advanced hydrogel materials for engineered cellular microenvironments.

Abstract Melatonin is a bioactive molecule with an important role in plants responding to various abiotic and biotic stresses. This study aims to determine the role of melatonin in rice under salt stress. This study used a factorial completely randomized design. The first factor was local rice varieties (IR64 and Silaun), and the second factor was plant treatments (control, 1 µM melatonin, 150 mM NaCl, 150 mM NaCl + 1µM melatonin). This study shows that exogenous melatonin can increase plant growth, such as plant height, root length, stem length, leaf length, leaf area, and plant biomass under salt stress compared to treatment without melatonin. Exogenous melatonin can increase the total chlorophyll content, relative water content, and proline content, reduce the total sodium content, and increase potassium absorption under conditions of salinity stress. Melatonin is also able to scavenge ROS in plants, resulted the decrease in ROS and MDA content. In terms of gene expression, OsAPX1 and cytosolic APX exhibited the highest expression in IR64 under combined salt and melatonin treatment, while GPOD, Mn-SOD, and Cu/Zn-SOD were upregulated under various conditions in both varieties. Additionally, OsLEA showed high expression in both varieties under control conditions, and CAT was significantly upregulated under salt stress. Our findings indicate that exogenous melatonin has the potential to enhance various factors under salt stress and helping in the recovery of rice plants from sodium (Na+) damage.

Heat stress and drought are combination of stresses that have the potential to occur simultaneously in extreme temperature changes. Rice is the main food crop in Indonesia and includes plants that are sensitive to stress. Indonesian local rice is believed to have high adaptability to Indonesian's geographical conditions, however there is lack of updated data to explain this information. This study attempts to determine the level of adaptability or resistance of Indonesian local rice to a combination of heat stress and drought. The results showed that the 24 Indonesian local rice accessions were divided into 3 resistance classes. The high resistance class is Sintha, the resistance classes are Gajah Mungkur, Kalimutu, Kapuas, Sukamandi, Seratus Malam, Cabacu, Bengawan Solo and Cisokan, as well as the medium resistance classes Jatiluhur, Batang Ombilin, Mahakam, Nona Bokra, Pucuk, Bengawan, Rojolele, IR64, Barumun, Cisadane, Memberamo, Cibodas, Gilirang, Fatmawati and Ciherang.

Abstract Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutate histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here, we find that H3.3K9 is essential for controlling specific distal intergenic regions and for proper H3K27me3 deposition at promoters. The H3.3K9A mutation resulted in decreased H3K9me3 at regions encompassing endogenous retroviruses and induced a gain of H3K27ac and nascent transcription. These changes in the chromatin environment unleash cryptic enhancers, resulting in the activation of distinctive transcriptional programs and culminating in protein expression normally restricted to specialized immune cell types. The H3.3K27A mutant disrupts the deposition and spreading of the repressive H3K27me3 mark, particularly impacting bivalent genes with higher basal levels of H3.3 at promoters. Therefore, H3.3K9 and K27 crucially orchestrate repressive chromatin states at cis-regulatory elements and bivalent promoters, respectively, and instruct proper transcription in mESCs.

Abstract Background Photoperiod sensitivity is among the most important agronomic traits of rice, as it determines local and seasonal adaptability and plays pivotal roles in determining yield and other key agronomic characteristics. By controlling the photoperiod, early-maturing rice can be cultivated to shorten the breeding cycle, thereby reducing the risk of yield losses due to unpredictable climate change. Furthermore, early-maturing and high-yielding rice needs to be developed to ensure food security for a rapidly growing population. Early-maturing and high-yielding rice should be developed to fulfill these requirements. OsCKq1 encodes the casein kinase1 protein in rice. OsCKq1 is a gene that is activated by photophosphorylation when Ghd7, which suppresses flowering under long-day conditions, is activated. Results This study investigates how OsCKq1 affects heading in rice. OsCKq1-GE rice was analyzed the function of OsCKq1 was investigated by comparing the expression levels of genes related to flowering regulation. The heading date of OsCKq1-GE lines was earlier (by about 3 to 5 days) than that of Ilmi (a rice cultivar, Oryza sativa spp. japonica), and the grain length, grain width, 1,000-grain weight, and yield increased compared to Ilmi. Furthermore, the culm and panicle lengths of OsCKq1-GE lines were either equal to or longer than those of Ilmi. Conclusions Our research demonstrates that OsCKq1 plays a pivotal role in regulating rice yield and photoperiod sensitivity. Specifically, under long-day conditions, OsCKq1-GE rice exhibited reduced OsCKq1 mRNA levels alongside increased mRNA levels of Hd3a, Ehd1, and RFT1, genes known for promoting flowering, leading to earlier heading compared to Ilmi. Moreover, we observed an increase in seed size. These findings underscore OsCKq1 as a promising target for developing early-maturing and high-yielding rice cultivars, highlighting the potential of CRISPR/Cas9 technology in enhancing crop traits.

Introduction: The stem cell microenvironment has been evidenced to robustly affect its biological functions and clinical grade. Natural or synthetic growth factors, especially, are essential for modulating stem cell proliferation, metabolism, and differentiation via the interaction with specific extracellular receptors. Fibroblast growth factor-2 (FGF-2) possesses pleiotropic functions in various tissues and organs. It interacts with the FGF receptor (FGFR) and activates FGFR signaling pathways, which involve numerous biological functions, such as angiogenesis, wound healing, cell proliferation, and differentiation. Objectives: Here, we aim to explore the molecular functions, mode of action, and therapeutic activity of yet undetermined function, FGF-2-derived peptide, FP2 (44-ERGVVSIKGV-53) in promoting the proliferation, differentiation, and therapeutic application of human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) in comparison to other test peptides, canofin1 (FP1), hexafin2 (FP3), and canofin3 (FP4) with known functions. Methods: The immobilization of test peptides that are fused with mussel adhesive proteins (MAP) on the culture plate was carried out via EDC/NHS chemistry. Cell Proliferation assay, colony-forming unit, western blotting analysis, gene expression analysis, RNA-Seq. analysis, osteogenic, and chondrogenic differentiation capacity were applied to test the activity of the test peptides. We additionally utilized three-dimensional (3D) structural analysis and artificial intelligence (AI)-based AlphaFold2 and CABS-dock programs for receptor interaction prediction of the peptide receptor. We also verified the in vivo therapeutic capacity of FP2-cultured hWJ-MSCs using an osteoarthritis mice model. Results: Culture of hWJ-MSC onto an FP2-immobilized culture plate showed a significant increase in cell proliferation (n = 3; *p

Muscular imbalance increases the risk of non-contact injuries among youth athletes. This study aimed to examine the isokinetic hamstring-to-quadriceps strength (H/Q) ratios between the dominant and non-dominant legs in youth taekwondo (TKD) players. Sixty-three youth TKD players voluntarily participated in this study. The isokinetic muscle strength test was performed at three different angular velocities (60°·s−1, 120°·s−1 and 240°·s−1) with concentric (Con) and eccentric (Ecc) contraction modes. The conventional (HCon/QCon) and functional (HEcc/QCon) H/Q strength ratios were determined. Hamstring muscle strength was significantly greater in the dominant leg than in the non-dominant leg at 60°·s−1 (Con contraction) and at 120°·s−1 and 240°·s−1 (Ecc contraction). Conventional and functional H/Q strength ratios were higher in the dominant leg than in the non-dominant leg at 240°·s−1, and the strength ratios increased with angular velocity. The asymmetry of conventional and functional H/Q strength ratios between the dominant and non-dominant legs may affect the risk of non-contact injuries among youth TKD players; thus, coaches should include specialized training programs to balance the H/Q strength ratios between legs. In particular, unilateral eccentric hamstring exercises for the nondominant leg are important for preventing noncontact injuries.

Abstract Homomorphic encryption performs computations on encrypted data without decrypting, thereby eliminating security issues during the data communication between clouds and edges. As a result, there is a growing need for homomorphic encryption hardware (HE-HW) for the edges, where low power consumption and a compact form factor are desired. Here, a Pt/Ta2O5/Mo metallic cluster-type memristors (Mo-MCM) characterized by the Mo as a mobile species, and its utilization for the HE-HW via a 1-trasistor-1-memristor (1T1M) array as a prototype HE-HW is proposed. The Mo-MCM exhibits inherent stochastic set-switching behavior, which can be utilized for generating the random numbers required for encryption key generation. Furthermore, the device can accurately store analog conductance states after set-switching, which can be used as an analog non-volatile memristor. By simultaneously leveraging these two characteristics, encryption key generation, data encryption, and decryption are possible within a single device through an in-memory computing manner.

Microbes are critical contributors in main areas of biotechnology, including green, red, and white biotechnology. This is why the importance of the preservation of microbial resources cannot be emphasized enough. Culture collections are repositories not only for the preservation and maintenance of a large variety of microbial resources and the associated data but also for their distribution in a quality-controlled manner. The mission of culture collections facilitates and supports utilization of microbial resources for research, education, and industrial purposes. Led by the World Federation for Culture Collections, an international organization committed to fostering the activities of culture collections of microorganisms and cell lines, more than 850 culture collections from 80 countries and regions work together to ensure the perpetuation of microbial resources. In addition, domestic networks, such as Japan Society for Culture Collections and United States Culture Collection Network along with regional networks for Europe, Latin America, and Asia thrive to ensure the long-term viability of microbial resources. The Republic of Korea recently took the first step in networking through the coordination of six ministries which house nine national microbial culture collections. With an explosion in microbiome research and a dramatic increase in the number of microbiome samples, the considerable challenge of culture collections will therefore be implementing the biobanking infrastructure of microbiome samples. Creating a domestic network of national culture collections is a key factor in efficiently and comprehensively managing nation-led microbiome research projects, particularly resulting microbiome samples. In this context, this review aims to provide an overview of microbial culture collection network and their future role to address the challenge in the microbiome era.

Background: Acute lateral ankle sprains (ALAS) are associated with long-term impairments and instability tied to altered neural excitability. Arthrogenic muscle inhibition (AMI) has been observed in this population; however, relationships with injury-related impairments are unclear, potentially due to the resting, prone position in which AMI is typically measured. Assessing AMI during bipedal stance may provide a better understanding of this relationship. Methods: AMI was assessed in 38 young adults (19 ALAS within 72 h of injury: 10 males, 21.4 ± 2.7 years; 19 healthy controls: 10 males, 21.9 ± 2.2 years; mean ± SD) using the Hoffmann reflex (H-reflex) during bipedal stance. Electrical stimulation was administered to identify the maximal H-reflex (Hmax) and maximal motor response (Mmax) from the soleus, fibularis longus, and tibialis anterior muscles. The primary outcome measure was the Hmax/Mmax ratio. Secondary outcomes included acute symptoms (pain and swelling), postural control during bipedal stance, and self-reported function. Results: No significant group-by-limb interactions were observed for any muscle. However, a significant group main effect was observed in the soleus muscle (F(1,35) = 6.82, p = 0.013), indicating significantly lower Hmax/Mmax ratios following ALAS (0.38 ± 0.20) compared to healthy controls (0.53 ± 0.16). Furthermore, lower Hmax/Mmax ratios in the soleus significantly correlated with acute symptoms and self-reported function but not with postural control. Conclusion: This study supports previous evidence of AMI in patients with ALAS, providing insight into neurophysiologic impacts of musculoskeletal injury. Our results suggest that assessing AMI in a standing position following acute injury may provide valuable insight into how AMI develops and guide potential therapeutic options to curb and offset the formation of joint instability.

Introduction: In this study, we aimed to comparatively analyse the indicators of availability to orphan drugs in South Korea, the United States of America, Europe Union, and Japan.Methods: For 169 drugs designated as orphan drugs in South Korea between 2012 and 2021, information on the drugs designated as orphan drugs from each jurisdiction was extracted by country. Then, the availability indicators (approval time, drug lag time, and designation gap) were analysed for the drugs approved in each jurisdiction.Results: The approval rate of drugs designated as orphan drugs were 11.22% and 6.31% in the USA and EU, respectively, which was lower than that of orphan drugs in South Korea and Japan. The highest number of approved drugs was in the USA (87 drugs), EU 27 drugs, Japan 22 drugs and Korea 21 drugs. Furthermore, the approval time significantly differed between South Korea and the other countries. South Korea had a significantly different drug lag time and designation gap compared with the USA and EU.Conclusion: Our findings show that to fundamentally improve the access to treatments for rare disease, a policy of regulatory science that can comprehensively support the early stages of research and development and commercialisation is needed.

AbstractThe urgent demand for effective countermeasures against metallo-β-lactamases (MBLs) necessitates development of novel metallo-β-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.

Abstract In this study, the complete plastome sequence of Nigella sativa (black seed), was analyzed for the first time. The plastome spans approximately 154,120 bp, comprising four sections: the Large Single-Copy (LSC) (85,538 bp), the Small Single-Copy (SSC) (17,984 bp), and two Inverted Repeat (IR) regions (25,299 bp). A comparative study of N. sativa’s plastome with ten other species from various genera in the Ranunculaceae family reveals substantial structural variations. The contraction of the inverted repeat region in N. sativa influences the boundaries of single-copy regions, resulting in a shorter plastome size than other species. When comparing the plastome of N. sativa with those of its related species, significant divergence is observed, particularly except for N. damascena. Among these, the plastome of A. glaucifolium displays the highest average pairwise sequence divergence (0.2851) with N. sativa, followed by A. raddeana (0.2290) and A. coerulea (0.1222). Furthermore, the study identified 12 distinct hotspot regions characterized by elevated Pi values (> 0.1). These regions include trnH-GUG-psbA, matK-trnQ-UUG, psbK-trnR-UCU, atpF-atpI, rpoB-psbD, ycf3-ndhJ, ndhC-cemA, petA-psaJ, trnN-GUU-ndhF, trnV-GAC-rps12, ycf2-trnI-CAU, and ndhA-ycf1. Approximately, 24 tandem and 48 palindromic and forward repeats were detected in N. sativa plastome. The analysis revealed 32 microsatellites with the majority being mononucleotide repeats. In the N. sativa plastome, phenylalanine had the highest number of codons (1982 codons), while alanine was the least common amino acid with 260 codons. A phylogenetic tree, constructed using protein-coding genes, revealed a distinct monophyletic clade comprising N. sativa and N. damascene, closely aligned with the Cimicifugeae tribe and exhibiting robust support. This plastome provides valuable genetic information for precise species identification, phylogenetic resolution, and evolutionary studies of N. sativa.

Abstract Introduction Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. Method A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. Results In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12–4.44) in the high-risk, 4.63 (95% CI 2.34–10.25) in the intermediate-risk and 3.60 (95% CI 3.07–4.24) in the low-risk patients. Conclusion HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

Titanium carbides reinforced steel matrix (TiC-steel) composites exhibit a range of excellent properties, including increased strength-to-weight ratio, high-temperature strength, and outstanding wear resistance. Prior research has demonstrated that the mechanical properties of TiC-steel composites are significantly affected by particle coarsening and the associated core-rim structure. Nevertheless, the fundamental mechanisms of thermochemical reactions that govern the formation of the final microstructure in these composites, including the core-rim structure, remain incompletely explored. This study elucidates the microstructure evolution mechanism of high-volume TiC-steel composites, particularly particle coarsening, through thermodynamic calculations and chemical analysis. The investigation unveils the coarsening process, shedding light on the formation of more stable phases and associated compositional changes, including the incorporation of substitutional elements and carbon depletion (resulting in low stoichiometry, x

Objective: To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter (PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish. Methods: HaCaT cells and zebrafish were used to evaluate the protective effects of the ethyl acetate fraction of Sargassum pallidum extract against PM-induced oxidative stress and inflammation. The production of nitric oxide (NO), intracellular ROS, prostaglandin E2 (PGE2), and pro-inflammatory cytokines, and the expression levels of COX-2, iNOS, and NF-κB were evaluated in PM-induced HaCaT cells. Furthermore, the levels of ROS, NO, and lipid peroxidation were assessed in the PM-exposed zebrafish model. Results: The ethyl acetate fraction of Sargassum pallidum extract significantly decreased the production of NO, intracellular ROS, and PGE2 in PM-induced HaCaT cells. In addition, the fraction markedly suppressed the levels of pro-inflammatory cytokines and inhibited the expression levels of COX-2, iNOS, and NF-κB. Furthermore, it displayed remarkable protective effects against PM-induced inflammatory response and oxidative stress, represented by the reduction of NO, ROS, and lipid peroxidation in zebrafish. Conclusions: The ethyl acetate fraction of Sargassum pallidum extract exhibits a protective effect against PM-induced oxidative stress and inflammation both in vitro and in vivo and has the potential as a candidate for the development of pharmaceutical and cosmeceutical products.

Abstract We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Abstract Background Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer’s disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening. Methods We established AD hPSC lines from normal hPSCs by introducing genes that harbor familial AD mutations, and the COs were generated using these hPSC lines. The pathological features of AD, including extensive amyloid-β (Aβ) accumulation, tauopathy, and neurodegeneration, were analyzed using enzyme-linked immunosorbent assay, Amylo-Glo staining, thioflavin-S staining, immunohistochemistry, Bielschowsky’s staining, and western blot analysis. Results The AD COs exhibited extensive Aβ accumulation. The levels of paired helical filament tau and neurofibrillary tangle-like silver deposits were highly increased in the AD COs. The number of cells immunoreactive for cleaved caspase-3 was significantly increased in the AD COs. In addition, treatment of AD COs with BACE1 inhibitor IV, a β-secretase inhibitor, and compound E, a γ-secretase inhibitor, significantly attenuated the AD pathological features. Conclusion Our model effectively recapitulates AD pathology. Hence, it is a valuable platform for understanding the mechanisms underlying AD pathogenesis and can be used to test the efficacy of anti-AD drugs.

The Quercus genus (oaks) comprises valuable plant resources that are used in many fields, including cosmetics, foods, and pharmaceuticals. Nonetheless, overall chemical profiling and anti-glycation component identification have not been thoroughly performed. In the present study, 70 % ethanolic and water extracts from three oak species (Quercus dentata, Q. serrata, and Q. aliena) showed antioxidant and anti-glycation potential. Thus, the components of the three oak species were profiled using ultra-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry. The analysis showed that phenolic acids, ellagitannins, ellagic acid, procyanidin, and flavonoid (quercetin, myricetin, kaempferol, isorhamnetin, and taxifolin) glycosides are the main phenolic compounds. Based on the fluorescence assay, they act as strong inhibitors of non-enzymatic advanced glycation end-products (AGEs) formation in the bovine serum albumin (BSA) and skin proteins (collagen and elastin). Furthermore, mass fragmentation analysis demonstrated that ellagitannin, procyanidin B1 and flavonoid glycosides effectively trapped methylglyoxal (MGO), a reactive carbonyl intermediate and an important precursor of AGEs, to generate mono-, di-, or tri-MGO. Collectively, ellagic acid, ellagitannins, procyanidin B1, and flavonoid glycosides, the main active ingredients of three oak species (Q. dentata, Q. serrata, and Q. aliena), may be employed as lead structures in the development of functional foods or drugs to prevent diseases caused by aging and excessive sugar consumption.

Abstract Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been recognized as promising cytotherapeutics due to their demonstrated immunomodulatory effects in various preclinical models. The immunomodulatory capabilities of EVs stem from the proteins and genetic materials they carry from parent cells, but the cargo contents of EVs are significantly influenced by MSC tissues and donors, cellular age and culture conditions, resulting in functional variations. However, there are no surrogate assays available to validate the immunomodulatory potency of MSC‐EVs before in vivo administration. In previous work, we discovered that microcarrier culture conditions enhance the immunomodulatory function of MSC‐EVs, as well as the levels of immunosuppressive molecules such as TGF‐β1 and let‐7b in MSC‐EVs. Building on these findings, we investigated whether TGF‐β1 levels in MSC‐EVs could serve as a surrogate biomarker for predicting their potency in vivo. Our studies revealed a strong correlation between TGF‐β1 and let‐7b levels in MSC‐EVs, as well as their capacity to suppress IFN‐γ secretion in stimulated splenocytes, establishing biopotency and surrogate assays for MSC‐EVs. Subsequently, we validated MSC‐EVs generated from monolayer cultures (ML‐EVs) or microcarrier cultures (MC‐EVs) using murine models of experimental autoimmune uveoretinitis (EAU) and additional in vitro assays reflecting the Mode of Action of MSC‐EVs in vivo. Our findings demonstrated that MC‐EVs carrying high levels of TGF‐β1 exhibited greater efficacy than ML‐EVs in halting disease progression in mice with EAU as well as inducing apoptosis and inhibiting the chemotaxis of retina‐reactive T cells. Additionally, MSC‐EVs suppressed the MAPK/ERK pathway in activated T cells, with treatment using TGF‐β1 or let‐7b showing similar effects on the MAPK/ERK pathway. Collectively, our data suggest that MSC‐EVs directly inhibit the infiltration of retina‐reactive T cells toward the eyes, thereby halting the disease progression in EAU mice, and their immunomodulatory potency in vivo can be predicted by their TGF‐β1 levels.

The fluorescent antibody to membrane antigen (FAMA) test is the gold standard for measuring the immunity induced by varicella vaccines with high sensitivity and specificity. However, certain aspects of the FAMA test, such as time consumption, non-automation, and subjective interpretation by observers using fluorescence microscopy, are obstacles to handling large amounts of samples. To overcome these hurdles, flow cytometry was adopted to analyze and compare the flow FAMA titer with the classic FAMA titer. In addition, to save time in FAMA antigen preparation and reduce lot-to-lot variation, the stability of the FAMA antigen stored in liquid nitrogen was investigated. The FAMA test was performed on sera from 229 children, and antibody titers were analyzed using fluorescence microscopy (classic FAMA) and flow cytometry (flow FAMA). For comparison, glycoprotein enzyme immunoassay (gpEIA) titer was also measured. A strong correlation was found between the flow and classic FAMA titers, and the flow FAMA and gpEIA titers, with Pearson's r of 0.9316 and 0.8588, respectively. Between the classic FAMA and gpEIA titers, the Pearson's r value was 0.8156. The positive percent agreement, negative percent agreement, and area under the curve of the flow FAMA against classic FAMA were 95.0 %, 86.8 %, and 0.909, respectively. And those of the flow FAMA against gpEIA were 80.0 %, 87.6 %, and 0.838, respectively. The FAMA antigen stored in liquid nitrogen was stable for up to 12 months. Based on the above data, flow FAMA has the potential to be used as an alternative to classic FAMA. Moreover, pre-made FAMA antigen may reduce the preparation time and lot-to-lot variation of FAMA test.

Adhesives with excellent adhesion and high elongation at cryogenic temperatures are necessary for fields such as aerospace, transportation, superconductors, and medicine, but have difficult requirements. This study aimed to develop a solvent-free, two-component polyurethane (PU) adhesive with excellent adhesion and high elongation, especially in ultra-low temperature conditions. we incorporated bulky polydimethylsiloxane (PDMS) diol into the hard segment of the PU adhesive to enhance flexibility and improve physical cross-linking within the adhesive matrix. The resulting PDMS-based PU adhesive showed a tensile strength of 120 MPa at −170 °C and a high elongation of approximately 4 %. It showed a lap-shear strength of up to 13 MPa at −196 °C. Additionally, the adhesive was curable at 23 °C. In this study, the cryogenic applicability of the PU adhesive was evaluated at −170 °C (103 K, liquid natural gas) and −196 °C (77 K, liquid nitrogen). Future research on the polymer adhesive materials applicable to ultra-low temperatures, such as 20 K, may be necessary if storage and transportation of liquid hydrogen become feasible.

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation.

Abstract Adapted immune cells are known to develop memory functions that increase resistance to subsequent infections after initial pathogen exposure, however, it is unclear whether non‐immune cells, like tissue‐resident stem cells, have similar memory functions. Here, it is found that tissue‐resident stem cells crucial for tissue regeneration show diminished adverse effects on diverse stem cell functions against successive exposure to foreign antigen (β‐glucan) to maintain tissue homeostasis and stability both in vitro and in vivo. These data suggest that endometrial stem cells may possess a robust memory function, in contrast, fully differentiated cells like fibroblasts and vesicular cells do not show these memory mechanisms upon consecutive antigen exposure. Moreover, the pivotal role of Angiopoietin‐like 4 (ANGPTL4) in regulating the memory functions of endometrial stem cells is identified through specific shRNA knockdown in vitro and knockout mice in vivo experiments. ANGPTL4 is associated with the alteration of diverse stem cell functions and epigenetic modifications, notably through histone H3 methylation changes and two pathways (i.e., PI3K/Akt and FAK/ERK1/2 signaling) upon consecutive antigen exposure. These findings imply the existence of inherent self‐defense mechanisms through which local stem cells can adapt and protect themselves from recurrent antigenic challenges, ultimately mitigating adverse consequences.

The Sogatella furcifera (Horváth) (Homoptera: Delphacidae) is a white-backed planthopper (WBPH) that causes “hopper burn” in rice, resulting in severe yield loss. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter that inhibits neurotransmission in insects by binding to specific receptors. In this study, we investigated the potential role of GABA in modulating rice resistance to WBPH and evaluated possible defense mechanisms. The experiment was conducted in green house in pots consist of four groups: control, GABA-treated, WBPH-infested, and WBPH-infested treated with GABA. Among the various tested concentration of GABA, 15 mM GABA was applied as a single treatment in water. The treatment was administered one week before WBPH infestation. The results revealed that 15 mM GABA treatment strongly increased WBPH resistance. A plate-based assay indicated that direct application of 15 mM GABA increased the mortality rate of WBPH and increased the damage recovery rate in rice plants. We found that GABA treatment increased the activation of antioxidant enzymes and reduced the reactive oxygen species content and malondialdehyde contents, and reduced the damage rate caused by WBPH. Interestingly, GABA-supplemented plants infested with WBPH exhibited increased phenylalanine ammonia-lyase and pathogenesis-related (PR) genes expression levels. GABA induced the accumulation of abscisic acid (ABA) and salicylic acid (SA) and enhanced the stomata closure and reduced leaf vessels to reduce water conductance during WBPH stress. Furthermore, we found that GABA application to the plant induced the expression of Jasmonic acid (JA) biosynthesis genes (LOX, AOS, AOC, and OPR) and melatonin biosynthesis-related genes (TDC, T5H, ASMT, and SNAT). Our study suggested that GABA increases resistance against WBPH infestation by regulating antioxidant defense system, TCA cycle regulation, phytohormonal signaling, and PR gene regulation.

Ongoing obstacles in preclinical drug testing have raised significant concerns within the pharmaceutical industry. Recently, utilizing the potential of three‐dimensional (3D) bioprinting offers a solution for creating tissue models for screening of the effectiveness and safety of new drugs. In this study, the anti‐inflammatory potential of garlic extracts is assessed, specifically N‐Benzyl‐N‐methyl‐dodecan‐1‐amine (BMDA), using a 3D bioprinted artificial skin model. Comprehensive physicochemical characterization and immunocytochemical analysis demonstrate that the 3D bioprinted skin model exhibits structures and functions resembling human skin. BMDA treatment in a prepared skin model reveals its capacity to mitigate H2O2‐induced oxidative stress and trigger anti‐inflammatory responses. Notably, BMDA reduces the expression of pro‐inflammatory cytokines and chemokines by downregulating NF‐κB and mitogen‐activated protein kinase inflammatory signaling pathways. In summary, our findings highlight the potential of an artificial skin model as a robust platform for the development of new drugs.

Abstract Transient global amnesia (TGA) often involves precipitating events associated with changes in autonomic nervous system (ANS), and heart rate variability (HRV) reflects the ANS state. This study aimed to investigate HRV changes after TGA. A retrospective analysis of HRV included patients diagnosed with TGA between January 2015 and May 2020. The time and frequency domains of HRV were compared among three groups: early (

Abstract Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (